Efficacy of Random-start Controlled Ovarian Stimulation in Cancer Patients

This study aimed to evaluate the efficacy of random-start controlled ovarian stimulation (COS) in cancer patients for emergency fertility preservation. In this retrospective comparative study, 22 patients diagnosed with cancer and 44 infertile women undergoing conventional in vitro fertilization (IVF) were included. In cancer patients, ovarian stimulation was started on the day of referral, irrespective of their menstrual cycle date. The control group was selected by age matching among women undergoing conventional IVF. COS outcomes were compared between groups. The number of total and mature oocytes retrieved and the oocyte maturity rate were higher in the random-start group than in the conventional-start group. However, duration of ovarian stimulation was longer in the random-start group (11.4 vs. 10.3 days, P = 0.004). The addition of letrozole to lower the estradiol level during COS did not adversely affect total oocytes retrieved. However, oocyte maturity rate was lower in cycles with letrozole than in cycles without letrozole (71.6% vs. 58.2%, P = 0.019). Our study confirms the feasibility and effectiveness of random-start COS in cancer patients.

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Expanding the mutational spectrum of LZTR1 in schwannomatosis

Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.     

Identification of a novel nonsense mutation in the rod domain of GFAP that is associated with Alexander disease

Alexander disease (AxD) is an astrogliopathy that primarily affects the white matter of the central nervous system (CNS). AxD is caused by mutations in a gene encoding GFAP (glial fibrillary acidic protein). The GFAP mutations in AxD have been reported to act in a gain-of-function manner partly because the identified mutations generate practically full-length GFAP. We found a novel nonsense mutation (c.1000 G>T, p.(Glu312Ter); also termed p.(E312*)) within a rod domain of GFAP in a 67-year-old Korean man with a history of memory impairment and leukoencephalopathy. This mutation, GFAP p.(E312*), removes part of the 2B rod domain and the whole tail domain from the GFAP. We characterized GFAP p.(E312*) using western blotting, in vitro assembly and sedimentation assay, and transient transfection of human adrenal cortex carcinoma SW13 (Vim⁺) cells with plasmids encoding GFAP p.(E312*). The GFAP p.(E312*) protein, either alone or in combination with wild-type GFAP, elicited self-aggregation. In addition, the assembled GFAP p.(E312*) aggregated into paracrystal-like structures, and GFAP p.(E312*) elicited more GFAP aggregation than wild-type GFAP in the human adrenal cortex carcinoma SW13 (Vim⁺) cells. Our findings are the first report, to the best of our knowledge, on this novel nonsense mutation of GFAP that is associated with AxD and paracrystal formation.     

Unidentified Bright Objects on Brain Magnetic Resonance Imaging Affect Vestibular Neuritis

Objectives

The aim of this study was to investigate the differences in clinical manifestations of in two groups of vestibular neuritis (VN) patients with or without unidentified bright objects (UBOs).

Methods

A prospective, observational study with 46 patients diagnosed with VN between May 2013 and November 2013 was executed. A caloric test, a cervical vestibular-evoked myogenic potentials (cVEMPs) test, brain magnetic resonance imaging (MRI), spontaneous nystagmus test, head impulse test, and head-shaking nystagmus test were performed.

Results

Of the patients, 56.5% (n=26) were classified as UBO-positive by MRI. These showed lower caloric weakness and more prominent cVEMP asymmetry compared with the UBO-negative group (P<0.05). Total VN (TVN) was the most common in the UBO-positive group (45.0%), followed by superior VN (SVN, 30.0%), and inferior VN (IVN, 25.0%). However, in the UBO-negative group, SVN (75.0%) was the most common, followed by TVN and IVN (P<0.05). The recovery rate was not influenced by UBOs (P>0.05).

Conclusion

UBOs on T2-weighted or fluid attenuated inversion recovery MRI may affect the patterns of the vestibular nerve in patients with VN.     

Mutations at the APC exon 15 in the colorectal neoplastic tissues of serial array

Although the APC protein is known to participate in cellular proliferation and apoptosis, APC mutations have been thought to play a major role in the early stage of colorectal tumorigenesis. The somatic APC mutation of exon 15 was assessed to determine its impact on various stages of colorectal tumorigenesis. The colorectal neoplastic tissues of serial array studied included sporadic adenomas (group 1, n = 36), adenomas (group 2, n = 33), and carcinomas (group 3, n = 32) in the synchronous adenoma and carcinoma as well as sporadic carcinomas (group 4, n = 36). Aberrant DNA was detected by protein truncation test and confirmed by direct sequencing. The mutation prevalence was 36.1% in group 1, 45.5% in group 2, 59.4% in group 3, and 41.7% in group 4 with no differences among the groups. Among the 18 patients with synchronous adenoma and carcinoma, 9 had mutation in their adenomas and 12 in their carcinomas. The mutation loci and patterns did not differ in adenomas and carcinomas. Mutations in the mutation cluster region (MCR) were much more frequent than in the preceding region of MCR, i.e., 85.7% vs. 14.3%. The mutation prevalence of villous adenomas appeared greater than that of tubular adenoma (3/21 vs. 3/4). Predominant pathogenic mutations at MCR suggest that the APC mutation is implicated in all stages of colorectal tumorigenesis.     

Development of a parent-proxy quality-of-life chronic cough-specific questionnaire: clinical impact vs psychometric evaluations

BACKGROUND: Chronic cough affects at least 7% of children, and the impact of this on families is significant. Although adult cough-specific quality-of-life (QOL) instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QOL for parents of children with chronic cough exists. This article compares two methods of item reduction (clinical impact and psychometric) and reports on the statistical properties of both QOL instruments. METHOD: One hundred seventy children (97 boys and 73 girls; median age, 4 years; interquartile range, 3 to 7.25 years) and one of their parents participated. A preliminary 50-item parent cough-specific QOL (PC-QOL) questionnaire was developed from conversations with parents of children with chronic cough (ie, cough for > 3 weeks). Parents also completed generic QOL questionnaires (eg, Pediatric Quality of Life Inventory, version 4.0 [PedsQL4.0] and the 12-item Short Form Health Survey, version 2 [SF-12v2]). RESULTS: The clinical impact and psychometric method of item reduction resulted in 27-item and 26-item PC-QOL questionnaires, respectively, with approximately 50% of items overlapping. Internal consistency among the final items from both methods was excellent. Some evidence for concurrent and criterion validity of both methods was established as significant correlations were found between subscales of the PC-QOL questionnaire and the scales of the SF-12v2 and PedsQL4.0 scores. The PC-QOL questionnaire derived from both methods was sensitive to change following an intervention. CONCLUSION: Chronic cough significantly impacts on the QOL of both parents and children. Although the PC-QOL questionnaires derived from a clinical impact method and from a psychometric method contained different items, both versions were shown to be internally consistent and valid. Further testing is required to compare both final versions to objective and subjective cough measures.     

Remediation of trichloroethene (TCE)-contaminated groundwater by persulfate oxidation: a field-scale study

This study uses a trichloroethene (TCE)-contaminated site to determine the efficacy of persulfate oxidation for the treatment of TCE-contaminated groundwater. The main objectives of this study are: (1) to evaluate the efficacy of TCE treatment using persulfate with different injection strategies; (2) to determine the persistence of persulfate in the aquifer; (3) to determine the radius of influence (ROI) and transport distance of persulfate and (4) to determine the impact of persulfate on indigenous microorganisms during remediation. TCE concentrations are 0.26 mg L⁻¹ in P143 and 0.361 mg L⁻¹ in P146 and the microbial numbers are 6.1 × 10³ CFU mL⁻¹ in P143 and 4.4 × 10⁴ CFU mL⁻¹ in P146, before persulfate is injected. The results of the pilot study show that persulfate eliminates TCE. 100% of TCE is removed in P146 and 95% in P143. Single injection of a total amount of 275 kg of 5% persulfate produces better TCE removal than two half persulfate injections in sequence. The transport distance of persulfate ranges from 3.6 to 4.5 m. Persulfate also persists for 14 days in the aquifer. After persulfate is injected, the total bacterial counts decrease slightly to 2.4 × 10³ CFU mL⁻¹ in P143 and 1.8 × 10³ CFU mL⁻¹ in P146. When persulfate is consumed, the total bacterial counts increase but there is no recovery of the microbial community. The results show that sequential injections of a large amount of persulfate are suggested to maintain good long-term performance for TCE treatment.

This study uses a trichloroethene (TCE)-contaminated site to determine the efficacy of persulfate oxidation for the treatment of TCE-contaminated groundwater.     

Homogeneity and tolerance to heat of monolayer MoS2 on SiO2 and h-BN

We investigated the homogeneity and tolerance to heat of monolayer MoS₂ using photoluminescence (PL) spectroscopy. For MoS₂ on SiO₂, the PL spectra of the basal plane differ from those of the edge, but MoS₂ on hexagonal boron nitride (h-BN) was electron-depleted with a homogeneous PL spectra over the entire area. Annealing at 450 °C rendered MoS₂ on SiO₂ homogeneously electron-depleted over the entire area by creating numerous defects; moreover, annealing at 550 °C and subsequent laser irradiation on the MoS₂ monolayer caused a loss of its inherent crystal structure. On the other hand, monolayer MoS₂ on h-BN was preserved up to 550 °C with its PL spectra not much changed compared with MoS₂ on SiO₂. We performed an experiment to qualitatively compare the binding energies between various layers, and discuss the tolerance of monolayer MoS₂ to heat on the basis of interlayer/interfacial binding energy.

We investigated the homogeneity and tolerance to heat of monolayer MoS₂ using photoluminescence (PL) spectroscopy.     

Nonoperative Management of a Severe Proximal Rectus Femoris Musculotendinous Injury in a Recreational Athlete: A Case Report

This report describes a severe injury to the proximal rectus femoris (RF) muscle in a 37-year-old recreational athlete. This injury is a relatively rare occurrence in both the general and elite athletic populations. Acute and long-term imaging and functional outcomes are described. This athlete was able to return to full activity without surgical intervention. Follow-up imaging demonstrated gross healing of both complete (or near complete) muscle and tendon tears.