Resolution of severe neurobehavioral difficulties in an individual with Primrose syndrome with sertraline.

Primrose syndrome (PS) is a rare genetic disease characterized by developmental delay, intellectual disability, sensorineural hearing loss, and dysmorphic features. PS is caused by de novo pathogenic variants in the ZBTB20 gene, which encodes a transcription factor modulating neurogenesis. We describe resolution with sertraline of neurobehavioral difficulties in a 17-year-old Hispanic male with PS with de novo heterozygous c.1916G > A (p.C639Y) variant of ZBTB20. Neurobehavioral difficulties included aggression towards self and others, irritability, tearfulness, and mood liability that did not respond to behavioral interventions or aripiprazole. Treatment with sertraline, a medication indicated for psychiatric disorders including anxiety and depression, led to the resolution of neurobehavioral difficulties after 2 weeks of initiation of medication. The treatment course suggests that selective serotonin reuptake inhibitors, such as sertraline, may be a useful tool for neurobehavioral difficulties in PS over antipsychotics that are accompanied by complex side effect profiles, and suggest that anxiety is the primary cause of the neurobehavioral difficulties in this patient.

Marine litter pollution of breeding colony and habitat use patterns of Black-tailed gulls in South Korea.

Marine litter can affect the survival of the breeding population in seabird colonies. In this study, five 5 m × 5 m quadrats were installed at a Black-tailed gull (Larus crassirostris) breeding colony on Nan Island to collect marine litter and regurgitated pellets, from which the types, sizes, and quantities of marine litter were identified. Global positioning system (GPS) devices were attached to five adult gulls to investigate their major foraging habitats during the breeding period. Eighty-two pieces of marine litter were found, of which 74.4 % were related to fishing; all pellets contained fishing-related marine litter. Over half of the foraging habitats included fishing areas (ports and fish farms). This study is the first to quantitatively demonstrate the exposure of breeding colonies of Black-tailed gulls, the most dominant Korean seabird, to marine litter pollution during the breeding period; the birds forage predominantly in fishing areas close to their breeding colonies during this period.

Correlation Between Average Segment Width and Gamma Passing Rate as a Function of MLC Position Error in Volumetric Modulated Arc Therapy.

OBJECTIVE: This study analyzed the correlation between the average segment width (ASW) and gamma passing rate according to the multi-leaf collimator (MLC) position error. METHOD: To evaluate the changes in the gamma passing rate according to the MLC position error, 21 volumetric modulated arc therapy (VMAT) plans were generated using pelvic lymph node metastatic prostate cancer patient's data which is sensitive to MLC position errors as they involve several long, narrow, irregular fields. The ASW for each VMAT plan was calculated using our own code developed using Visual Basic for Applications (VBA). The gamma passing rate of the VMAT plan according to the MLC position error was evaluated using ArcCHECK (Sun Nuclear, Melbourne, FL, USA) while inducing symmetric MLC position errors in 0.25 mm intervals from -1 mm to +1 mm in the infinity medical linear accelerator (Elekta AB, Stockholm, Sweden). Finally, we examined the correlation between the change in the passing rate (γgradient) due to the MLC position error and the ASW in VMAT through linear regression analysis using the least squares method. RESULTS: The ASW and γgradient were found to have a linear correlation according to the MLC position error, and the coefficient of determination was 0.88. For a 1 mm position error of MLC in VMAT, the gamma passing rate improved by approximately 11.9% as the ASW increased by 10 mm. CONCLUSION: These results are expected to be employed as guidelines to minimize the dose uncertainty due to MLC position error in VMAT.

Evaluation of monoxide film-based dosimeters for surface dose detection in electron therapy.

Generally, electron therapy is applied to tumors on or close to the skin surface. However, this causes a variety of skin-related side effects. To alleviate the risk of these side effects, clinical treatment uses skin dosimeters to verify the therapeutic dose. However, dosimeters suffer from poor accuracy, because their attachment sites are approximated with the help of naked eyes. Therefore, a dosimeter based on a flexible material that can adjust to the contours of the human body is required. In this study, the reproducibility, linearity, dose-rate dependence, and percentage depth ionization (PDI) of PbO and HgO film-based dosimeters are evaluated to explore their potential as large-scale flexible dosimeters. The results demonstrate that both dosimeters deliver impressive reproducibility (within 1.5%) and linearity (≥ 0.9990). The relative standard deviations of the dose-rate dependence of the PbO and HgO dosimeters were 0.94% and 1.16% at 6 MeV, respectively, and 1.08% and 1.25% at 9 MeV, respectively, with the PbO dosimeter outperforming the 1.1% of existing diodes. The PDI analysis of the PbO and HgO dosimeters returned values of 0.014 cm (-0.074 cm) and 0.051 cm (-0.016 cm), respectively at 6 MeV (9 MeV) compared to the thimble chamber and R50. Therefore, the maximum error of each dosimeter is within the allowable range of 0.1 cm. In short, the analysis reveals that the PbO dosimeter delivers a superior performance relative to its HgO counterpart and has strong potential for use as a surface dosimeter. Thus, flexible monoxide materials have the necessary qualities to be used for dosimeters that meet the requisite quality assurance standards and can satisfy a variety of radiation-related applications as flexible functional materials.

Which Is Better for Liver SBRT: Dosimetric Comparison Between DCAT and VMAT for Liver Tumors.

Stereotactic body radiotherapy (SBRT) is currently well-adopted as a curative treatment for primary and metastatic liver tumors. Among SBRT methods, dynamic conformal arc therapy (DCAT) and volumetric-modulated arc therapy (VMAT) are the most preferred methods. In this study, we report a comparison study measuring the dose distribution and delivery efficiency differences between DCAT and VMAT for liver SBRT. All patients who were treated with SBRT for primary or metastatic liver tumors with a curative aim between January 2016 and December 2017 at DIRAMS were enrolled in the study. For all patients, SBRT plans were designed using the Monte Carlo (MC) algorithm in Monaco treatment planning system (version 5.1). The planning goals were set according to the RTOG 0813, RTOG 0915, and RTOG 1112 protocols. A plan comparison was made on the metrics of dose volume histogram, planning and delivery efficiency, monitor unit (MU), and dosimetric indices. PTV coverage was evaluated using the following: Dmean, D95%, D98%, D2%, D50%, Dmax, V95%, heterogeneity index (HI), and conformality index (CI). For DCAT and VMAT, respectively, the Dmean was 5942.8 ± 409.3 cGy and 5890.6 ± 438.8 cGy, D50% was 5968.8 ± 413.1 cGy and 5954.3 ± 405.2 cGy, and CI was 1.05 ± 0.05 and 1.03 ± 0.04. The D98% and V95% were 5580.0 ± 465.3 cGy and 20.4 ± 12.0 mL for DCAT, and 5596.0 ± 478.7 cGy and 20.5 ± 12.0 mL for VMAT, respectively. For normal liver, V40, V30, V20, V17, V5, Dmean, Dmax were evaluated for comparison. The V30, V20, and V10 were significantly higher in DCAT; other parameters of normal livers showed no statistically significant differences. For evaluation of intermediate dose spillage, D2cm(%) and R50% of DCAT and VMAT were 45.8 ± 7.9 and 5.6 ± 0.9 and 45.1 ± 6.7 and 5.5 ± 1.2, respectively. Planning and delivery efficiency were evaluated using MU, Calculation time, and Delivery time. DCAT had shorter Calculation time and Delivery time with smaller MU. MU was smaller in DCAT and the average difference was 300.1 MU. For liver SBRT, DCAT is an effective alternative to VMAT plans that could meet the planning goals proposed by the RTOG SBRT protocol and increases plan and delivery effectiveness, while also ignoring the interplay effect.

Clinical Experience of Vibroplasty With Direct Coupling to the Oval Window Without Use of a Coupler.

OBJECTIVES/HYPOTHESIS: To investigate the efficacy of direct implantation of a Vibrant Soundbridge (VSB) implant in the oval window (OW) without the use of an OW coupler in patients with severe mixed hearing loss. STUDY DESIGN: Retrospective chart review METHODS: A total of 62 patients underwent VSB implantation between July 2016 and December 2018 at Severance Hospital in Seoul, South Korea. Among them, eight patients (nine ears) with moderate-to-severe mixed hearing loss were implanted with a VSB directly in the OW. A floating mass transducer (FMT) was attached to the stapes footplate and covered with tragal cartilage. The outcomes were evaluated using pure-tone audiogram and speech audiogram preoperatively and postoperatively. Word recognition score (WRS; % correct) were measured at the most comfortable loudness (MCL) level to evaluate speech perception. RESULTS: All cases posed difficulty with round window vibroplasty during surgery, and eventually, an FMT was appropriately placed in the OW without a coupler. Preoperative and postoperative bone conduction thresholds were not different. VSB-aided threshold improved in terms of functional and effective gains. Interestingly, four cases showed improved air conduction thresholds without the use of a VSB. In addition, MCL level with a VSB was significantly lower than that with a hearing aid, and VSB-aided WRS improved over time. CONCLUSIONS: Direct implantation of a VSB in the OW without the use of a coupler showed favorable hearing outcomes, and the OW vibroplasty was safe. Direct OW vibroplasty without a coupler is a reliable procedure and can be a good option for hearing rehabilitation in patients with severe mixed hearing loss. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

Which Patients With a Unilateral Hearing Aid for Symmetric Sensorineural Hearing Loss Have Auditory Deprivation?

OBJECTIVES: The aim of study is to find conditions that aggravate auditory deprivation in patients with symmetric hearing loss after unilateral digital, non-linear hearing aid (HA). METHODS: In the retrospective case-comparison study, we assessed 47 patients with symmetric sensorineural hearing loss (SNHL), wearing unilateral conventional HAs. Audiological outcomes were assessed >1 year after HA fitting (mean duration, 31.0 months). Pure-tone audiometry in HA-aided and HA-unaided conditions was performed over time. Word recognition score (WRS) was evaluated at the most comfortable listening level. RESULTS: The initial pure tone average of four frequency thresholds at 500, 1,000, 2,000, and 4,000 Hz (PTA4) did not show a difference of >5 dB HL between HA-aided and HA-unaided ears. WRS progressively decreased for both HA-aided and HA-unaided ears although the extent of decrease was significantly greater for HA-unaided (7.6%) than for HA-aided ears (5.1%, P<0.05). Notably, auditory deprivation in HA-unaided ears was significantly greater in patients with an initial PTA4 ≥53 dB HL (P<0.001). CONCLUSION: Bilateral HAs are strongly recommended, particularly for patients with moderate to severe SNHL to prevent auditory deprivation in the contralateral ear.

Gasless transoral robotic thyroidectomy using the DaVinci SP system: Feasibility, safety, and operative technique.

BACKGROUND: Transoral robotic thyroidectomy (TORT) is an ideal method for minimally invasive thyroidectomy, as there is less flap dissection during the procedure and no postoperative scars. However, this method also has the limitation of present DaVinci system and some technical problems related to CO2 gas insufflation that must be resolved. We investigated the feasibility and safety of gasless TORT using the latest version of the DaVinci system (SP). METHODS: From October 2018 to January 2019, we performed 10 surgeries of gasless TORT using the DaVinci SP at Yonsei University Hospital. RESULTS: Nine patients underwent unilateral thyroid lobectomy and one patient received total thyroidectomy. All operations were successfully completed. Nine cases had papillary thyroid carcinoma, and one had benign nodules. The mean surgical time was 177 min, and the mean hospital stay was 6.3 days. There were no reports of transient or permanent vocal cord palsy, recurrence, or mortality during the follow-up period. Temporary hypoesthesia of the chin due to mental nerve injury was observed in 3 of 10 patients, but it recovered spontaneously within 1 months in all cases. CONCLUSIONS: Gasless TORT using the DaVinci SP system is feasible and safe for selected patients and is a potential alternative approach for scarless thyroid surgery.

Predictors of Institutionalization in Patients with Alzheimer's Disease in South Korea.

BACKGROUND AND PURPOSE: We investigated predictors of institutionalization in patients with Alzheimer's disease (AD) in South Korea. METHODS: In total, 2,470 patients with AD aged 74.5±7.8 years (mean±standard deviation, 68.1% females) were enrolled from November 2005 to December 2013. The dates of institutionalization were identified from the public Long-Term-Care Insurance program in January 2014. We used a Cox proportional-hazards model to identify predictors for future institutionalization among characteristics at the time of diagnosis in 2,470 AD patients. A similar Cox proportional-hazards model was also used to investigate predictors among variables that reflected longitudinal changes in clinical variables before institutionalization in 816 patients who underwent follow-up testing. RESULTS: A lower Mini Mental State Examination score [hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92-0.97] and higher scores for the Clinical Dementia Rating and Neuro-Psychiatric Inventory (HR=1.01, 95% CI=1.00-1.01) at baseline were independent predictors of institutionalization. The relationship of patients with their main caregivers, presence of the apolipoprotein E e4 allele, and medication at baseline were not significantly associated with the rate of institutionalization. In models with variables that exhibited longitudinal changes, larger annual change in Clinical Dementia Rating Sum of Boxes score (HR=1.15, 95% CI=1.06-1.23) and higher medication possession ratio of antipsychotics (HR=1.89, 95% CI=1.20-2.97) predicted earlier institutionalization. CONCLUSIONS: This study shows that among Korean patients with AD, lower cognitive ability, higher dementia severity, more-severe behavioral symptoms at baseline, more-rapid decline in dementia severity, and more-frequent use of antipsychotics are independent predictors of earlier institutionalization.

Apoptotic action of botulinum toxin on masseter muscle in rats: early and late changes in the expression of molecular markers.

The purpose of this study was to compare the early or late expression levels of p65, Bcl-2, and type II myosin and the frequency of TUNEL-positive nuclei in the rat masseter muscle after injection of different concentrations of botulinum toxin-A (BTX-A). We injected either 5 U or 10 U of BTX-A into both masseter muscles of the rat. As a control group, the same volume of saline was injected. After 2 or 12 weeks, the animals were sacrificed. Subsequently, a biopsy and immunohistochemical staining of the samples were performed using a p65, Bcl-2, or type II myosin antibody. Additionally, a TUNEL assay and transmission electron microscopic analysis were performed. The expression of p65, Bcl-2, and type II myosin increased significantly with increasing concentrations of BTX-A at 2 weeks after BTX-A injection (P < 0.05). The number of TUNEL-positive nuclei was also significantly increased in the BTX-A-treated groups in comparison to the saline-treated control at 2 weeks after BTX-A injection (P < 0.05). Elevated expression of Bcl-2 was also observed in 10-unit BTX-A-treated group at 12 weeks after injection (P < 0.05). At 12 weeks after injection, the number of enlarged mitochondria was increased, and many mitochondria displayed aberrations in cristae morphology after BTX-A injection. In conclusion, BTX-A injection into the masseter muscle increased the expression level of p65, Bcl-2, and type II myosin at an early stage. The morphological changes of mitochondria were more evident at 12 weeks after injection.

Early effect of Botox-A injection into the masseter muscle of rats: functional and histological evaluation.

BACKGROUND: The purpose of this study was to evaluate the change of food intake after different dosages of botulinum toxin A (BTX) injection in the animal model. Additionally, the dimensional and histological change at 14 days after BTX injection was also evaluated. METHODS: The comparative study was performed using the BTX injection model in rats (n = 5 for each group). Group 1 was the saline-injected group. Group 2 was the 5-unit BTX-injection group to each masseter muscle. Group 3 was the 10-unit BTX-injection group to each masseter muscle. Food intake rates and body weight were checked daily before and after BTX injection until 10 days. All animals were sacrificed at 14 days after BTX injection, and the specimens underwent hematoxylin and eosin stain and immunohistochemical staining for myosin type II (MYH2). RESULTS: The recovery of food intake in groups 2 and 3 decreased significantly compared with group 1 from day 2 to day 7 and day 9 after injection (p < 0.05). The BTX-treated masseter muscles were significantly smaller than those in group 1 (p = 0.015). The immunohistochemical findings demonstrated that the expression of MYH2 was significantly higher in group 3 compared to groups 1 and 2 (p < 0.001). CONCLUSIONS: BTX injection to the masseter muscle in rats demonstrated short food-intake-rate reduction with recovery until 10 days after injection. The thickness of the masseter muscle and MYH2 expression were significantly changed according to the injected dose of BTX.

Rhodopsin management during the light-dark cycle of Anopheles gambiae mosquitoes.

The tropical disease vector mosquito Anopheles gambiae possesses 11 rhodopsin genes. Three of these, GPROP1, GPROP3, and GPROP4, encode rhodopsins with >99% sequence identity. We created antisera against these rhodopsins and used immunohistology to show that one or more of these rhodopsins are expressed in the major R1-6 photoreceptor class of the adult A.gambiae eye. Under dark conditions, rhodopsin accumulates within the light-sensitive rhabdomere of the photoreceptor. Light treatment, however, causes extensive movement of rhodopsin to the cytoplasmic compartment. Protein electrophoresis showed that the rhodopsin is present in two different forms. The larger form is an immature species that is deglycosylated during the posttranslational maturation process to generate the smaller, mature form. The immature form is maintained at a constant level regardless of lighting conditions. These results indicate that rhodopsin biosynthesis and movement into the rhabdomere occurs at a constant rate. In contrast, the mature form increases in abundance when animals are placed in dark conditions. Light-triggered internalization and protein degradation counteracts this rhodopsin increase and keeps rhabdomeric rhodopsin levels low in light conditions. The interplay of the constant maturation rate with light-triggered degradation causes rhodopsin to accumulate within the rhabdomere only in dark conditions. Thus, Anopheles photoreceptors possess a mechanism for adjusting light sensitivity through light-dependent control of rhodopsin levels and cellular location.

Cephalometric predictors of long-term stability in the early treatment of Class III malocclusion.

The aim of this study was to examine the differences in the early craniofacial morphology of Class Ill malocclusions. Lateral cephalograms of 45 subjects with a Class III malocclusion and an anterior crossbite in the deciduous or mixed dentition were examined before treatment, after treatment, and during the long-term retention stage. The anterior crossbites of all patients were corrected after a series of orthodontic treatments. After a mean follow-up period of 5.7 years, all the subjects were reevaluated and divided into three groups according to the final occlusal status: good, fair, and poor occlusal stability. Twenty cephalometric variables on the pretreatment lateral cephalograms were analyzed by one-way analysis of variance and discriminant analysis to identify the key determinants for discriminating among the three groups. Among the 20 variables, 11 showed statistical significance. Generally, the subjects with a smaller gonial angle and a more hypodivergent skeletal pattern had good prognosis after the early treatment of Class III malocclusion. When the AB to mandibular plane angle and N-perpendicular to point A were selected in discriminant analysis, the AB to mandibular plane angle was the most significant variable. Discriminant analysis showed a relatively high degree of correct classifications of the patients with early Class III malocclusion. In particular, discriminant analysis showed the highest accuracy (93.3%) when predicting a poor prognosis.