Craniofacial morphology and growth in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis.

OBJECTIVES: To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial proportions of a Dutch control group. MATERIAL AND METHODS: We included seventy-four patients (43 patients with Muenke syndrome, 22 patients with Saethre-Chotzen syndrome, and 9 patients with TCF12-related craniosynostosis) who were referred between 1990 and 2020 (age range 4.84 to 16.83 years) and were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands. The control group consisted of 208 healthy children. RESULTS: Cephalometric values comprising the midface were decreased in Muenke syndrome (ANB: ß = -1.87, p = 0.001; and PC1: p < 0,001), Saethre-Chotzen syndrome (ANB: ß = -1.76, p = 0.001; and PC1: p < 0.001), and TCF12-related craniosynostosis (ANB: ß = -1.70, p = 0.015; and PC1: p < 0.033). CONCLUSIONS: In this study, we showed that the midface is hypoplastic in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis compared to the Dutch control group. Furthermore, the rotation of the maxilla and the typical craniofacial buildup is significantly different in these three craniosynostosis syndromes compared to the controls. CLINICAL RELEVANCE: The maxillary growth in patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is impaired, leading to a deviant dental development. Therefore, timely orthodontic follow-up is recommended. In order to increase expertise and support treatment planning by medical and dental specialists for these patients, and also because of the specific differences between the syndromes, we recommend the management of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis in specialized multidisciplinary teams.

Deviating dental arch morphology in mild coronal craniosynostosis syndromes.

OBJECTIVES: To determine whether the intramaxillary relationship of patients with Muenke syndrome and Saethre-Chotzen syndrome or TCF12-related craniosynostosis are systematically different than those of a control group. MATERIAL AND METHODS: Forty-eight patients (34 patients with Muenke syndrome, 8 patients with Saethre-Chotzen syndrome, and 6 patients with TCF12-related craniosynostosis) born between 1982 and 2010 (age range 4.84 to 16.83 years) that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands, were included. Forty-seven syndromic patients had undergone one craniofacial surgery according to the craniofacial team protocol. The dental arch measurements intercanine width (ICW), intermolar width (IMW), arch depth (AD), and arch length (AL) were calculated. The control group existed of 329 nonsyndromic children. RESULTS: All dental arch dimensions in Muenke (ICW, IMW, AL, p < 0.001, ADmax, p = 0.008; ADman, p = 0.002), Saethre-Chotzen syndrome, or TCF12-related craniosynostosis patients (ICWmax, p = 0.005; ICWman, IMWmax, AL, p < 0.001) were statistically significantly smaller than those of the control group. CONCLUSIONS: In this study, we showed that the dental arches of the maxilla and the mandible of patients with Muenke syndrome and Saethre-Chotzen syndrome or TCF12-related craniosynostosis are smaller compared to those of a control group. CLINICAL RELEVANCE: To gain better understanding of the sutural involvement in the midface and support treatment capabilities of medical and dental specialists in these patients, we suggest the concentration of patients with Muenke and Saethre-Chotzen syndromes or TCF12-related craniosynostosis in specialized teams for a multi-disciplinary approach and treatment.

A micro-pipette thermal sensing technique for measuring the thermal conductivity of non-volatile fluids.

This research work demonstrates an innovative technique to measure the thermal conductivity of a small volume of non-volatile liquids. The method utilizes a micro-pipette thermal sensor (MPTS) (tip diameter < 2 µm) and is based on laser point heating thermometry and transient heat transfer. A laser beam is irradiated at the sensor tip immersed in a few microliters of the test fluid and the transient temperature change is recorded with the sensor. This temperature change is dependent on the surrounding fluid's thermal properties, such as thermal conductivity and diffusivity. The numerical solution for transient temperature profile for a point source is obtained using the finite element method in the COMSOL software. To determine the optimizing parameters such as thermal conductivity and power absorbed at the sensor tip, the multi-parameter fitting technique is used in MATLAB, which will fit the COMSOL simulation result with the experimental data. Three liquids with known thermal conductivity were tested to verify that the technique can be used to determine the thermal conductivity with high accuracy, and in addition, the thermal conductivity of growth media and serum used for culturing cancer cells is estimated. With the sensor size of 1-2 µm, we demonstrate the possibility of using this described method as the MPTS technique for measuring the thermal properties of microfluidic samples and biological fluids.

Carotid ultrasound measurements for assessing fluid responsiveness in spontaneously breathing patients: corrected flow time and respirophasic variation in blood flow peak velocity.

BACKGROUND: This study evaluated the ability of two Doppler ultrasound-derived parameters, the carotid corrected flow time (FTc) and respirophasic variation in carotid artery blood flow peak velocity (ΔVpeak), to predict fluid responsiveness in spontaneously breathing patients. METHODS: A total of 53 spontaneously breathing patients were studied before anaesthetic induction for neurosurgery. Carotid FTc, ΔVpeak, and haemodynamic data were measured before and after administration of 6 ml kg-1 colloid. Fluid responsiveness was defined as a 15% or more increase in stroke volume index as assessed by transthoracic echocardiography after the fluid challenge. RESULTS: Twenty-two (42%) patients were fluid responders. The areas under the receiver operating characteristic curves for FTc and ΔVpeak were 0.842 [95% confidence interval (CI) 0.735-0.948, P<0.001] and 0.818 (95% CI: 0.701-0.935, P<0.001), respectively. The optimal cut-off values of FTc and ΔVpeak for fluid responsiveness were 349.4 ms (sensitivity of 72.7%; specificity of 83.9%) and 9.1% (sensitivity of 72.7%; specificity of 87.1%), respectively. The grey zone for FTc was 346.9-361.0 ms and included 28% of the patients, and the grey zone for ΔVpeak was 6.5-10.2% and included 50% of the patients. CONCLUSIONS: Using Doppler ultrasound-derived parameters measured at the carotid artery, FTc predicted fluid responsiveness in spontaneously breathing patients better than ΔVpeak. However, further studies are warranted before these parameters are recommended for clinical use. CLINICAL TRIAL REGISTRATION: NCT 02843477.

Optimising the effectiveness of diabetes education in an East Asian population.

AIM: To explore the collective patterns of learning behaviours and preferences of Chinese people during diabetes education. The study was carried out across three countries and aimed to identify strategies that could be used to tailor diabetes education to Chinese people. METHODS: A case study approach was undertaken in three countries (Australia, China and Singapore) using participant observations and qualitative interviews. Purposive sampling was used to select field sites before a snowball technique was employed to identify relevant interviewees. Thematic analysis with pattern matching was used for data analysis. RESULTS: A total of 39 participant observations and 22 interviews were conducted. Chinese people with diabetes were observed seeking advice and recommendations from health professionals. When told clearly what to do, they strived for full compliance. They tended to be submissive during diabetes education and were not likely to raise concerns, negotiate or participate in making medical decisions. They appeared to prefer prescriptive concrete instructions rather than more flexible conceptual education and to believe that behavioural change should be achieved by individual willpower and determination, resulting in an 'all-or-nothing' approach. Regular repeated information sessions were reported to establish rapport and trust. CONCLUSIONS: For diabetes education to be culturally modified for Chinese people, there is a need to consider their unique philosophies and behaviours during education to support lifestyle changes. Building trust from the early stages of education was achieved by encouraging rapport through the provision of clear and precise instructions. This should be done before engaging in an open discussion of implementation strategies. Once the trust is built, healthy behaviour change may follow.

Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERß) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol - ERß signaling in mediating DOL effects in male mice to further decipher sex differences. METHODS: Male 21 day-old WT and ERßKO male mice were treated with either placebo or estradiol and exposed to normal or DOL for 4 weeks. Cartilage thickness and cell proliferation, gene expression and immunohistochemistry of chondrogenic markers and estrogen receptor alpha (ERα), and analysis of bone histomorphometry via microCT were completed to ascertain the effect of estradiol on DOL effects to the TMJ. RESULTS: ERßKO male mice lack a MCC phenotype. In both genotypes, estradiol treatment increased Col2 gene expression and trabecular thickness. DOL in combination with estradiol treatment caused a significant increase in Col2 gene expression in both genotypes. CONCLUSIONS: The sex differences in DOL-induced inhibition of Col2 expression do not appear to be mediated by differences in estradiol levels between male and female mice. Greater understanding on the role of estrogen and altered loading are critical in order to decipher the sex dimorphism of TMJ disorders.

Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role for female hormones in the disease process. However, little is known about the role of estrogen receptor (ER) signaling in regulating mandibular condylar cartilage growth. Therefore, the goal of this study was to examine the effects of altered estrogen levels on the mandibular condylar cartilage in wild type (WT) and ER beta Knockout (KO) mice. MATERIALS AND METHODS: 21-day-old female WT (n = 37) and ER beta KO mice (n = 36) were either sham operated or ovariectomized, and treated with either placebo or estradiol. The mandibular condylar cartilage was evaluated by histomorphometry, proliferation was analyzed by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and assays on gene and protein expression of chondrocyte maturation markers were performed. RESULTS: In WT mice, ovariectomy caused a significant increase in mandibular condylar cartilage cell numbers, a significant increase in Sox9 expression and a significant increase in proliferation compared with sham operated WT mice. In contrast, ovariectomy did not cause any of these effects in the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo. Estrogen replacement treatment in ovariectomized ER beta KO mice caused a significant increase in Col2 expression, no change in ER alpha expression, and a significant increase in Sost expression. CONCLUSION: Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression.

A circuit analysis of an in situ tunable radio-frequency quantum point contact.

A detailed analysis of the tunability of a radio-frequency quantum point contact setup using a C - LCR circuit is presented. We calculate how the series capacitance influences resonance frequency and charge-detector resistance for which matching is achieved as well as the voltage and power delivered to the load. Furthermore, we compute the noise contributions in the system and compare our findings with measurements taken with an etched quantum point contact. While our considerations mostly focus on our specific choice of matching circuit, the discussion of the influence of source-to-load power transfer on the signal-to-noise ratio is valid generally.

Insular cortex is a trait marker for pain processing in fibromyalgia syndrome--blood oxygenation level-dependent functional magnetic resonance imaging study in Korea.

OBJECTIVES: To investigate the variability in cerebral activation according to pain intensity and the association between variability in cerebral activation and clinical features in patients with fibromyalgia syndrome (FMS) using functional magnetic resonance imaging (fMRI). METHODS: Nineteen FMS female patients and 22 age-matched healthy female controls were enrolled in this study. Changes in cerebral activation area were measured using blood oxygenation level-dependent (BOLD) contrast fMRI after application of both medium and high pressure stimuli to the left thumbnail bed. RESULTS: We identified the insular cortex (IC) and superior temporal gyrus (STG) as regions of interest (ROIs) in this analysis. Cerebral activation at the bilateral IC in response to high pressure stimuli was significantly greater in FMS patients than it was in the controls, whereas there were no differences in BOLD signal changes in the STG regions between FMS patients and controls, irrespective of pain level. Prominent signal changes at both ROIs in FMS patients were noted between high and medium pressure (p<0.001 contralateral IC, p=0.001 for ipsilateral IC, p=0.008 for contralateral STG, and p=0.049 for ipsilateral STG). BOLD signal changes on the contralateral STG after medium stimuli were correlated with tender point count (r=0.586, p=0.013). CONCLUSIONS: This study revealed more distinct signal variability in the ICs in FMS patients than in those of controls in response to high pressure stimuli. The IC can therefore be considered to be a region susceptible to pain perception in FMS patients.

Awareness and reported consequences of a cigarette tax increase among older adolescents and young adults.

PURPOSE: To determine the prevalence and predictors of the awareness of cigarette price increases following a cigarette tax increase, and assess the association of the tax increase and attempts to quit and reduce smoking among adolescents and young adults. DESIGN: We used a prospective cohort design. SETTING: Surveys were conducted in Minnesota before and after a $0.75 cigarette tax increase. SUBJECTS: We surveyed 3167 adolescents and young adults, including a subsample of 781 past-30-day smokers. MEASURES: Outcome measures were awareness of cigarette price increases and, among past-30-day smokers, reported changes in smoking behaviors because of the tax increase. Predictors included demographics, social factors, and prior smoking behaviors. ANALYSIS: We estimated the prevalence of the outcomes and their associations with the predictors using logistic regression. RESULTS: Among all participants, 42% noticed an increase in cigarette prices after the tax increase, including 76% of past-30-day smokers. Being a heavier smoker, living with smokers, having more smoking close friends, and generally being aware of cigarette price changes prospectively predicted the awareness of the price increase after the tax increase. Among past-30-day smokers, 16.7% reported quit attempts and 24.1% reported reducing smoking because of the tax increase. CONCLUSION: Because fewer than half of the participants noticed the cigarette tax increase, media campaigns to raise awareness of tax changes may increase their effectiveness.

Graphite patterning in a controlled gas environment.

Although a number of methods using scanning probe lithography to pattern graphene have already been introduced, the fabrication of real devices still faces limitations. We report graphite patterning using scanning probe lithography with control of the gas environment. Patterning processes using scanning probe lithography of graphite or graphene are normally performed in air because water molecules forming the meniscus between the tip and the sample mediate the etching reaction. This water meniscus, however, may prevent uniform patterning due to its strong surface tension or large contact angle on surfaces. To investigate this side effect of water, our experiment was performed in a chamber where the gas environment was controlled with methyl alcohol, oxygen or isopropanol gases. We found that methyl alcohol facilitates graphite etching, and a line width as narrow as 3 nm was achieved as methyl alcohol also contains an oxygen atom which gives rise to the required oxidation. Due to its low surface tension and highly adsorptive behavior, methyl alcohol has advantages for a narrow line width and high speed etching conditions.

Isolation of embryonic stem cells from enhanced green fluorescent protein-transgenic mouse and their survival in the cochlea after allotransplantation.

BACKGROUND: To study cell replacement therapy using embryonic stem (ES) cells in mice, avoiding immune rejection and tracing the fate of transplanted cells are important issues. This study was carried out to isolate ES cells ubiquitously expressing enhanced green fluorescent protein (EGFP) and test the survival of these cells in allografts in the cochlea of inbred C57BL/6 mice. METHODS: Putative ES cells were isolated from blastocysts collected from C57BL/6-green mice ubiquitously expressing EGFP. Pluripotency of these cells was tested by expression of stem cell markers and in vitro differentiation of the cells into embryoid bodies. Isolated EGFP-transgenic ES cells were injected into the cochlea of deafened inbred C57BL/6 mice, and survival of transplanted cells was identified in histologic sections of the cochlea. RESULTS: Putative ES cells expressed cellular markers for ES cells, including alkaline phosphatase, Oct-4, Nanog and stage-specific embryonic antigen-1. These cells formed embryoid bodies in suspension cultures. Incorporation of transplanted cells was found at the area of spiral ganglion neurons, auditory nerve fibers reaching the organ of Corti and stria vascularis in the scala media. Grafted cells were also found at the location of inner hair cells underneath the tectorial membrane. DISCUSSION: The isolation of ES cells from the EGFP-transgenic mouse and transplantation into allogeneic inbred mice may be a useful means of studying cell therapy with respect to the ubiquitous and stable expression of EGFP and elimination of graft rejection.

Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome.

BACKGROUND: Pseudolymphoma syndrome (PLS) is relatively rare but can lead to death if there are extensive skin lesions, severe hepatitis, agranulocytosis and neutropenia. PLS may also give rise to harmful effects if misdiagnosed as malignant lymphoma and patients with PLS are treated unnecessarily with chemotherapy, because it may mimic histologically other lymphomas, including mycosis fungoides (MF). OBJECTIVES: To examine the clinicopathological and genotypic features of anticonvulsant-induced PLS. Patients and methods We retrospectively reviewed clinical, laboratory and histological findings for eight cases of anticonvulsant-induced PLS, and performed T-cell receptor gene rearrangement using polymerase chain reaction with paraffin-embedded specimens from each case. RESULTS: The causative agents were carbamazepine (four cases), phenytoin (two cases), phenobarbital (one case) and valproic acid (one case). A cross-reaction between phenobarbital and phenytoin was observed in one case. The duration from the start of anticonvulsant therapy to skin eruption was 3-24 weeks (mean 7 weeks). The skin lesions were generalized maculopapular eruptions in all cases, including one case accompanied by vesiculopustular lesions. The frequencies of the associated features were as follows: facial oedema (88%), fever (75%), lymphadenopathy (63%), and hepatomegaly (25%). Laboratory findings revealed leukocytosis, atypical lymphocytes, eosinophilia, monocytosis, neutrophilia, lymphocytosis and abnormal liver function. Histopathologically, there was similarity between PLS and MF in that epidermotrophism of atypical lymphocytes (100%) and Pautrier's microabscess-like structures (38%) were observed. However, PLS has some differences from MF that include moderate to marked spongiosis (75%), necrotic keratinocytes (63%), and infiltration of eosinophils (25%) in the epidermis and, in the dermis, papillary dermal oedema (100%), extravasated erythrocytes (100%), lymphocytes within the dermis larger than those within the epidermis (63%), and infiltration of various inflammatory cells including neutrophils (50%). Genotypic analysis demonstrated a rearrangement of the T-cell receptor-gamma gene in one of eight cases studied. There were no deaths and all cases were improved at 2-9 weeks (mean 6 weeks), after the cessation of causative agents, systemic and topical corticosteroid therapy, and symptomatic therapy. There were no significant differences in clinical, laboratory and histological findings between the causative agents. CONCLUSIONS: PLS may show histopathological findings similar to MF and take a prolonged course even after the cessation of causative agents. Thus, a clear understanding and diagnosis of this disease is considered to have an important effect on treatment and prognosis.

Mycosis fungoides presenting as Ofuji's papuloerythroderma.

We report three patients presented with clinical features of Ofuji's papuloerythroderma (pruritic erythematous papules and extensive erythema sparing all skin folds), however, showing histopathological findings of mycosis fungoides (Pautrier's microabscess, haloed lymphocytes, disproportionate epidermotropism, and wiry collagen bundles). One case was associated with plaque stage of mycosis fungoides and follicular mucinosis. T-cell receptor (TCR) gene rearrangement analysis in the lesional skin tissue demonstrated rearrangement of the gamma chain in all cases. HTLV-1 serology was negative for two patients who conducted HTLV-1 test. We think that Ofuji's papuloerythroderma might be a variant of early mycosis fungoides rather than secondary skin manifestations to certain cutaneous inflammatory diseases.

A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).

Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.

Cloning and sequence analysis of the interleukin-8 gene from flounder (Paralichthys olivaceous).

A cDNA library of mRNA from flounder leukocytes stimulated with bacterial lipopolysaccharide (LPS) and hemagglutinin was constructed to clone cytokine genes of this fish. Initial screening of this library with human cytokine gene probes was not productive and clones with inserts of over 400 nucleotides (nt) were randomly sequenced, and a homologue of the vertebrate interleukin-8 (IL-8) gene was isolated. The flounder IL-8 cDNA encompassed 884 nt, including a coding region of 330 nt. Four cysteines characteristic of CXC chemokines were identified at conserved locations in the putative protein. The deduced amino acid sequence showed 36 and 35% sequence identity with counterpart genes in monkey and human, respectively, and 52% sequence similarity with these genes. However, the putative flounder IL-8 amino acid sequence showed 25% identity and 52% similarity to that of lamprey, the only other piscine IL-8 gene that has been cloned. Flounder IL-8 transcripts were detected in the head-kidney and spleen of LPS-injected flounder and leukocytes stimulated with LPS. It was not detected in the muscle or liver of LPS-injected flounder, tissues taken from non-stimulated flounder and non-stimulated leukocytes.