Efficacy of Cranial Orthosis for Plagiocephaly Based on 2D and 3D Evaluation.

Background With the advent of cranial orthoses as therapeutic medical devices for the treatment of severe positional head deformities in Japan, an increasing number of patients are being treated with them. However, assessing the effectiveness of a treatment is often difficult due to the use of different metrics. This study aimed to evaluate the effectiveness of cranial orthoses for deformational plagiocephaly using two- (2D) and three-dimensional (3D) evaluation metrics. Methods We conducted a retrospective study of infant patients with deformational plagiocephaly who underwent cranial orthosis treatment. We evaluated the severity of deformational plagiocephaly using cranial asymmetry (CA) and the cranial vault asymmetry index (CVAI) as 2D metrics, and anterior and posterior symmetry ratios as 3D metrics. The patients were divided into 24 subgroups based on the initial severity of each outcome and their age at the start of treatment. We analyzed the changes in outcomes and correlations within improvements across the age and severity categories. Results Overall, 1,038 infants were included in this study. The mean CA, CVAI, and anterior and posterior symmetry ratios improved significantly after cranial orthosis treatment. The improvement in each score was greater in patients with more severe initial deformities and in those who underwent treatment at a younger age. Conclusion Cranial orthosis treatment was effective in correcting deformational plagiocephaly in infants, as demonstrated by improvements in both 2D and 3D metrics. Patients with more severe initial deformities and those who underwent treatment at a younger age showed greater improvement.

Effectiveness of continuous allergenic food intake for acute food protein-induced enterocolitis syndrome.

Continuous intake of allergenic food is a safe and efficient treatment strategy for patients with a prolonged course of acute food protein-induced enterocolitis syndrome. The initial dose, dose escalation rate, and starting age for continuous allergenic food intake need further clarification.

Effectiveness of allergen immunotherapy with house dust mite extract for pediatric bronchial asthma.

Aim: We compared the effectiveness of rush subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) using standardized house dust mite (HDM) extract for pediatric bronchial asthma (BA). Methods: We followed the pediatric BA treatment score during 3 years of treatment. We assessed the median time to no longer requiring long-term control pharmacotherapy (LTCP) for BA (LTCP-free). We compared the outcomes after adjustment for confounding factors and propensity score matching. Results: Patients in the HDM SCIT group achieved the LTCP-free status significantly earlier than those in the HDM SLIT group after adjustment for confounding factors and propensity score matching. Conclusion: Patients treated for pediatric BA with rush HDM SCIT had earlier onset of therapeutic effects than those with HDM SLIT.

Site-specific relaxation of peptide bond planarity induced by electrically attracted proton/deuteron observed by neutron crystallography.

In structural biology, peptide bonds, fundamental linkages between hundreds of amino acids, of which a protein molecule is composed, have been commonly treated as a plane structure just as Linus Pauling et al. proposed. In this paper, a site-specific peptide bond relaxation mechanism by deuterons whose localization has been suggested by neutron crystallography is proposed. Such deuteron was observed as an arm of neutron scattering length density protruding from the carbonyl oxygen atoms in the main chain in the omit map drawn by neutron crystallography of human lysozyme. Our comprehensive study using x-ray and neutron diffraction and 15 N chemical shifts of individual amide nitrogen atoms within the same peptide bond strongly suggests the relaxation of the electronic resonance structure because of site-specific modulation by protons/deuterons localized on the electron orbital of the carbonyl oxygen. All experimental data used in this examination were obtained at room temperature, which is preferable for enzymatic activity. Such a close interaction between the electron resonance structure of a peptide bond and the exchangeable protons/deuterons well agreed with that observed in an intermediate state in an amide hydrolytic reaction simulated by the ab-initio calculation including water molecules.

Comparison of static and dynamic symmetry between masseter-innervated and dual-innervated free multivector serratus anterior muscle transfer for complete facial paralysis.

PURPOSE: In this study, facial symmetry was compared between the masseter-innervated and dual-innervated free multivector serratus anterior muscle transfer (FMSAMT) methods. METHODS: Eighteen patients with unilateral complete facial paralysis underwent facial reanimation surgery between April 2006 and July 2019. The masseter-innervated FMSAMT group (Group M, n = 8) underwent end-to-end coaptation with the ipsilateral masseter nerve in one stage. The dual-innervated FMSAMT group (Group D, n = 10) underwent end-to-end coaptation with the masseter nerve and end-to-side coaptation with the contralateral facial nerve via cross-face nerve graft. They were further divided into the one-stage (Group D1, n = 5) and two-stage (Group D2, n = 5) subgroups. The durations of periods until the first visible muscle contraction with clenching, first spontaneous smile, and the completion of resting tone were evaluated. The possibility of a spontaneous smile and symmetry of the midline and horizontal deviation at rest and during voluntary smiling were compared between each group. RESULTS: Groups M and D differed significantly in the possibility of a spontaneous smile and improvement rate of midline deviation and horizontal deviation at rest (p < 0.001, p < 0.001, and p = 0.001, respectively) but not in the improvement rate of midline and horizontal deviation during voluntary smiling. The duration of the period until the completion of resting tone was significantly shorter in Group D1 than in Group D2 (p = 0.048); however, the possibility of a spontaneous smile and the improvement rate of midline and horizontal deviation were not significantly different. CONCLUSIONS: Dual-innervated FMSAMT was effective in guaranteeing a symmetrical resting tone, voluntary smiling, and reproducing a spontaneous smile.

Reconstruction of Extensive Diaphragmatic Defects Using the Rectus Abdominis Muscle and Fascial Flap.

Diaphragmatic reconstruction is required for extensive diaphragmatic defects associated with tumor resection. Methods using artificial mesh and autologous tissues, such as pedicled flaps, have been reported predominantly for diaphragmatic reconstruction. We present the case of a 61-year-old woman who presented with a 14 × 13 × 12 cm tumor in the abdominal cavity of the upper left abdomen on computed tomography. The diaphragm defect measuring 12 × 7 cm that occurred during excision of the malignant tumor was reconstructed using the rectus abdominis muscle and fascial flap. The flap has vertical and horizontal vascular axes; therefore, blood flow is stable. It also has the advantage of increasing the range of motion and reducing twisting of the vascular pedicles. Fascial flap does not require processing such as thinning and can be used during suture fixation. This procedure, which has rarely been reported so far, has many advantages and may be a useful option for diaphragm reconstruction.

Comparison of rush-subcutaneous and sublingual immunotherapy with house dust mite extract for pediatric allergic rhinitis: A prospective cohort study.

BACKGROUND: We aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for allergic rhinitis. METHODS: Participants with allergic rhinitis selected their treatment between HDM SCIT or HDM SLIT, according to their wishes. We prospectively followed symptoms of allergic rhinitis using the allergic rhinitis symptom medication score (ARSMS), along with adverse reactions, during the dose escalation and maintenance phases for two years. We compared the outcomes between propensity score-matched groups to adjust the confounding factors. RESULTS: After propensity score matching, 88 patients in the HDM SCIT (n = 44) and HDM SLIT groups (n = 44) remained for analysis. The HDM SCIT group showed significantly earlier effectiveness than the HDM SLIT group (median time to decrease in ARSMS [≥2 points]: 5.5 vs. 18.0 months, p < 0.001). The incidence of systemic reactions was not significantly different between the two groups in the dose escalation phase (68.2% vs. 56.8%, p = 0.379). In the maintenance phase, the incidence of systemic reactions was higher in the HDM SCIT group than in the HDM SLIT group (18.2% vs. 0%, p < 0.006). All 44 patients in the HDM SCIT group completed two years of treatment, while nine patients in the HDM SLIT group discontinued treatment. CONCLUSIONS: The HDM SCIT group showed an earlier onset of therapeutic effect and a lower discontinuation rate than the HDM SLIT group, although more severe systemic reactions were observed during the maintenance phase.

Age- and sex-based changes in spike protein antibody status after SARS-CoV-2 vaccination and effect of past-infection in healthcare workers in Osaka.

OBJECTIVE: We aimed to compare the changes in SARS-CoV-2 spike protein antibody titres based on age group and sex using paired blood sampling after vaccination in association with the presence of nucleocapsid protein antibody. METHODS: All participants were healthcare workers at Yao Municipal Hospital in Osaka who voluntarily provided peripheral blood samples (n = 636, men/women 151/485, mean age 45 years). We investigated the serial changes in SARS-CoV-2 spike protein antibody titres at 1 and 7 months after the second vaccination regarding their relationship with sex and age group. At 7 months, we also examined anti-nucleocapsid assays. Antibody titres were shown as logarithmic values and the differences were assessed using a paired or unpaired student's t-test as appropriate. RESULTS: Among participants younger than 30 years, the antibody titres of spike protein were significantly higher in women one (p = 0.005) and seven (p = 0.038) months after vaccination. However, among those aged 30-49 years, the antibody titres were not different between the sexes at either follow-up time point. In contrast, among those aged 50-59 years, between-sex differences in antibody titres were observed only at 7 months, which was associated with a significant reduction in men. A significant negative correlation was observed between the antibody titres for spike protein at both time points in participants with positive nucleocapsid protein antibody at 7 months (r = - 0.467, p = 0.043), although a significant positive correlation was observed in those with negative results (r = 0.645, p < 0.001), CONCLUSIONS: Between-sex differences in SARS-CoV-2 spike protein antibody titres by paired blood sampling at different time points after vaccination depended on age group. The presence of nucleocapsid protein antibody was associated with changes in spike protein antibody titres after vaccination.

Protonation states of hen egg-white lysozyme observed using D/H contrast neutron crystallography.

Hen egg-white lysozyme (HEWL) is an enzymatic protein with two acidic amino acids, Glu35 and Asp52, in its active site. Glu35 acts as a proton donor to the substrate and Asp52 interacts with the positively charged substrate, suggesting different protonation states of these residues. However, neutron crystallographic studies thus far have not provided a consistent picture of the protonation states of these residues. Only one study succeeded in observing the active protonation states of Glu35 and Asp52 in the triclinic crystal system. However, their active states in the most widely studied tetragonal crystal system are still unknown. The application of the D/H contrast technique in neutron crystallography improves the ability to locate exchangeable D/H atoms in proteins. In the present study, D2O and H2O solvent crystals were prepared. Each neutron data set was collected for only five days by combining a time-of-flight diffractometer (iBIX) and the spallation neutron source at the Japan Proton Accelerator Research Complex. The D/H contrast map provided better visualization of the D/H atoms in HEWL than the conventional neutron scattering length density map. The neutron D/H contrast map demonstrated the alternative protonation of the OE1 and OE2 atoms in the carboxyl group of Glu35. This alternative protonation occurs in the absence of a substrate, where high selectivity of the protonation site does not occur. In this case, only the OE1-HE1 bond attacks the substrate in an equilibrium between OE1-HE1 and OE2-HE2, or the H+ ion of the OE2-HE2 bond moves to the OE1 atom just before or after substrate binding to initiate the catalytic reaction. In contrast, the carboxyl group of Asp52 is not protonated. Protonation of the carboxyl group was not observed for other Asp and Glu residues. These results are consistent with results from NMR spectroscopy and explain the protonation states at the active site in the apo form of HEWL.

Evaluation of subcutaneous immunotherapy with birch pollen extract for pollen-food allergy syndrome.

Some patients with pollen-food allergy syndrome (PFAS) develop systemic symptoms along with oral allergy syndrome upon ingesting processed foods as well as raw fruits and vegetables. This study aimed to investigate the efficacy of subcutaneous immunotherapy with birch pollen extract for patients with PFAS associated with soybean allergy. Subcutaneous immunotherapy with birch pollen extract was introduced in 6 patients with PFAS caused by alder/birch pollen and soybean allergy. An oral food challenge for ingestible amount of soy milk was performed before and 1 year after initiating subcutaneous immunotherapy with birch pollen extract. Before the treatment, the median intake of soy milk was 1.5 mL (interquartile range [IQR], 1-2 mL). One year after the treatment initiation, the median intake of soy milk increased significantly to 150 mL (IQR, 20-200 mL). Systemic reactions occurred in 4 of 6 patients in the rapid escalation phase of the treatment. The results thus suggest that subcutaneous immunotherapy with birch pollen extract could be beneficial for patients with PFAS associated with soybean allergy despite concerns regarding systemic reactions.

Dual-innervated multivector muscle transfer using two superficial subslips of the serratus anterior muscle for long-standing facial paralysis.

Recent reports have described several cases of double muscle transfers to restore natural, symmetrical smiles in patients with long-standing facial paralysis. However, these complex procedures sometimes result in cheek bulkiness owing to the double muscle transfer. We present the case of a 67-year-old woman with long-standing facial paralysis, who underwent two-stage facial reanimation using two superficial subslips of the serratus anterior muscle innervated by the masseteric and contralateral facial nerves via a sural nerve graft. Each muscle subslip was transferred to the upper lip and oral commissures, which were oriented in different directions. Furthermore, a horizontal fascia lata graft was added at the lower lip to prevent deformities such as lower lip elongation and deviation. Voluntary contraction was noted at roughly 4 months, and a spontaneous smile without biting was noted 8 months postoperatively. At 18 months after surgery, the patient demonstrated a spontaneous symmetrical smile with adequate excursion of the lower lip, upper lip, and oral commissure, without cheek bulkiness. Dual-innervated muscle transfer using two multivector superficial subslips of the serratus anterior muscle may be a good option for long-standing facial paralysis, as it can achieve a symmetrical smile that can be performed voluntarily and spontaneously.

Early wound healing of the hard-palate mucosal harvest site using artificial dermis fixation by a transparent plate.

BACKGROUND: There are currently no guidelines for the postoperative wound management of the hard-palate donor site in cases involving mucosal harvesting. This study describes our experiences with the use of an artificial dermis for early epithelialization and transparent plate fixation in cases involving hard-palate mucosal harvesting. METHODS: A transparent palatal plate was custom-fabricated using a thermoplastic resin board. After mucosal harvesting, an alginic acid-containing wound dressing (Sorbsan) was applied to the donor site, which was then covered with the plate. After confirming hemostasis, the dressing was changed to artificial dermis a few days later, and the plate was fixed to the artificial dermis. The size of the mucosal defect ranged from 8×25 to 20×40 mm. RESULTS: Plate fixation was adequate, with no postoperative slippage or infection of the artificial dermis. There was no pain at the harvest site, but a slight sense of incongruity during eating was reported. Although the fabrication and application of the palatal plate required extra steps before and after harvesting, the combination of the artificial dermis and palatal plate was found to be very useful for protecting the mucosal harvest site, and resulted in decreased pain and earlier epithelialization. CONCLUSIONS: The combination of artificial dermis and a transparent palatal plate for wound management at the hard-palate mucosal donor site resolved some of the limitations of conventional methods.

Recent structural insights into the mechanism of lysozyme hydrolysis.

Lysozyme hydrolyzes the glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycans located in the bacterial cell wall. The mechanism of the hydrolysis reaction of lysozyme was first studied more than 50 years ago; however, it has not yet been fully elucidated and various mechanisms are still being investigated. One reaction system that has commonly been proposed is that the lysozyme intermediate undergoes covalent ligand binding during hydrolysis. However, these findings resulted from experiments performed under laboratory conditions using fluorine-based ligands, which facilitate the formation of covalent bonds between the ligands and the catalytic side chain of lysozyme. More recently, high-resolution X-ray structural analysis was used to study the complex of lysozyme with an N-acetylglucosamine tetramer. As a result, the carboxyl group of Asp52 was found to form a relatively strong hydrogen-bond network and had difficulty binding covalently to C1 of the carbohydrate ring. To confirm this hydrogen-bond network, neutron test measurements were successfully performed to a resolution of better than 1.9 Å.

Effect of postoperative radiotherapy for free flap volume changing after tongue reconstruction.

OBJECTIVE: The purpose of this study was to evaluate the effect of postoperative radiotherapy (RT) on temporal volume changes with a cutaneous free flap (CF) and a myocutaneous free flap (MCF). METHODS: The subjects were 24 men and 11 women (mean age, 50.5 ± 15.5 years) with tongue or floor of mouth cancer. Twenty-seven cases of CF and eight cases of MCF were selected. The flap volume change of the reconstructed tongue was calculated using computed tomography (CT) images taken immediately and at one year postoperatively using the DICOM image processing software OsiriX®. RESULTS: The reduction rate in flap volume at one year postoperatively was 82.0 ± 15% in CF without RT, 70.3 ± 26.1% in CF with RT, 88.5 ± 14.7% in MCF without RT, and 99.5 ± 16% in MCF with RT. The MCF volume was significantly higher compared to the CF volume. Although postoperative RT reduced the CF volume by 30%, there was only a slight reduction in the MCF volume. CONCLUSIONS: We evaluated the effect of postoperative RT on volume reduction in 35 cases of the reconstructed tongue with CF and MCF using a computer-assisted volume rendering technique. In this study, the effect of RT on volume reduction was different between the CF and MCF.

Neutron diffraction experiment with the Y116S variant of transthyretin using iBIX at J-PARC: application of a new integration method.

Transthyretin (TTR) is one of more than 30 amyloidogenic proteins, and the amyloid fibrils found in patients afflicted with ATTR amyloidosis are composed of this protein. Wild-type TTR amyloids accumulate in the heart in senile systemic amyloidosis (SSA). ATTR amyloidosis occurs at a much younger age than SSA, and the affected individuals carry a TTR mutant. The naturally occurring amyloidogenic Y116S TTR variant forms more amyloid fibrils than wild-type TTR. Thus, the Y116S mutation reduces the stability of the TTR structure. A neutron diffraction experiment on Y116S TTR was performed to elucidate the mechanism of the changes in structural stability between Y116S variant and wild-type TTR through structural comparison. Large crystals of the Y116S variant were grown under optimal crystallization conditions, and a single 2.4 mm3 crystal was ultimately obtained. This crystal was subjected to time-of-flight (TOF) neutron diffraction using the IBARAKI biological crystal diffractometer (iBIX) at the Japan Proton Accelerator Research Complex, Tokai, Japan (J-PARC). A full data set for neutron structure analysis was obtained in 14 days at an operational accelerator power of 500 kW. A new integration method was developed and showed improved data statistics; the new method was applied to the reduction of the TOF diffraction data from the Y116S variant. Data reduction was completed and the integrated intensities of the Bragg reflections were obtained at 1.9 Šresolution for structure refinement. Moreover, X-ray diffraction data at 1.4 Šresolution were obtained for joint neutron-X-ray refinement.

Current status and near future plan of neutron protein crystallography at J-PARC.

The IBARAKI Biological Crystal Diffractometer (iBIX) has been available for use at MLF (Material and Life Science Facility) in J-PARC (Japan Proton Accelerator Research Complex) since 2008. The development in state-of-the-art detector systems could enable iBIX to become one of the highest-performance neutron single-crystal diffractometers in the world. Here, together with other various developments, such as data reduction software, crystal growth, and new techniques in measurement coupled analysis, we provided new hydrogen and water structural data of several proteins and macromolecules. Although the proton power at MLF has not yet reached its planned maximum (1MW), a more powerful neutron source will be soon needed for neutron protein crystallography. A future idea is also proposed and discussed in this article.

Involvement of the ADAMTS13-VWF axis in acute Kawasaki disease and effects of intravenous immunoglobulin.

INTRODUCTION: ADAMTS13 modulates shear-dependent platelet thrombus formation (PTF) by limited proteolysis of von Willebrand factor (VWF). A high-plasma-ratio of VWF antigen to ADAMTS13 activity (VWF:Ag/ADAMTS13:AC) promotes PTF and aggravates shear-induced inflammation mediated by VWF. A role of ADAMTS13 in Kawasaki disease (KD) remains unknown, however. We investigated the involvement of ADAMTS13-VWF axis in the acute-phase of KD (acute-KD). METHODS: VWF:Ag and ADAMTS13:AC in 77 KD infants were measured at three time-points; immediately before (Pre), one-week (1 W) and one-month (1 M) after intravenous-immunoglobulin (IVIG) treatment. VWF multimer (VWFM) distribution and ADAMTS13-isoelectrofocusing (IEF) patterns were compared between the responders and non-responders to IVIG. RESULTS: A high VWF:Ag (195.7 ±â€¯85.6%, p < 0.05), low ADAMTS13:AC (60.3 ±â€¯23.8%, p < 0.05) and high VWF:Ag/ADAMTS13:AC ratio (3.70 ±â€¯2.12, p < 0.05) at Pre were seen compared to control plasmas. These parameters returned to normal levels time-dependently after IVIG treatment. Non-responders to IVIG demonstrated high VWF:Ag and low ADAMTS13:AC at Pre, and high VWF:Ag/ADAMTS13:AC ratio at 1 W compared to responders, but there were no significant differences in VWFM distribution between both groups. IEF analyses revealed the decreased free form of ADAMTS13 and increased complex form with ADAMTS13 and high-molecular-weight-VWFM at Pre in non-responders. A high VWF:Ag/ADAMTS13:AC ratio was associated with increased white blood cell counts, together with decreased serum albumin and sodium at Pre and 1 W. CONCLUSIONS: A high VWF:Ag/ADAMTS13:AC ratio in acute-KD persisted after primary treatment in non-responders, and unbalanced substrate-to-enzyme ratio appeared to associate with vascular endothelial damage. Analysis of existing mode of ADAMTS13 may help to clarify pathogenesis of IVIG resistance in acute-KD.

Multivector functioning muscle transfer using superficial subslips of the serratus anterior muscle for longstanding facial paralysis.

Various donor muscles have been identified for restoring facial function due to longstanding facial paralysis. Donor muscles such as the gracilis and latissimus dorsi are frequently used and often produce one or two reliable vectors of force. However, there are drawbacks of using these muscles, including the instability of separating multivector functioning muscle units and limited amount of muscle contraction. Serratus anterior muscle transfer has the advantages of multiple independently functioning motor units that can be created with a single neurovascular pedicle. This article describes multivector muscle transfer using two or three superficial subslips of the serratus anterior muscle on a single neurovascular pedicle to produce an esthetic smile that is customized to imitate the function of the contralateral mimetic muscles. Twelve patients who had longstanding unilateral facial paralysis underwent muscle transfer consisting of multivector superficial subslips of the serratus anterior muscle innervated by the ipsilateral masseteric nerve. The procedure had an uneventful postoperative course, and patients obtained excellent results, with sufficient upper lip excursion, mouth angle, and lower lip working simultaneously. Functioning muscle transfer using multivector superficial subslips of the serratus anterior muscle is effective for treating longstanding facial paralysis. This technique avoids postoperative bulkiness of the cheek muscle and achieves a more natural and symmetrical smile.