Familial resemblance and diversity in bone mass and strength in the population are established during the first year of postnatal life

Familial resemblance and diversity in bone structure and strength in adulthood are determined in part during growth. Whether these characteristics are established during gestation or shortly after birth is not known. Total‐body, lumbar spine, and femoral neck size and mass and indices of tibial bending strength and distal radial compressive strength were measured using bone densitometry and quantitative computed tomography in 236 girls at 18.5 years of age. Among them, 219, 141, and 105 girls had crown‐heel length (CHL) and weight recorded at birth and at 6 and 12 months of age, and then height and weight were recorded at 3, 5, 10, 13, and 15 years of age in 181, 176, 127, 111, and 228 girls, respectively. Of these girls, 101 and 93 girls also had bone structure assessed at 11 and 13 years of age, respectively. Similar bone measurements were made once in 78 mother‐father pairs. CHL and weight at birth did not correlate or did so weakly with bone traits in girls at 18 years of age. By contrast, CHL at 6 months correlated with the height, bone traits, and strength at puberty and at 18 years of age (r = 0.24–0.56, p < .001) in girls and with their parents' height and bone traits (r = 0.15–0.37, p < .05). When the girls' CHL at 6 months was stratified into quartiles, the absolute and relative differences in bone traits observed at puberty (～11.5 years) were maintained as these traits tracked during the ensuing 7 years. Similarly, weight at 6 months correlated with the girls' bone traits at puberty and 18 years of age (r = 0.22–0.55, p < .05). During puberty and at 18 years of age, the girls' bone traits correlated with the corresponding traits in their parents (r = 0.32–0.43, p < .01). It is concluded that familial resemblance in bone structural strength and the position of an individual's bone traits relative to others in adulthood are likely to be established during the first year of life. Thus susceptibility to bone fragility late in life has its antecedents established early in life. © 2010 American Society for Bone and Mineral Research     

Cephalometric pharyngeal changes after Le Fort I osteotomy in different types of clefts

Fifty patients with clefts (30 unilateral cleft lip and palate (UCLP), 9 bilateral cleft lip and palate (BCLP), and 11 cleft palate only (CP), mean age 25 years) treated with Le Fort I osteotomy were compared retrospectively from cephalograms taken shortly before operation, and at six months and one year postoperatively. Patients with bimaxillary surgery or previous velopharyngoplasty, or both, were excluded. Maxillary advancement was moderate in all groups. One year postoperatively there was a significant change (73%–90% of the surgical advancement) in the sagittal depth of the nasopharyngeal airway but not in the depth of the oropharyngeal airway, the length of the soft palate or the position of the hyoid bone. The nasopharyngeal airway was largest in the CP group both preoperatively and postoperatively. Eleven patients (7 CP, 4 UCLP) had a velopharyngoplasty after the osteotomy to improve their speech. There was no difference in the nasopharyngeal airway in the patients treated by velopharyngoplasty compared with those not so treated, but they seemed to have the shortest maxillas and the greatest surgical changes vertically.     

Recent advances in optical diagnosis of oral cancers: Review and future perspectives

Optical diagnosis techniques offer several advantages over traditional approaches, including objectivity, speed, and cost, and these label‐free, noninvasive methods have the potential to change the future workflow of cancer management. The oral cavity is particularly accessible and, thus, such methods may serve as alternate/adjunct tools to traditional methods. Recently, in vivo human clinical studies have been initiated with a view to clinical translation of such technologies. A comprehensive review of optical methods in oral cancer diagnosis is presented. After an introduction to the epidemiology and etiological factors associated with oral cancers currently used, diagnostic methods and their limitations are presented. A thorough review of fluorescence, infrared absorption, and Raman spectroscopic methods in oral cancer diagnosis is presented. The applicability of minimally invasive methods based on serum/saliva is also discussed. The review concludes with a discussion on future demands and scope of developments from a clinical point of view. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2403–E2411, 2016     

The Association Between Visual Acuity and Functional Limitations: Findings from a Nationally Representative Population Survey

Purpose: To determine the independent effect of visual acuity on individual activities of daily living (ADL), instrumental activities of daily living (IADL) and mobility. Methods: Cross-sectional survey on a sample representing the Finnish population aged 55 years and above. Of the 3392 eligible people, 3185 (93.9%) were interviewed, 2870 (84.6%) attended a comprehensive health examination, and 2781 (82.0%) had distance visual acuity (VA) assessed. A home interview included assessment of ADL, IADL and mobility, demographic variables and chronic conditions. Mobility measurements and binocular VA were assessed during the examination. Results: Prevalence of ADL, IADL, and mobility limitations increased with decreasing VA (p < 0.001). Visually impaired persons (VA ≤ 0.25) had ADL disabilities four times more likely than those with good VA (VA ≥ 0.8) after adjustment for socio-demographic and behavioral factors, and chronic conditions (OR 4.36, 95%CI 2.44–7.78). Limitations in IADL and measured mobility were five times as likely (OR 4.82, 95%CI 2.38–9.76 and OR 5.37, 95%CI 2.44–7.78, respectively), and self-reported mobility limitations were three times as likely (OR 3.07, 95%CI 1.67–9.63) as in persons with good VA. Conclusions: Decreased VA is strongly associated with functional limitations, and even a slight decrease in VA was found to be associated with limitations in functioning.     

Characteristics of suicide among diabetes patients: A population based study of suicide victims in Northern Finland

ObjectiveRecent case reports of insulin suicides have raised the need to study in detail the suicides among diabetes patients.MethodsThe data consisted of 2489 suicides (2030 men, 459 women) in Northern Finland during 1988 to 2010. The suicide victims with hospital-treated type 1 (n = 27) or type 2 diabetes (n = 51) were compared with those without diabetes (n = 2411).ResultsOf all suicide victims, 3.1% had diabetes (34.6% type 1 and 65.4% type 2 diabetes). 24.0% of victims with type 2 diabetes were under the influence of alcohol when they died from suicide, while the proportion was 44.4% in type 1 diabetes and 46.6% in victims without diabetes (P = 0.007). Compared to those with type 2 diabetes or without diabetes, victims with type 1 diabetes had suffered more commonly from depression (44.4%, 23.5%, 19.9%, respectively) (P = 0.006) and chosen self-poisoning as suicide method (48.1%, 31.4%, and 18.0%) (P < 0.001). In victims with type 1 diabetes insulin as a suicide method covered half of the self-poisoning cases, while the proportion in type 2 diabetes was 13%.ConclusionWe suggest that physicians who treat diabetes patients should evaluate co-occurring depression and substance abuse, both of which are major risk factors of suicide.     

Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008

Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10⁻⁸). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10⁻⁶) and TAP2 (P = 1·59 × 10⁻⁵). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.     

Deletions spanning the neurofibromatosis type 1 gene: Implications for genotype-phenotype correlations in neurofibromatosis type 1?

Neurofibromatosis type 1 (NF1) is an autosomal-dominant disorder characterized by abnormalities of tissues predominantly derived from the neural crest. Symptoms are highly variable and severity cannot be predicted, even within families. DNA of 84 unrelated patients with NF1, unselected for clinical features or severity, were screened with intragenic polymorphic repeat markers and by Southern analysis with cDNA probes. Deletions of the entire gene were detected in five patients from four unrelated families. Their phenotype resembled that of five previously reported patients with deletions, including intellectual impairment and dysmorphic features, but without an excessive number of dermal neurofibromas. This report supports the hypothesis that large deletions spanning the entire NF1 gene may lead to a specific phenotype. Hum Mutat 9:458–464, 1997 © 1997 Wiley-Liss, Inc.     

Evaluation of the thermal insulation of clothing of infants sleeping outdoors in Northern winter

It is a common practice in Northern countries that children aged about 2 weeks to 2 years take their daytime sleep outdoors in prams in winter. The aim was to evaluate the thermal insulation of clothing of infants sleeping outdoors in winter. Clothing data of infants aged 3.5 months was collected, and sleep duration, skin and microclimate temperatures, humidity inside middle wear, air temperature and velocity of the outdoor environment were recorded during sleep taken outdoors (n = 34) and indoors (n = 33) in families’ homes. The insulation of clothing ensembles was measured by using a baby-size thermal manikin, and the values were used for defining clothing insulation of the observed infants. Required clothing insulation for each condition was estimated according to ISO 11079. Clothing insulation did not correlate with ambient air temperature. The observed and required insulation of the study group was equal at about −5°C, but overdressing existed in warmer and deficiency in thermal insulation in colder temperatures (r _s 0.739, p < 0.001). However, even at −5°C a slow cooling (ca. 0.012°C/min) of mean skin temperature (T _sk) was observed. When the difference between observed and required insulation increased, the cooling rate of T _sk increased linearly (r _s 0.605, p < 0.001) and the infants slept for a shorter period (r _s 0.524, p = 0.001). The results of this study show the difficulty of adjusting systematically the optimal thermal insulation for outdoor sleeping infants during northern winter. Therefore, the necessity for guidelines is obvious. The study provides information for adequate cold protection of infants sleeping in cold conditions.     

Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In order to determine whether the endogenous production of steroids is altered in the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar disorder (BPD), quantitative real‐time PCR was performed to detect mRNA expression level of key enzymes in the steroid biosynthetic pathways. In MDD, a significant decrease in mRNA level of cytochrome P450 17A1 (CYP17A1, synthesizing C19 ketosteroids) in the ACC and a significant increase in mRNA levels of hydroxysteroid sulfotransferase 2A1 [SULT2A1, catalyzing the sulfate conjugation of dehydroepiandrosterone (DHEA)] were observed in the DLPFC, suggesting alterations in DHEA and its sulfate metabolite DHEAS levels. Decreased intensity and distribution of CYP17A1 immunohistochemical staining was found in the ACC of MDD patients. Interestingly, there was a significant positive correlation between the mRNA levels of CYP17A1 and tyrosine‐related kinase B (TrkB) full length isoform. In a unique post‐mortem human brain slice culture paradigm, BDNF mRNA expression was found to be significantly increased following incubation with DHEA. Together, these data indicate a close relationship between DHEA and BDNF‐TrkB pathways in depression. Furthermore, in the DLPFC, higher mRNA levels of 11β‐hydroxysteroid dehydrogenase‐1 (HSD11B1, reducing cortisone to the active hormone cortisol) and steroidogenic acute regulatory protein (STAR, facilitating the shuttle of cholesterol through the intermembrane space) were found in the MDD patients and BPD patients, respectively. In conclusion, this study suggests the presence of a disturbance in the endogenous synthesis of DHEA and DHEAS in mood disorders, which has a close relationship with BDNF‐TrkB signaling.