Effect of wearing masks on odor detection and recognition.

BACKGROUND: The effect of wearing masks on olfaction remains unclear. OBJECTIVES: This study aimed to clarify the differences between the effects of no masks, surgical masks, and N95 respirator masks by conducting both identification and threshold olfaction tests. METHODS: Young, healthy volunteers aged ≥ 18 years and < 30 years without awareness of apparent olfactory disorder were included. All participants filled out a questionnaire on olfaction and completed an acuity smell identification test (Open Essence test) and an olfactory threshold test (T&T olfactometry) while wearing no masks, surgical masks, or N95 respirator masks. RESULTS: In the Open Essence tests, the no-mask group score was significantly higher than those of the surgical- and N95-mask groups. Using T&T olfactometry, the median-detection threshold of the no-mask group was significantly lower than that of the surgical-mask group, and the surgical-mask group threshold was significantly lower than that of the N95-mask group. Similar patterns were observed for the median-recognition threshold. CONCLUSIONS: Wearing masks, especially an N95 mask, reduces the ability to detect and identify odors. This disadvantage should be considered by professionals such as healthcare workers, who require proper olfaction to perform appropriate tasks.

A novel extraperitoneal cesarean section of supravesical approach: Operative techniques.

AIM: We have established a novel extraperitoneal cesarean section technique by supravesical approach. An advantage of this technique over the conventional paravesical approach is that the lower uterine segment is broadly exposed and that all operative procedures can be performed under direct vision. We present the details of this novel technique. METHODS: The bladder and the peritoneum are exposed by removing the transversalis and extraperitoneal fasciae. Subsequently, a triangular area between the median umbilical ligament, the peritoneum, and the bladder is exposed. The median umbilical ligament is dissected at this site. Bladder dissection from the peritoneum is also initiated from this area and proceeds toward the lower uterine segment. RESULTS: Operative times for pelvic fascia dissection and bladder removal from the peritoneal surface are currently around 15-25 min. During the process of development of this technique, there have been no bladder injuries in 501 patients that caused urine leakage. DISCUSSION: The supravesical approach has been considered difficult due to the strong adhesion between the perivesical fascia and the peritoneum at the bladder fundus. In this paper, we show how to safely remove the bladder fundus from the peritoneum. The bladder can then be easily lowered down toward the lower uterine segment. Although this technique allows the lower uterine segment to be broadly exposed and all operative procedures can be performed under direct vision, a disadvantage is the comparatively long time currently required to perform it. CONCLUSIONS: This technique could be a valuable option for extraperitoneal cesarean section, but disadvantages must also be considered.

Fatty acid binding protein type 7 deficiency preserves auditory function in noise-exposed mice.

Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.

The Transition of Pediatric Tracheobronchial Foreign Body Cases in the Past 36 Years: A Retrospective Single-Center Study in Japan.

Tracheobronchial foreign bodies (TFBs) are pediatric airway emergencies frequently seen. We aimed to examine the changes in the clinical characteristics of pediatric TFB patients in a single institution within the past 36 years. We retrospectively reviewed the data of 85 patients aged 0-10 years with TFBs lodged in the trachea or bronchus admitted at the Department of Otolaryngology-Head and Neck Surgery at Tohoku University Hospital between 1986 and 2021. We also compared the characteristics, diagnostic methods, and treatments of the previous 64 cases (1986-2005) with those of the recent 21 cases (2006-2021). The number of TFB patients decreased later in this study (3.2 vs. 1.3 patients per year). The proportion of TFB patients aged > 3 years was significantly higher in the later period (6.3% vs. 23.8%, p = 0.038). Peanut was the most common cause of TFBs in both periods, and the overall incidence of peanut aspiration significantly decreased in the later period (68.8% vs. 38.1%, p = 0.019). No patient had an undetected TFB for more than 1 month after the onset of symptoms in the later period. Foreign body extraction using rigid bronchoscopy was performed in all patients earlier, whereas flexible bronchoscopy was used in 14.3% later. Our study revealed a recent trend in the clinical characteristics of pediatric TFB patients in a single institution in Northeast Japan. The prevention and treatment of pediatric TFBs should be considered following the recent trends.

Colporrhaphy using elastic tissue continuous with and obscured behind the fibromuscular layer of the vaginal wall.

AIM: Due to the U.S. Food and Drug Administration's order to cease the use of surgical mesh for transvaginal repair, an improvement of the native tissue repair (NTR) of pelvic organ prolapse (POP) could become important as one of the first-line operative methods. This study details the surgical technique of an NTR method we developed, with report of our 5 years of experience. METHODS: Operative technique: A new fibromuscular layer (FL) was constructed using a thick and elastic tissue continuous with and obscured behind the original FL of the vaginal wall. PATIENTS: Between April 2017 and March 2020, we performed our novel repair technique on 87 women with POP of either quantification stage III or IV. RESULTS: We followed up 80 of the 87 women for over 24 months up to 60 months (follow-up rate: 91.2%). POP recurred (defined as stage II or higher) in four patients (5.0%). Operation time was 49-70 min. The bleeding volume was 70-250 g. There were no intra- or postoperative complications that required further treatment. CONCLUSIONS: This procedure could potentially become one of the first-line operative methods for repairing POP.

Establishment of Neh2-Cre:tdTomato reporter mouse for monitoring the exposure history to electrophilic stress.

Cells are often exposed to exogenous and endogenous redox disturbances and exert their protective mechanisms in response to stimuli. The KEAP1-NRF2 system plays pivotal roles in counteracting oxidative damage. Due to the transient nature of NRF2 activation, the identification of cells in which NRF2 is activated in response to systemic stimuli is sometimes not easy. To examine the electrophilic stress response at a single-cell resolution, we aimed to develop a new reporter mouse in this study. A cell-tracing strategy exploiting Cre recombinase-mediated activation of a reporter gene was chosen for stable detection of reporter expression instead of real-time monitoring of the cellular response. We established a transgenic mouse line expressing the Neh2-Cre recombinase fusion protein. As Neh2 is an amino-terminal domain of NRF2 that serves as a degron and mediates KEAP1-dependent degradation and electrophile-inducible stabilization, Neh2-Cre was expected to be activated in response to electrophiles. The Neh2-Cre transgenic mouse was crossed with the ROSA26-loxP-stop-loxP-tdTomato reporter mouse (ROSA-LSL-tdTomato mouse). The compound mutant reporter mice exhibited accumulation of tdTomato-positive cells in various organs after repeated administration of CDDO-Im, one of the NRF2-inducing electrophiles. The mice were also successfully used for the detection of cells that experienced a cisplatin-induced electrophilic stress response.

Activation of the NRF2 pathway in Keap1-knockdown mice attenuates progression of age-related hearing loss.

Age-related hearing loss (AHL) is a progressive sensorineural hearing loss in elderly people. Although no prevention or treatments have been established for AHL, recent studies have demonstrated that oxidative stress is closely related to pathogenesis of AHL, suggesting that suppression of oxidative stress leads to inhibition of AHL progression. NRF2 is a master transcription factor that regulates various antioxidant proteins and cytoprotection factors. To examine whether NRF2 pathway activation prevents AHL, we used Keap1-knockdown (Keap1FA/FA) mice, in which KEAP1, a negative regulator of NRF2, is decreased, resulting in the elevation of NRF2 activity. We compared 12-month-old Keap1FA/FA mice with age-matched wild-type (WT) mice in the same breeding colony. In the Keap1FA/FA mice, the expression levels of multiple NRF2 target genes were verified to be significantly higher than the expression levels of these genes in the WT mice. Histological analysis showed that cochlear degeneration at the apical and middle turns was ameliorated in the Keap1FA/FA mice. Auditory brainstem response (ABR) thresholds in the Keap1FA/FA mice were significantly lower than those in the WT mice, in particular at low-mid frequencies. Immunohistochemical detection of oxidative stress markers suggested that oxidative stress accumulation was attenuated in the Keap1FA/FA cochlea. Thus, we concluded that NRF2 pathway activation protects the cochlea from oxidative damage during aging, in particular at the apical and middle turns. KEAP1-inhibiting drugs and phytochemicals are expected to be effective in the prevention of AHL.

Potential effect of intravenous immunoglobulin against paraneoplastic cerebellar degeneration in progressive ovarian cancer.

We report the effect of intravenous immunoglobulin (IVIG) against paraneoplastic cerebellar degeneration (PCD) in a case of progressive ovarian cancer. Our patient developed PCD soon after postoperative chemotherapy and became bedridden. After undergoing IVIG, however, symptoms dramatically improved, and unexpectedly the remaining tumors were confirmed to have completely disappeared. When PCD is diagnosed, IVIG treatment should be attempted to reduce neuropathy regardless of its degree and the state of the cancer. It may also have further potential benefits that should be considered.

Author Correction: Nrf2 contributes to the weight gain of mice during space travel.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nrf2 contributes to the weight gain of mice during space travel.

Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans.

Malignant Lymphoma of the Ovary: A Diagnostic Pitfall of Intraoperative Consultation.

Primary ovarian lymphomas are rare, but can potentially evoke diagnostic problems. We present a case of ovarian lymphoma, in which an ambiguous intraoperative pathologic report led to overtreatment (unnecessary surgery). A 73-yr-old woman with fatigue and low-grade fever was diagnosed as having a left ovarian tumor by imaging modalities. Exploratory laparotomy was carried out to confirm the diagnosis. The frozen tissue sections of the ovarian tumor showed condensed proliferation of atypical round cells accompanied with a few small lymphocytes. The pathologists could not determine whether this tumor was a lymphoma or another malignancy (eg, dysgerminoma). Hence, they reported it to gynecologists who operated as simply a malignant tumor in order to evade misdiagnosis. On the basis of the inconclusive pathologic report, the gynecologists decided to change the planned laparotomy to total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. A postoperative paraffin section-based pathologic diagnosis was diffuse large B-cell lymphoma of the ovary, which basically does not require surgical treatments. Subsequently, chemotherapy for B-cell lymphoma was initiated, and no lymphoma recurrence has been reported to date. A more robust preoperative discussion between the gynecologists and the pathologists might have avoided the overtreatment.

Gastric-type endocervical adenocarcinoma with uterine corpus involvement mimicking primary endometrial carcinoma.

Differentiation of endocervical adenocarcinomas involving the uterine corpus from primary endometrial (EM) carcinomas involving the cervix is, not only clinically but also pathologically, often difficult. We report a case of gastric-type endocervical adenocarcinoma involving the corpus that could be correctly diagnosed because it was a unique endocervical adenocarcinoma subtype. A 69-year-old woman who presented with abnormal genital bleeding was diagnosed as having a uterine adenocarcinoma on pathological examination of EM biopsy. Preoperative imaging findings and a surgical specimen showed that the tumor was mainly located in the corpus and involved the cervix. We considered at first that the tumor was an EM adenocarcinoma invading into the cervix. However, results of an immunohistochemical examination indicated that it was a gastric-type mucinous adenocarcinoma derived from the endocervix. Our final pathological diagnosis was a gastric-type endocervical adenocarcinoma spreading to the uterine corpus.

Bleeding in the retroperitoneal space under the broad ligament as a result of uterine perforation after dilatation and curettage: Report of a case.

Uterine perforation, a complication of dilation and curettage, is typically recognized immediately after the procedure by clinical symptoms of peritoneal irritation resulting from intraperitoneal bleeding. Our patient complained of having an uncomfortable feeling, slight dizziness, palpitation in the sitting position and abdominal discomfort but did not show signs of peritoneal irritation 24 h after dilation and curettage. However, she suddenly complained of abdominal pain. Tenderness and rebound tenderness were detected at the lower abdominal wall. Ultrasonography and magnetic resonance imaging suggested uterine perforation. When the abdominal cavity was opened, a hematoma under the broad ligament of the uterus, laceration of the side wall of the uterine cervix and a small amount of bloody ascites and small clots in the abdominal cavity were observed. The uterine cervical wall was sutured. Physicians should postpone discharge and observe the clinical course carefully when a patient complains of inexplicable discomfort after dilation and curettage.

Determination of low-level radiostrontium, with emphasis on in situ pre-concentration of Sr from large volume of freshwater sample using Powdex resin.

An improved analytical method was developed for determining of low levels of radiostrontium in environmental freshwater samples. Emphasis was placed to the in situ pre-concentration of radiostrontium with Powdex resin in large volumes (100-300 L) of freshwater samples from many locations without using of deleterious substances such as NaOH and mineral acids. Measuring electric conductivity (EC) of water samples enabled the estimation of the amount of Powdex resin required for quantitative recovery of Sr from the large water samples in the field. The Powdex resin that adsorbed Sr was brought back to the laboratory, and Sr adsorbed in the resin was eluted by 8 M HNO3 together with Sr carrier added. Strontium was radiochemically separated by the cation exchange method for ß counting after removal of most of the Ca using Ca(OH)2 precipitation. Through the procedure the Sr chemical yield was 88% on average. This analytical method was verified by analyzing 170 L of water samples with different salinity values, to which a known amount of (90)Sr was added. The detection limits of (90)Sr activities obtained using the 170 L water samples was estimated to be approximately 0.1 mBq L(-1) for a counting time of 100 min. The method was also applied to environmental samples collected from Ibaraki and Fukushima prefectures; their (90)Sr activities ranged from 0.16 to 0.93 mBq L(-)(1).

Cardiac tamponade in pregnancy during the treatment of severe pre-eclampsia: report of a case.

We present a case of cardiac tamponade that occurred during the course of treatment for severe pre-eclampsia. A 37-year-old woman who underwent cesarean section for severe pre-eclampsia developed cardiac tamponade after delivery. While percutaneous pericardiocentesis temporarily improved her condition, pericardial effusion, dyspnea and tachycardia reappeared 5 days after delivery. A continuous drainage tube placed in the pericardial cavity for 5 days was required to maintain maternal cardiac function. Her clinical course was uneventful after continuous drainage and she was discharged 20 days after delivery. No such causes of symptomatic pericardial effusion were detected in the present case. Physicians should be aware of this complication when dyspnea is accompanied by tachycardia and enlargement of the cardiac silhouette with hypolucent lungs on chest X-ray. Immediate pericardiocentesis is also required to prevent life-threatening cardiac tamponade in such cases.

Adenocarcinoma arising from vaginal stump: unusual vaginal carcinogenesis 7 years after hysterectomy due to cervical intraepithelial neoplasia.

Primary vaginal adenocarcinomas are one of the rarest malignant neoplasms, which develop in the female genital tract. Because of the extremely low incidence, their clinical and pathologic characteristics are still obscure. Recently, we experienced a case of vaginal adenocarcinoma that appeared 7 yr after hysterectomy because of cervical intraepithelial neoplasia. The patient, a 65-yr-old obese woman, was diagnosed as having adenocarcinoma in the vaginal stump and was treated by simple tumor excision and radiation. Immunohistochemical and molecular biologic examinations indicated a potential association with human papilloma virus infection in the development of the vaginal adenocarcinoma. There has been no evidence of recurrence for 3 yr after the operation.

Morphological and flow cytometric analysis of cell infiltration in glioblastoma: a comparison of autopsy brain and neuroimaging.

Even when we successfully perform a total extirpation of glioblastoma macroscopically, we often encounter tumor recurrence. We examined seven autopsy brains, focusing on tumor cell infiltration in the peripheral zone of a tumor, and compared our findings with the MR images. There has so far been no report regarding mapping of tumor cell infiltration and DNA histogram by flow cytometry, comparing the neuroimaging findings with the autopsy brain findings. The autopsy brain was cut in 10-mm-thick slices, in parallel with the OM line. Tissue samples were obtained from several parts in the peripheral zone (the outer area adjacent to the tumor edge as defined by postcontrast MRI) and then were examined by H&E, GFAP, and VEGF staining. We defined three infiltrating patterns based on number of infiltrated cells as follows: A zone, 100%-60% of the cells infiltrated tumor cells compared with tumor cell density of the tumor mass; B zone, 60%-20%; C zone, 20%-0%. In the autopsy brain, the tumor was easily identified macroscopically. We found that (1) the tumor cells infiltrated the peritumoral area; and (2) tumor cell infiltration was detected over an area measuring from 6 to 14 mm from the tumor border in the A zone. When performing surgery on glioblastoma, a macroscopic total extirpation of the tumor as defined by the contrast-enhanced area in MRI is therefore considered to be insufficient for successfully reducing tumor recurrence.

Flow cytometric analysis for the mechanism of the new antineoplastic agent temozolomide in glioma cells.

Temozolomide (TMZ) has been accepted as a standard antitumor drug for glioma worldwide. Regarding its mechanism of action, there are quite a few analyses. In the present study, we investigated the cell-killing effect and mechanism of action of TMZ with flow cytometry using glioblastoma cell lines. Each cell line was divided into three groups: a control group, a low-dose TMZ group, and a high-dose TMZ group. On day 1, TMZ was added to each cell line. Then, we counted the numbers of cells on days 2, 3, 4, and 5; in U87MG, we counted the number of cells on days 8 and 9. Simultaneously, we performed flow cytometric analysis with single- and double-staining methods. Although results varied slightly depending on the cell line, with flow cytometric analysis we identified the G(0)G(1)-, S-phase block on days 2 through 4, at the beginning of TMZ administration. After that we identified the deviation of the G(2)M block over days 3 to 5. Dominant morphological changes observed in U87MG were confined to the nuclei, with positive TUNEL staining. Early S-phase block and then a G(2)M block were observed; consecutively, we could analyze these blocks with a double-staining method more clearly. The flow cytometric method is very effective in the analysis of the antitumor mechanism of each agent. On the basis of our analysis, more effective combined chemotherapy may be expected.

Interleukin-5 and interleukin-10 are produced in central nervous system tumor cysts.

Interleukin-5 and interleukin-10, as important mediators of vascular permeability, contribute to the development of various pathologic effusions. However, little is known regarding the involvement of these two cytokines in the formation of cysts associated with central nervous system (CNS) tumors. Twenty-eight patients with various cystic CNS tumors were investigated for expression of interleukin-5 and interleukin-10 in cyst fluid and their matched cytokine receptors in tumor tissue. Interleukin-5 and interleukin-10 were detected in cyst fluid, and interleukin-5 concentration was significantly correlated with interleukin-10 concentration (r=0.508, p=0.006). Moreover, both receptors were also detectable in the tumor tissue specimens and high levels of expression were also found in perivascular cells. Therefore, the local production of interleukin-5 and interleukin-10 might be implicated in some types of cyst formation.

An immunohistochemical and electron microscopic study of atypical teratoid/rhabdoid tumor.

We report two infant cases with atypical teratoid/rhabdoid tumor (AT/RT) located in the cerebellar vermis and spinal cord. MRI showed the tumors were isointense on T1-weighted images and mixed intensity of isointense and slight high intensity on T2-weighted images. Postcontrast MRI demonstrated clear margin of tumor and heterogeneous strong enhancement. It was difficult to differentiate the tumor from medulloblastoma by hematoxylin and eosin staining. However, immunohistochemical staining showed that these tumor cells react positively for cytokeratin, smooth muscle actin (SMA), and epithelial membrane antigen (EMA) and helped us with the differentiation. Electron microscopic study has confirmed the presence of mesenchymal components, such as filaments and desmosome junctions in the rhabdoid cells, but no neuronal components. The tumors rapidly increased in size, showing high MIB-1 index, and the prognosis was gave.