Biological relapse in multiple myeloma: Outcome and treatment strategies in a Spanish real-world setting.

Recommendations regarding the best time to start treatment in patients with relapsed/refractory multiple myeloma (RRMM) after biological relapse/progression (BR) are unclear. This observational, prospective, multicenter registry aimed to evaluate the impact on time to progression (TTP) of treatment initiation at BR versus at symptomatic clinical relapse (ClinR) based on the Spanish routine practice in adult patients with RRMM. Patients had two or less previous treatment lines and at least one previous partial response. Baseline characteristics and treatment outcomes were recorded, and survival was analyzed. Of 225 patients, 110 were treated at BR (TxBR group) and 115 at ClinR (TxClinR group) according to the investigators' criteria. The proportion of patients with higher ECOG, previous noncomplete remission (CR), and second relapse were significantly higher in the TxBR group compared to the TxClinR group. TheTxClinR group showed improved outcomes, including TTP, compared to the TxBR group. Progression-free survival increased in the TxClinR group (56.2 months) compared to the TxBR group (32.5 months) (p = 0.0137), and median overall survival also increased (p = 0.0897). Median TTP was significantly longer in patients relapsing from a CR (50.4 months) and in their first relapse (38.7 months) compared to those relapsing from a non-CR response (32.9 months) and in their second relapse (25.2 months). Physicians seemed to start treatment earlier in RRMM patients with poor prognosis features. Previous responses to anti-MM treatment and the number of prior treatment lines were identified as prognosis factors, whereby relapse from CR and first relapse were associated with a longer time to progression.

A RAB7A phosphoswitch coordinates Rubicon Homology protein regulation of Parkin-dependent mitophagy.

Activation of PINK1 and Parkin in response to mitochondrial damage initiates a response that includes phosphorylation of RAB7A at Ser72. Rubicon is a RAB7A binding negative regulator of autophagy. The structure of the Rubicon:RAB7A complex suggests that phosphorylation of RAB7A at Ser72 would block Rubicon binding. Indeed, in vitro phosphorylation of RAB7A by TBK1 abrogates Rubicon:RAB7A binding. Pacer, a positive regulator of autophagy, has an RH domain with a basic triad predicted to bind an introduced phosphate. Consistent with this, Pacer-RH binds to phosho-RAB7A but not to unphosphorylated RAB7A. In cells, mitochondrial depolarization reduces Rubicon:RAB7A colocalization whilst recruiting Pacer to phospho-RAB7A-positive puncta. Pacer knockout reduces Parkin mitophagy with little effect on bulk autophagy or Parkin-independent mitophagy. Rescue of Parkin-dependent mitophagy requires the intact pRAB7A phosphate-binding basic triad of Pacer. Together these structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation.

Effects of different insulin sensitisers in the management of polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin sensitivity, insulin sensitisers have been used in PCOS. However, direct comparisons across these agents are limited. This study compared the effects of metformin, rosiglitazone and pioglitazone in the management of PCOS to inform the 2023 International Evidence-based PCOS Guideline. DESIGN: Systematic review and meta-analysis of the literature. PATIENTS: Women with PCOS and treatment with insulin sensitisers. MEASUREMENTS: Hormonal and clinical outcomes, as well as side effects. RESULTS: Of 1660 publications identified, 13 randomised controlled trials were included. Metformin was superior in lowering weight (mean difference [MD]: -4.39, 95% confidence interval [CI]: -7.69 to -1.08 kg), body mass index (MD: -0.95, 95% CI: -1.41 to -0.49 kg/m2 ) and testosterone (MD: -0.10, 95% CI: -0.18 to -0.03 nmol/L) versus rosiglitazone, whereas there was no difference when comparing metformin to pioglitazone. Adding rosiglitazone or pioglitazone to metformin did not improve metabolic outcomes. However, rosiglitazone seemed superior to metformin in lowering lipid concentrations. CONCLUSIONS: Metformin should remain the first-line insulin sensitising treatment in adults with PCOS for the prevention and management of weight and metabolic features. The addition of thiazolidinediones appears to offer little benefit.

Analysis of 12 X-STRs loci in a population from southeastern Brazil.

Short tandem repeat (STR) markers on the X chromosome have a high potential for solving complex kinship analysis and individual identification cases. To achieve such purposes, allele and haplotype frequencies for the specific population are necessary. Nonetheless, such frequencies are not always available. Therefore, we obtained haplotypes from 520 unrelated males from four different geographic regions of Espírito Santo - Brazil, using the Investigator Argus X-12 kit. Forensic parameters for linked groups of four X-STR loci are reported. Genetic distance analyzes suggest that ES population is genetically closer to the Italian population and farther from the Mexican one, among the populations analyzed in this study.

Effects of an antenatal dietary intervention in women with obesity or overweight on child outcomes at 8-10 years of age: LIMIT randomised trial follow-up.

BACKGROUND: The LIMIT randomised controlled trial looked at the effect of a dietary and lifestyle intervention compared with routine antenatal care for pregnant women with overweight and obesity on pregnancy outcomes. While women in the intervention group improved diet and physical activity with a reduction of high birth weight, other outcomes were similar. We have followed the children born to women in this study at birth, 6 and 18 months and 3-5 years of age and now report follow-up of children at 8-10 years of age. METHODS: Children at 8-10 years of age who were born to women who participated in the LIMIT randomised trial, and whose mother provided consent to ongoing follow-up were eligible for inclusion. The primary study endpoint was the incidence of child BMI z-score > 85th centile for child sex and age. Secondary study outcomes included a range of anthropometric measures, neurodevelopment, child dietary intake, and physical activity. Analyses used intention to treat principles according to the treatment group allocated in pregnancy. Outcome assessors were blinded to the allocated treatment group. RESULTS: We assessed 1,015 (Lifestyle Advice n = 510; Standard Care n = 505) (48%) of the 2,121 eligible children. BMI z-score > 85th percentile was similar for children of women in the dietary Lifestyle Advice Group compared with children of women in the Standard Care Group (Lifestyle Advice 479 (45%) versus Standard Care 507 (48%); adjusted RR (aRR) 0.93; 95% CI 0.82 to 1.06; p = 0.302) as were secondary outcomes. We observed that more than 45% of all the children had a BMI z-score > 85th percentile, consistent with findings from follow-up at earlier time-points, indicating an ongoing risk of overweight and obesity. CONCLUSIONS: Dietary and lifestyle advice for women with overweight and obesity in pregnancy has not reduced the risk of childhood obesity, with children remaining at risk of adolescent and adult obesity. Other strategies are needed to address the risk of overweight and obesity in children including investigation of preconception interventions to assess whether this can modify the effects of maternal pre-pregnancy BMI. The LIMIT randomised controlled trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).

Type 1 diabetes, periodontal health, and a familial history of hyperlipidaemia is associated with oral microbiota in children: a cross-sectional study.

BACKGROUND: Hyperlipidaemia may play a significant role in the interrelationship between type 1 diabetes (T1D) and periodontal disease. A potential mechanism that links these three aspects together is the oral microbiota. We wanted to determine if there is an association between hyperlipidaemia, periodontal disease, and the oral microbiota of children with T1D, as this has not yet been explored. METHODS: In a post-hoc, cross-sectional study using 16S rRNA gene sequencing, we explored links between oral bacterial diversity and composition of gingival swab samples from 72 children with T1D to periodontal risk factors and hyperlipidaemia status of first-degree relatives. While multiple periodontal risk factors were assessed, we used periodontal pocket depth of 3 mm to characterise periodontal risk. As periodontal pocket depth confounded the analysis of familial history of hyperlipidaemia, a multivariate analyses were performed (i.e., no periodontal risk markers in children with or without a family history of hyperlipidaemia were compared to counterparts who did not have periodontal risk markers) to examine linkages between these factors and diversity and composition of the microbiome. RESULTS: In participants with no periodontitis risk, children with a family history of dyslipidemia had different bacterial diversity and composition compared to those without a familar hisitory. In contrast, such differences did not exist in the children with periodontal risk, whether or not they had a family history of hyperlipidaemia. Co-occurrence networks showed that these differences in children with no periodontists risk were linked to the presence of fewer oral microbial networks, but more microbes linked to mature plaque structures. In contrast, children with periodontal risk markers, regardless of family history of hyperlipidaemia, contained co-occurrence networks that were associated with microbes linked to periodontal disease. CONCLUSIONS: In children diagnosed with T1D, our findings support an association between oral microbiota and two different exposure variables: familial history of hyperlipidaemia and periodontal risk factors.

ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 diabetes in children and adolescents.

Since the 2018 ISPAD guidelines on this topic, follow-up of large cohorts from around the globe have continued informing the current incidence and prevalence of co-morbidities and complications in young adults with youth-onset type 2 diabetes (T2D). This chapter focuses on the risk factors, diagnosis and presentation of youth-onset T2D, the initial and subsequent management of youth-onset T2D, and management of co-morbidities and complications. We include key updates from the observational phase of the multi-center Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial, the SEARCH for Diabetes in Youth (SEARCH) study and new data from the Restoring Insulin Secretion (RISE) study, a head-to-head comparison of youth onset vs adult-onset T2D. We also include an expanded section on risk factors associated with T2D, algorithms and tables for treatment, management, and assessment of co-morbidities and complications, and sections on recently approved pharmacologic therapies for the treatment of youth-onset T2D, social determinants of health, and settings of care given COVID-19 pandemic.

Polycystic Ovary Syndrome in Adolescence.

Polycystic ovary syndrome (PCOS) is a common, complex, and chronic condition that presents many diagnostic and management challenges for managing clinicians. PCOS diagnosis in adolescents presents a particular challenge for treating clinicians due to the overlap of diagnostic features with normal physiological changes during adolescence. Adolescent diagnostic criteria include well-defined menstrual irregularity according to time postmenarche and hyperandrogenism, but does not require the use of pelvic ultrasound. Adolescents with only one criterion should be considered at risk of PCOS and be followed up around transition to adult care. While PCOS was traditionally considered to be a reproductive disorder, PCOS is now recognized to have major metabolic and cardiovascular health consequences and psychological sequelae that can be present from adolescence. Management of PCOS includes healthy lifestyle, metformin, combined oral contraceptive pill, and/or antiandrogens according to symptoms of concern even in adolescents at risk of PCOS.

Criteria for Diagnosis of Polycystic Ovary Syndrome during Adolescence: Literature Review.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine conditions in women. PCOS may be more challenging to diagnose during adolescence due to an overlap with the physiological events of puberty, which are part of the diagnostic criteria in adult women. This review focuses on the evidence available in relation to PCOS diagnostic criteria for adolescents. Adolescent PCOS should be diagnosed using two main criteria irregular -menstrual cycles (relative to number of years post-menarche) and hyperandrogenism (clinical and/or biochemical); after excluding other conditions that mimic PCOS. Accurate definitions of the two main criteria will decrease challenges/controversies with the diagnosis and provide timely diagnosis during adolescence to establish early management. Despite the attempts to create accurate diagnostic criteria and definitions, this review highlights the limited research in this area, especially in the follow up of adolescents presenting with one diagnostic feature that are called "at risk of PCOS". Studies in adolescents continue to use the Rotterdam diagnostic criteria that uses pelvic ultrasound. This is inappropriate, because previous and emerging data that show many healthy adolescents have polycystic ovarian morphology in the early years post-menarche. In the future, anti-Müllerian hormone levels might help support PCOS diagnosis if adolescents meet two main criteria.

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

Regional changes of brain structure during progression of idiopathic Parkinson's disease - A longitudinal study using deformation based morphometry.

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder with a broad spectrum of motor and non-motor symptoms. The neuropathological characteristics of idiopathic PD are the degeneration of dopaminergic neurons in the striatum, and the propagation of aggregates of misfolded α-synuclein in the brain following a specific pattern (Braak et al., 2006). The relationship of this pattern with motor and cognitive symptoms is still equivocal. Therefore, we investigated longitudinally the spatio-temporal patterns of atrophy propagation in PD, their inter-individual variability and associations with clinical symptoms. Magnetic resonance (MR) images of 37 PD patients and 27 controls were acquired at up to 15 time-points per subject, and over observation periods of up to 8.8 years (mean: 3.7 years). MR images were analyzed by Deformation-based Morphometry to measure region volumes and their longitudinal changes. Differences of these regional volume data between patients and controls and their associations with clinical symptoms were calculated. At baseline, group differences in the regional volumes were found mainly in areas of the sensory, motor and orbitofrontal cortices, areas in the frontal operculum, inferior frontal sulcus, hippocampus and entorhinal cortex, and in the substantia nigra, among others. The longitudinal analysis yielded more widespread and more pronounced group differences, with significantly accelerated volume decreases in PD patients in the occipital and temporal lobes, the inferior parietal lobule, as well as in the insula, putamen and nucleus basalis Meynert. The white matter was less affected than the gray matter. Worse clinical scores (MMSE, PDQ-39, UPDRS-III) were in particular associated with volume decreases of cortical areas, amygdala and basal forebrain nuclei, but not of the basal ganglia. The observed longitudinal patterns of accelerated volume decrease in PD patients largely coincide with the pattern of α-synuclein pathology in PD stages 3-5 as proposed by Braak and colleagues. Thus, longitudinal DBM appears to depict already in-vivo the progression of neuropathological changes.

Proteolytic activation of anti-Müllerian hormone is suppressed in adolescent girls.

PURPOSE: The ratio of the anti-Müllerian hormone (AMH) precursor (proAMH) to active AMH (AMHN,C) is higher in childhood than in adulthood but has never been quantified during adolescence. The ratio of proAMH to total AMH (AMH prohormone index, API) was examined during the puberty in healthy girls. The API was also compared between girls with and without polycystic ovary syndrome (PCOS) to determine if there were differences that could assist in PCOS diagnosis during adolescence. METHODS: Total AMH and proAMH were measured by immunoassay in a single-centre, cross-sectional observational study; 61 controls and 29 girls with PCOS were included in the study (age range 8-21 years). The API was calculated as proAMH as a percentage of total AMH. Differences in API between control and PCOS subjects and across age-groups were examined by Welch's ANOVA. The relationship between API and a range of metabolic parameters was examined by Pearson correlation. RESULTS: The API in healthy females increased between the ages of 10~15 years and declined from 15~20 years (p < 0.001). The API was negatively correlated with body mass index in the control (p = 0.04) and PCOS groups (p = 0.007). The API was associated with factors related to adiposity and lipid metabolism. The API was not significantly different in control girls and girls with PCOS. CONCLUSIONS: Higher API during adolescence suggests that proteolytic activation of proAMH is suppressed during this life stage. API was not different between control girls and girls with PCOS indicating that it is not useful in diagnosis of PCOS during adolescence.

Diagnosis experiences of adolescents with polycystic ovary syndrome: Cross-sectional study.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) report delayed diagnosis of the condition and receiving inadequate information at diagnosis. No studies have investigated the diagnosis experiences of adolescents with PCOS. Our objective was to investigate the adolescents' experiences of PCOS diagnosis and their concerns about the condition. DESIGN: Cross-sectional study. PATIENT(S): Eighty-six adolescents (aged 13-19 years) were diagnosed with PCOS by a medical practitioner. Adolescents were recruited consecutively from paediatric and women's outpatient hospital clinics in South Australia and online PCOS support organisations in Australia and the United Kingdom (May 2017-June 2019). MEASUREMENTS: PCOS diagnosis experience and information received at the time of diagnosis were evaluated using a validated questionnaire. RESULTS: The majority of the adolescents (n = 67, 78%) were diagnosed with PCOS in less than 1 year from their first doctor's visit but 11 (13%) were diagnosed more than 2 years from that visit. Fifty-three adolescents (66%) saw 1-2 health professionals before the diagnosis was made. Forty-nine adolescents (57%) were satisfied with the overall diagnosis experience but adolescents were either dissatisfied or reported that the information was not mentioned after diagnosis in relation to lifestyle management (n = 47, 55%), long-term complications (n = 53, 62%) and emotional support and counselling (n = 65, 76%). CONCLUSIONS: The majority of adolescent girls with PCOS are receiving a timely diagnosis, but delayed diagnosis still occurs in a minority of adolescents. Current information provided at diagnosis is not meeting the needs of adolescents and is a lost opportunity for preventive healthcare at a critical transition to adult care period.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Long-term HbA1c in 7,961 Children and Young Adults in the Australasian Diabetes Data Network.

OBJECTIVE: The relationship between diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes and long-term glycemic control varies between studies. We aimed, firstly, to characterize the association of DKA and its severity with long-term HbA1c in a large contemporary cohort, and secondly, to identify other independent determinants of long-term HbA1c. RESEARCH DESIGN AND METHODS: Participants were 7,961 children and young adults diagnosed with type 1 diabetes by age 30 years from 2000 to 2019 and followed prospectively in the Australasian Diabetes Data Network (ADDN) until 31 December 2020. Linear mixed-effect models related variables to HbA1c. RESULTS: DKA at diagnosis was present in 2,647 participants (33.2%). Over a median 5.6 (interquartile range 3.2, 9.4) years of follow-up, participants with severe, but not moderate or mild, DKA at diagnosis had a higher mean HbA1c (+0.23%, 95% CI 0.11,0.28; [+2.5 mmol/mol, 95% CI 1.4,3.6]; P < 0.001) compared with those without DKA. Use of continuous subcutaneous insulin infusion (CSII) was independently associated with a lower HbA1c (-0.28%, 95% CI -0.31, -0.25; [-3.1 mmol/mol, 95% CI -3.4, -2.8]; P < 0.001) than multiple daily injections, and CSII use interacted with severe DKA to lower predicted HbA1c. Indigenous status was associated with higher HbA1c (+1.37%, 95% CI 1.15, 1.59; [+15.0 mmol/mol, 95% CI 12.6, 17.4]; P < 0.001), as was residing in postcodes of lower socioeconomic status (most vs. least disadvantaged quintile +0.43%, 95% CI 0.34, 0.52; [+4.7 mmol/mol, 95% CI 3.4, 5.6]; P < 0.001). CONCLUSIONS: Severe, but not mild or moderate, DKA at diagnosis was associated with a marginally higher HbA1c over time, an effect that was modified by use of CSII. Indigenous status and lower socioeconomic status were independently associated with higher long-term HbA1c.

A Systematic Scoping Review on Pedagogical Strategies of Interprofessional Communication for Physicians in Emergency Medicine.

BACKGROUND: Interprofessional communication (IPC) is integral to interprofessional teams working in the emergency medicine (EM) setting. Yet, the coronavirus disease 2019 pandemic has laid bare gaps in IPC knowledge, skills and attitudes. These experiences underscore the need to review how IPC is taught in EM. PURPOSE: A systematic scoping review is proposed to scrutinize accounts of IPC programs in EM. METHODS: Krishna's Systematic Evidence-Based Approach (SEBA) is adopted to guide this systematic scoping review. Independent searches of ninedatabases (PubMed, Embase, CINAHL, Scopus, PsycINFO, ERIC, JSTOR, Google Scholar and OpenGrey) and "negotiated consensual validation" were used to identify articles published between January 1, 2000 and December 31, 2020. Three research teams reviewed the data using concurrent content and thematic analysis and independently summarized the included articles. The findings were scrutinized using SEBA's jigsaw perspective and funneling approach to provide a more holistic picture of the data. IN TOTAL: 18,809 titles and abstracts were identified after removal of duplicates, 76 full-text articles reviewed, and 19 full-text articles were analyzed. In total, four themes and categories were identified, namely: (a) indications and outcomes, (2) curriculum and assessment methods, (3) barriers, and (4) enablers. CONCLUSION: IPC training in EM should be longitudinal, competency- and stage-based, underlining the need for effective oversight by the host organization. It also suggests a role for portfolios and the importance of continuing support for physicians in EM as they hone their IPC skills. HIGHLIGHTS: • IPC training in EM is competency-based and organized around stages.• IPC competencies build on prevailing knowledge and skills.• Longitudinal support and holistic oversight necessitates a central role for the host organization.• Longitudinal, robust, and adaptable assessment tools in the EM setting are necessary and may be supplemented by portfolio use.

Dysbiotic stress increases the sensitivity of the tumor vasculature to radiotherapy and c-Met inhibitors.

Antibiotic-induced microbial imbalance, or dysbiosis, has systemic and long-lasting effects on the host and response to cancer therapies. However, the effects on tumor endothelial cells are largely unknown. Therefore, the goal of the current study was to generate matched B16-F10 melanoma associated endothelial cell lines isolated from mice with and without antibiotic-induced dysbiosis. After validating endothelial cell markers on a genomic and proteomic level, functional angiogenesis assays (i.e., migration and tube formation) also confirmed their vasculature origin. Subsequently, we found that tumor endothelial cells derived from dysbiotic mice (TEC-Dys) were more sensitive to ionizing radiotherapy in the range of clinically-relevant hypofractionated doses, as compared to tumor endothelial cells derived from orthobiotic mice (TEC-Ortho). In order to identify tumor vasculature-associated drug targets during dysbiosis, we used tandem mass tag mass spectroscopy and focused on the statistically significant cellular membrane proteins overexpressed in TEC-Dys. By these criteria c-Met was the most differentially expressed protein, which was validated histologically by comparing tumors with or without dysbiosis. Moreover, in vitro, c-Met inhibitors Foretinib, Crizotinib and Cabozantinib were significantly more effective against TEC-Dys than TEC-Ortho. In vivo, Foretinib inhibited tumor growth to a greater extent during dysbiosis as compared to orthobiotic conditions. Thus, we surmise that tumor response in dysbiotic patients may be greatly improved by targeting dysbiosis-induced pathways, such as c-Met, distinct from the many targets suppressed due to dysbiosis.

Early markers of periodontal disease and altered oral microbiota are associated with glycemic control in children with type 1 diabetes.

OBJECTIVES: To determine the relationship between periodontal disease and glycemic control in children with type 1 diabetes and to characterize the diversity and composition of their oral microbiota. METHODS: Cross-sectional study including children with type 1 diabetes recruited from clinics at the Women's and Children's Hospital (Australia). Participants had a comprehensive dental assessment, periodontal examination, and buccal and gingival samples collected for 16S rRNA sequencing. RESULTS: Seventy-seven participants (age 13.3 ± 2.6 years, 38 males, BMI z-score 0.81 ± 0.75) had a diabetes duration of 5.6 ± 3.9 years and median HbA1c of 8.5% (range 5.8-13.3), 69.4 mmol/mol (range 39.9-121.9). Thirty-eight (49%) had early markers of periodontal disease. HbA1c was positively correlated with plaque index (Rho = 0.34, P = 0.002), gingival index (Rho = 0.30, P = 0.009), bleeding on probing (Rho = 0.44, P = 0.0001) and periodontal pocket depth >3 mm (Rho = 0.21, P = 0.06). A 1% increase in HbA1c was independently associated with an average increase in bleeding on probing of 25% (P = 0.002) and with an increase in the rate of sites with pocket depth >3 mm of 54% (P = 0.003). Higher HbA1c was independently related to increased phylogenetic alpha diversity (P = 0.008) and increased compositional variation (beta diversity P = 0.02) in gingival, but not buccal, microbiota. Brushing frequency, plaque index, and gingival index had a significant effect on microbiota composition, independent of HbA1c. CONCLUSIONS: Children with type 1 diabetes showed a continuous relationship between less favorable glycemic control and increased early markers of periodontal disease. Glycemic control was also related to the complexity and richness of the plaque microbiota, with diversity increasing as HbA1c levels increase.

Investigating the 1-year decline in midbrain-to-pons ratio in the differential diagnosis of PSP and IPD.

BACKGROUND: A reliable measure of PSP-specific midbrain atrophy, the midbrain-to-pons ratio (MTPR) has been reported to support the differential diagnosis of progressive supranuclear palsy (PSP) from idiopathic Parkinson's disease (IPD). Since longitudinal analyses are lacking so far, the present study aimed to evaluate the diagnostic value of the relative change of MTPR (relΔt_MTPR) over a 1-year period in patients with PSP, IPD, and healthy controls (HC). METHODS: Midsagittal individual MRIs of patients with PSP (n = 15), IPD (n = 15), and healthy controls (HC; n = 15) were assessed and the MTPR at baseline and after 1 year were defined. The diagnostic accuracy of the MTPR and its relative change were evaluated using ROC curve analyses. RESULTS: PSP-patients had a significantly lower MTPR at baseline (M = 0.45 ± 0.06), compared to both non-PSP groups (F (2, 41) = 62.82, p < 0.001), with an overall predictive accuracy of 95.6% for an MTPR ≤ 0.54. PSP-patients also presented a significantly stronger 1-year decline in MTPR compared to IPD (p < 0.001). Though predictive accuracy of relΔt_MTPR for PSP (M = - 4.74% ± 4.48) from IPD (M = + 1.29 ± 3.77) was good (76.6%), ROC analysis did not reveal a significant improvement of diagnostic accuracy by combining the MTPR and relΔt_MTPR (p = 0.670). Still, specificity for PSP increased, though not significantly (p = 0.500). CONCLUSION: The present results indicate that the relΔt_MTPR is a potentially useful tool to support the differential diagnosis of PSP from IPD. For its relative 1-year change, still, more evaluation is needed.

Role of meditation to improve children's health: Time to look at other strategies.

In the United States, it is reported that up to 7 million of the population practice some form of meditation with the main purpose of improving emotional wellbeing and reducing stress. As the prevalence of mental health conditions continues to climb, other forms of health management strategies, including meditation practices, are increasingly used in adults. The evidence continues to emerge for the use of meditation as a way of managing health conditions in adults as demonstrated in systematic reviews and randomised controlled trials. There is also growing evidence evaluating the use of meditation practices and their potential benefits for child and adolescent health. Studies have identified improvements in mood and mental health conditions, school attendance and attention in the classroom in children and adolescents. This article aims to provide a perspective on commonly evaluated meditation types, such as Transcendental Meditation and mindfulness-based stress reduction. The article also aims to discuss the available evidence for the use of meditation to improve health and general wellbeing of children, including the use of meditation programs in schools, the current downfalls and limitations to the existing literature around meditation, and important points that healthcare practitioners need to consider when discussing the use of meditation as an additional strategy to manage and improve health and wellbeing in children and adolescents.

Quality of life in adolescent girls with polycystic ovary syndrome.

Quality of life (QoL) is an important aspect of health and well-being. QoL is reduced in women with polycystic ovary syndrome (PCOS), but there is limited data in adolescents. This review aimed to assess studies regarding the QoL of adolescent girls with PCOS. Five databases were searched for relevant studies. Studies were included if they were conducted in adolescent girls with PCOS, aged 12-22 years old, and used a questionnaire to measure QoL. The search identified a total of 254 studies, and after exclusions, 11 relevant studies were included in the review. Most studies had a relatively small sample size, but overall included a total of 512 adolescents with PCOS. In most cases, adolescent girls with PCOS have reduced QoL when compared to healthy girls, and PCOS symptoms/excess weight impact on their QoL. Further research is required due to limited data on QoL in adolescents with PCOS of normal weight.