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Narrative review.To evaluate the availability and quality of breastfeeding guidelines for women with spinal cord injury (SCI).International Collaboration on Repair Discoveries (ICORD), Department of Medicine, Vancouver, BC.An environmental scan restricted to English language literature was performed to identify existing postpartum and breastfeeding guidelines. Guidelines were evaluated using a structured, validated tool (AGREE II) by 13 appraisers [medical/research experts (n = 10) and those with lived experience (n = 3)] from Vancouver and two international sites. Seven guidelines were evaluated across Domain 1 of the AGREE II tool to determine if they were applicable to mothers with SCI/physical disabilities. Domains 2 to 7 were evaluated if the guideline made mention of the SCI population.Of the seven guidelines evaluated, only one mentioned SCI (Postpartum Care in SCI from BC Women's Hospital). Other guidelines were excluded from further evaluation as they did not address the issue of breastfeeding in women with SCI. The overall scaled score for this guideline was 34.5%. There was significant variability between domains but no AGREE II domain scored greater than 50%, indicating substantial limitations.Current breastfeeding guidelines are not targeted to persons with SCI. The one guideline that made mention of women with SCI had significant global deficits. This highlights the importance of developing guidelines for health care providers focused specifically on women with SCI to support and optimize breastfeeding in this unique population for the benefit of mother and infant across the lifespan.

Background: Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with high production volume worldwide, which exhibit potential health risk to human. To date, little is known about the exposure of BTRs and BTHs (BTs) on human, especially in the context of pregnancy. Objectives: We aimed to characterize the exposure profiles, temporal variability, and potential predictors of urinary BTs during pregnancy. Methods: Between 2014 and 2015, we recruited 856 pregnant women in Wuhan who provided urine samples at three trimesters (13.1 ± 1.1, 23.7 ± 3.2, and 35.7 ± 3.4 gestational weeks). We measured the urinary concentrations of five BTRs (1‑H‑benzotriazole, 1‑hydroxy‑benzotriazole, xylyltriazole, tolyltriazole, 5‑chloro‑1‑H‑benzotriazole) and five BTHs (benzothiazole, 2‑hydroxy‑benzothiazole, 2‑methylthio‑benzothiazole, 2‑amino‑benzothiazole, 2‑thiocyanomethylthio‑benzothiazole) to characterize the exposure profiles of BTs. We calculated the intra-class correlation coefficients (ICCs) to assess the temporal variability and investigated potential predictors of urinary BTs by using the mixed models. Results: Most of the targeted BTs were detected in over 50% of urine samples, except for 5‑chloro‑1‑H‑benzotriazole (9.3%) and 2‑thiocyanomethylthio-benzothiazole (1.4%). The predominant BTRs in urine was 1‑hydroxy‑benzotriazole [Geometric Mean (GM): 0.77 ng/mL]. Benzothiazole was the major derivative in urine samples with a GM concentration of 1.6 ng/mL. Correlations among BTHs (r = 0.04–0.39) were higher than that among BTRs (r = 0.02–0.14). The exposure pattern was constant at low level and co-exposure to all the targeted compounds was infrequent during pregnancy. Urinary concentrations of BTRs exhibited considerable within-subject variation (ICCs: 0.12–0.56) during pregnancy. Relatively high temporal reliability was observed for urinary concentrations of BTHs with ICCs ranging from 0.42 to 0.85. It was found that parity, household income, pregnancy occupational status, sampling season and menstrual cycle were associated with urinary concentrations of BTs in pregnant women (P

OBJECTIVES/HYPOTHESIS To investigate long-term complications of newer reconstructive palate surgery techniques. STUDY DESIGN Retrospective case-series analysis. METHODS Retrospective six-country clinical study of OSA patients who had nose and palate surgery. RESULTS There were 217 patients, mean age = 43.9 ± 12.5 years, mean body mass index = 25.9 ± 4.7, mean preoperative apnea-hypopnea index [AHI] = 30.5 ± 19.1, follow-up 41.3 months. A total of 217 palatal procedures were performed, including 50 expansion sphincter pharyngoplasties (ESP), 34 functional expansion pharyngoplasties (FEP), 40 barbed reposition pharyngoplasties (BRP), 64 modified uvulopalatopharyngoplasties (mUPPP), 11 uvulopalatal flap procedures (UPF), nine suspension pharyngoplasties (SP), eight relocation pharyngoplasties (RP), and one z-pharyngoplasty (ZPP). Complications included were constant and/or felt twice per week; dry throat (7.8%), throat lump feeling (11.5%), throat phlegm (10.1%), throat scar feeling (3.7%), and difficulty swallowing (0.5%). Of the 17 patients who had a dry throat complaint, two were constant (one SP, one RP), 15 were occasional (10 mUPPP, three SP, two BRP). Of the 25 patients with the throat lump feeling, four were constant (three RP, one ZPP), 21 were occasional (10 mUPPP, five SP, five UPF, one BRP). Of the 22 patients with the throat phlegm feeling, four were constant (two SP, two RP), 18 were occasional (10 mUPPP, four BRP, two FEP, two SP). Of the eight patients with throat scar feeling, eight were occasional (four SP, two mUPPP, one FEP, one RP), none were constant. One patient had difficulty swallowing (RP procedure). There was no velopharyngeal incompetence, taste disturbance, nor voice change. Highest symptom complaints were mUPPP, SP, and RP, whereas the lowest symptom complaint was ESP. CONCLUSIONS Newer palatal techniques have shown to have less long-term complications compared to the older ablative techniques. LEVEL OF EVIDENCE 4 Laryngoscope, 130:2281-2284, 2020.

Germ cell nuclear factor (GCNF), an orphan nuclear receptor, is essential for mouse embryogenesis. GCNF specifically binds to a DR0 response element via its DNA binding domain (DBD) in vitro and functions as a repressor of gene transcription. To further study the role of GCNF during embryogenesis, we have employed a Cre/loxP strategy and generated a line of GCNF mutant mice (GCNF(lox/lox)) in which the 243-base pair DBD-encoding exon has been deleted in the germline. However, the ligand binding domain (LBD) of GCNF is still expressed at the mRNA and protein levels in the GCNF(lox/lox) mice. GCNF(lox/lox) mice die at 9.5-10.5 days postcoitum. The tailbuds of these mutant embryos protrude outside the yolk sac. Expression of Oct-4 in the somatic cells of GCNF(lox/lox) embryos at 8.25 days postcoitum was not silenced as in the GCNF(+/+) embryos. Therefore, GCNF(lox/lox) mice phenocopy the GCNF(-/-) mice. Our results indicate that the DBD is essential for the function of GCNF during early mouse embryogenesis, and that the LBD does not mediate any function independent of the DBD at this stage of embryonic development. Our results also suggest that GCNF is indeed a transcriptional factor that represses gene transcription mediated via its DBD.

Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU-domain transcription factor Oct4 (Pou5f1) during mouse post-implantation development. Although Gcnf expression is not critical for the embryonic segregation of the germ cell lineage, we found that sexually dimorphic expression of Gcnf in germ cells correlates with the expression of pluripotency-associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell differentiation, we generated an ex vivo Gcnf-knockdown model in combination with a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis and oogenesis in vivo, as well as the derivation of germ cells from embryonic stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads.

Nuclear receptor subfamily 6, group A, member 1 (NR6A1) is an orphan member of the nuclear receptor superfamily and is required for normal mouse embryonic development. In adult mice, NR6A1 is predominantly expressed in spermatogenic cells and growing oocytes of the gonads and has a role in female reproduction by modulating the transcription of the oocyte-specific genes bone morphogenetic protein 15 (Bmp15) and growth differentiation factor 9 (Gdf9). In our goal to further understand the functional role of NR6A1 during postnatal development, we generated a Nr6a1:beta-galactosidase (LacZ) knockin reporter (Nr6a1(LacZ/+)) mouse line in which the Nr6a1:LacZ fusion gene was expressed and then characterized Nr6a1 expression in these reporter mice by performing LacZ staining. Our RT-PCR analyses showed that Nr6a1 was expressed in a variety of somatic tissues (e.g., oviduct and lung) other than gonads of normal adult mice. In adult Nr6a1(LacZ/+) mice, robust LacZ staining was observed in the gametes of gonads. Strong positive LacZ staining was also observed in the sperm of the epididymis, epithelial cells of the oviduct, and bronchioles within the lung. In adult Nr6a1(LacZ/+) mice, positive LacZ staining was observed in other somatic tissues, including hippocampus, cerebral cortex, cerebellum, and thalamus of brain; pars intermedia and pars anterior of pituitary; parathyroid; and islet of pancreas. NR6A1 expression in sperm within the epididymis, epithelial cells in the oviduct, and bronchioles of the lung was further confirmed by immunohistochemical studies. Nr6a1 is expressed not only in the germ cells of mouse gonads but also in a variety of somatic tissues, including epididymis, oviduct, brain, and pituitary. The extra-germ cell expression of NR6A1 makes it a less attractive contraceptive.

Choroid plexus papilloma (CPP) arising in the temporal horn is rare in adult population, and to the best of our knowledge, there has been no report of such a case with temporal lobe epilepsy (TLE). The authors describe a unique case of a 27-year-old woman who was diagnosed as TLE and was found to have a CPP in the temporal horn. Choroid plexus papilloma of the temporal horn, even though rare, can be found in adult population and be causally related to temporal lobe epilepsy.

Sclerosing meningioma is a rare morphologic subtype of meningioma and may be mistaken for atypical or malignant meningioma and astrocytoma or schwannoma because of marked collagen deposits and a sparse population of cells with little resemblance to meningothelial cells. Authors describe the histopathologic and immunophenotypic features of five cases of sclerosing meningioma. Histologically, all the cases consisted of paucicellular collagenous tissue containing spindle cells with or without small foci of meningothelial cell proliferation. The morphology and immunohistochemical profile of the spindle cells were different from those of conventional meningothelial cells. The meningothelial cells showed a typical immunoreactivity of conventional meningiomas, while the spindle cells displayed a strong expression of vimentin. The Ki-67 labelling index was uniformly low in all cases, and none of cases expressed p53 protein. In summary, the recognition of meningothelial cells in massively sclerotic lesions is helpful for a correct diagnosis. In the cases with a total absence of meningothelial cells, however, the vague collagenous whorls are more diagnostic rather than immunohistochemistry. Considering association with clear cell meningioma, prospective and retrospective long-term follow-up is necessary for deciding whether reminiscent clear cell meningiomas should be separated from sclerosing meningioma or not.

The majority of primary central nervous system lymphomas (PCNSL) are of B cell origin, and those of T cell origin are a distinct rarity. Furthermore, spinal cord involvement of T cell PCNSL is extremely rare and only a small number of cases have been reported. The authors report a case of multifocal T cell PCNSL mainly involving the intramedullary (IM) portion ofthe spinal cord in a 57-year-old woman. Neurological examination showed right leg weakness and hypesthesia below the T10 level. Magnetic resonance images revealed multiple well enhancing masses in the IM portion ofthe cervical and thoracic spinal cord and the cerebellum. Cytological examination of the cerebrospinal fluid revealed no malignant cells. As the mass at the C7 level was the largest among multiple masses, open biopsy was performed at that level. Histopathological examination confirmed malignant peripheral T cell lymphoma, unspecified (PTCL-U), small- and medium-sized cell type. Clinical and laboratory investigations failed to reveal any evidence of lymphomatous deposits elsewhere in the body. After biopsy, the patient received cranio-spinal irradiation, which included the whole brain and the spinal neuraxis. The clinical course, pathological findings and treatments are discussed and a review of the literature included.

Intramedullary spinal cord astrocytomas are relatively rare and usually low-grade lesions with a long natural history. The rarity of the condition and its indolent clinical course has made the evaluation of treatment efficacy difficult. To clarify postoperative outcome and prognostic factors, we performed a retrospective analysis of intramedullary spinal cord astrocytomas in a single institute. Twenty-eight patients were surgically treated between 1978 and 1999; of median age 36 years (range, 19-68 years); nineteen patients were males and nine females. All patients presented with pain and neurological deficits. The cervical cord was involved in fifteen patients, cervico-thoracic in five, thoracic in six and thoraco-lumbar in two. Gross total removal was performed in three patients, subtotal removal in six, partial removal in fourteen and biopsy only in five. Nineteen patients received radiation therapy postoperatively. The mean follow-up period was 31.9 months (range, 0.5-184 months). Low-grade astrocytomas were found in 18 cases, anaplastic astrocytoma in three cases and glioblastomas in seven cases. The median survivals of patients with low- and high-grade astrocytoma were 184 months and 8 months, respectively (p0.05). The median survivals of irradiated and non-irradiated patients with low-grade astrocytoma were 184 months and 102 months. Neither the extent of resection, nor radiation influenced the survival rate. In summary, the histological grade was the most significant predictor of survival in patients with astrocytoma of the spinal cord.

In order to elucidate the radiological features of dysembryoplastic neuroepithelial tumor (DNT), and to clarify the optimal surgical strategy for this tumor, the authors retrospectively analyzed 20 cases of DNT treated at our institution. Magnetic resonance (MR) imaging (all cases), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) (eight cases), ictal/interictal Tc99m-HMPAO single photon emission computed tomography (SPECT) (seven and five cases respectively) and proton magnetic resonance spectroscopy (1H MRS) (one case) were performed preoperatively. Invasive monitoring/intraoperative electrocorticography (ECoG) was performed in four cases in order to determine the epileptogenic zone. A well-demarcated lobulating tumor located in the cortical with/without subcortical area was the typical MR finding. 18F-FDG PET showed glucose hypometabolism in all cases. Ictal Tc99m-HMPAO SPECT showed hyperperfusion of the lesion in three cases and interictal Tc99m-HMPAO SPECT showed hypoperfusion of the lesion in one case. 1H MRS showed nonspecific findings. Gross total resection was performed in all cases. Histologically, associated cortical dysplasia was found in 11 cases. The mean duration of follow-up after surgery was 37.9 months, and the overall seizure free rate was 90%. Follow-up MR imaging was performed in 14 cases (mean duration of follow-up: 21.6 months) and showed no recurrence of tumor in any of these cases. Invasive monitoring/intraoperative ECoG and the presence of cortical dysplasia showed no significant relationship with seizure control rate (p = 1.25 and p = 1.62 respectively).

MR imaging, PET, and ictal SPECT have been studied extensively as individual techniques in the localization of epileptogenic foci, but only a few comparative studies have been done. We evaluated the concordance rates of ictal video/EEG, MR imaging, PET, and ictal SPECT to compare the sensitivities of these imaging methods in the lateralization of epileptogenic foci.The study included 118 consecutive patients who underwent surgery for medically intractable epilepsy and who were followed up for 12 months or more. MR imaging was compared retrospectively with ictal video/EEG, FDG-PET, ictal 99mTc-HMPAO SPECT, and invasive EEG as to their ability to localize the epileptogenic focus; the pathologic findings served as the standard of reference.MR imaging was concordant with video/EEG, PET, and ictal SPECT in 58%, 68%, and 58% of patients, respectively. With the pathologic diagnosis as the standard of reference, MR imaging, PET, and ictal SPECT correctly lateralized the lesion in 72%, 85%, and 73% of patients, respectively. Of the patients with good outcomes, MR imaging, PET, and ictal SPECT were correct in 77%, 86%, and 78%, respectively. In the good outcome group, MR imaging was concordant with PET and ictal SPECT in 73% and 62% of patients, respectively. Of 45 patients who underwent invasive EEG, MR imaging was concordant with the invasive study in 47%; PET in 58%; and ictal SPECT in 56%. Of 26 patients with normal MR findings, PET and ictal SPECT correctly lateralized the lesion in 80% and 55%, respectively.Overall concordance among the techniques is approximately two thirds or less in lateralizing epileptogenic foci. PET is the most sensitive, even though it provides a broad approximate nature of the epileptogenic zone, which is not adequate for precise surgical localization of epilepsy. PET and/or ictal SPECT may be used as complementary tools in cases of inconclusive lateralization with ictal video/EEG and MR imaging.

We report a rare case of thoracic intramedullary schwannoma. The patient, a 37-year-old woman, showed no evidence of neurofibromatosis. The possible etiology and treatment of the tumor are discussed and a review of literature is presented.

The pluripotent factor Oct4 is a key transcription factor that maintains embryonic stem (ES) cell self-renewal and is down-regulated upon the differentiation of ES cells and silenced in somatic cells. A combination of cis elements, transcription factors, and epigenetic modifications, such as DNA methylation, are involved in the regulation of Oct4 gene expression. Here we show that the orphan nuclear receptor GCNF initiates Oct4 repression and DNA methylation by the differential recruitment of MBD (methylated CpG binding domain) factors to the promoter. Compared with wild-type ES cells and gastrulating embryos, Oct4 repression is lost and its proximal promoter is significantly hypomethylated in RA-differentiated GCNF−/− ES cells. The Oct4 gene is reexpressed in some somatic cells of GCNF−/− embryos, showing that it has not been properly silenced coincident with reduced DNA methylation of its promoter. Efforts to characterize mediators of GCNF's repressive function and DNA methylation of the Oct4 promoter identified methyl-DNA binding proteins, MBD3 and MBD2, as GCNF-interacting factors. In P19 and ES cells, upon differentiation, endogenous GCNF binds to the Oct4 proximal promoter and differentially recruits MBD3 and MBD2. In differentiated GCNF−/− ES cells, recruitment of MBD3 and MBD2 to the Oct4 promoter is lost, and repression of Oct4 expression and DNA methylation fails to occur. RNA interference-mediated knockdown of MBD3 and/or MBD2 expression results in reduced Oct4 repression in differentiated P19 and ES cells. Repression of Oct4 expression and recruitment of MBD3 are maintained in de novo DNA methylation-deficient ES cells (Dnmt3A/3B-null cells), while MBD2 recruitment is lost. Thus, recruitment of MBD3 and MBD2 by GCNF links two events, gene-specific repression and DNA methylation, which occur differentially at the Oct4 promoter. GCNF initiates the repression and epigenetic modification of Oct4 gene during ES cell differentiation.

Records of 106 patients with squamous cell carcinoma of the larynx treated with radiation therapy (RT) at Washington Adventist Hospital between 1976 and 1988 were analyzed for patterns of failure and survival, with a minimum of five-year follow-up. In patients treated with RT alone, initial local control rate was 72% for tumors involving supraglottic larynx and 90% for glottic larynx; in postoperative RT patients, the rate was 65% in the supraglottic and 67% in the glottic larynx group. The laryngeal preservation rate in patients treated with RT alone was 87% in those with early lesions (T1 and T2) and 63% in those with advanced tumors (T3 and T4). The overall five-year determinate survival rates of the RT-only group and the postoperative RT group were 90% and 57%, respectively. In patients with advanced tumors (stages III and IV), survival rates were comparable for RT alone and postoperative RT (56% and 52%, respectively).

Twenty-two patients with advanced laryngeal cancer and 5 with advanced pyriform sinus cancer were given 51 Gy (5,100 rad) followed by surgical resection. In 10 (45 %) of patients with laryngeal cancer, no tumor was found at the primary site pathologically; 15 (68%) had negative neck specimens. All of those with pyriform sinus cancer had positive specimens. Eighteen patients with laryngeal cancer are free of disease. In contrast, only 1 with pyriform sinus cancer is free of disease; 1 has had a local recurrence and 3 have had metastases. The data suggest that 51 Gy (5,100 rad) are insufficient to sterilize pyriform sinus cancer; higher doses together with adjuvant chemotherapy are needed.

Thirty-five patients who were to undergo radiotherapy and 13 normal subjects were evaluated with taste questionnaires, taste acuity tests, and plasma zinc analyses. The studies were repeated on the patients in the fifth week of radiotherapy. The mean taste thresholds for NaCl (salt), sucrose (sweet), HCl (sour), and urea (bitter) were elevated and the plasma zinc levels were lower (77.2 +/- 11.8 vs. 94.6 +/- 30.1 g/100 ml, p = 0.055) for the patients than for the controls. However, there was not a significant correlation between the taste thresholds and plasma zinc levels at any time. The mean weight loss experienced by the 14 patients who reported subjective taste alteration in the fifth week was 3.1 kg versus 0.1 kg (p = 0.005) for those who did not report taste alteration. The data suggest that alterations in taste acuity, but not plasma zinc levels, are associated with weight loss during radiotherapy.

A histologic grading system based on tumor differentiation was applied in a study of 122 patients with stage IB and IIA squamous cell carcinoma of the uterine cervix. In general, the more dedifferentiated the primary tumor, the more bulky the primary lesion and the higher the incidence of pelvic node metastasis. Following treatment, patients with undifferentiated tumors had a higher incidence of tumor recurrence a lower 2-year survival rate than those with well or moderately differentiated lesions. These findings suggest that histologic grading is an important adjunct to the clinical evaluation of cervical cancer.

Thirty-three patients were randomized prior to pelvic radiotherapy to receive the bile acid-sequestering resin colestipol hydrochloride, 5 grams qid, during the entire time of their therapy or diphenoxylate hydrochloride and atropine sulfate 2.5-20 mg per day (control) if they experienced diarrhea. The colestipol patients also took diphenoxylate if they had diarrhea. The patients in the colestipol group often experienced nausea, vomiting, and abdominal cramps and 8 were forced to discontinue the drug. There was no difference in the weekly stool frequency between the colestipol and the control patients but the colestipol patients who took at least 50% of the prescribed dose required fewer diphenoxylate tablets than the controls. The data suggest that colestipol hydrochloride is not of value in preventing radiation-induced diarrhea because of the side effects associated with the drug, but the theory on which the use of bile acid-sequestering agents is based may be correct.