Initiation of peritoneal dialysis in a patient with chronic renal failure associated with tetralogy of Fallot: a case report.

BACKGROUND: Tetralogy of Fallot is the most common cyanotic congenital heart disease. Patients with the condition have a high risk of developing chronic kidney disease. Treatment of kidney disease in patients with complex hemodynamics presents unique challenges. However, there are very few reports on the treatment of end-stage renal failure in patients with tetralogy of Fallot. CASE PRESENTATION: We present a rare case of peritoneal dialysis in a 47-year-old man with tetralogy of Fallot who had not undergone intracardiac repair. Peritoneal dialysis successfully removed fluids and solutes without adversely affecting the patient's hemodynamics. Our patient was managed with peritoneal dialysis for 5 years before he succumbed to sepsis secondary to digestive tract perforation. CONCLUSIONS: In this paper, we discuss the importance of monitoring acid-base balance, changes in cyanosis, and hyperviscosity syndrome during peritoneal dialysis in patients with tetralogy of Fallot. Lower leg edema and B-type natriuretic peptide level were useful monitoring parameters in this case. This case illustrates that with attention to the patient's unique requirements, peritoneal dialysis can provide successful renal replacement therapy without compromising hemodynamics in patients with tetralogy of Fallot.

De Novo Synthesis of Possible Candidates for the Inagami-Tamura Endogenous Digitalis-like Factor.

De novo synthesis of possible candidates for the Inagami-Tamura endogenous digitalis-like factor (EDLF) was achieved to validate a previously proposed structure. Our synthetic approach involves a highly regio- and diastereoselective Mizoroki-Heck reaction and a Friedel-Crafts-type cyclodehydration to construct steroidal tetracycle 14 as a versatile common intermediate leading to seven 2,14ß-dihydroxyestradiol analogues 1a-c, 2a-c, and 3 as possible candidates. By comparing the potency of inhibitory activity against Na+/K+-ATPase between the synthesized candidates and the EDLF, it was found that the proposed structure is not likely to be a true structure of the Inagami-Tamura EDLF.

[Preoperative evaluation of surgery for intractable aspiration based on the prognostic nutritional index].

Because there is no absolute indicator of the nutritional status and prognosis in patients with severe aspiration problems, it is quite difficult to arrive at a true long-time prognosis. By performing surgery for intractable aspiration on such patients, both the prognosis and QOL of the patients could be expected to improve. In our department, we have experienced patients dying within 6 months after surgery. In these cases, the patient's preoperative nutritional status was not good. Therefore, we consider that, when we adopt this procedure, there should be some indicators we should use which could have an effect on the prognosis of such nutritionally-challenged patients. In patients who underwent surgery for intractable aspiration; we examined the relationship between their survival and the prognostic nutritional index (PNI) which is an indicator of the risk of complications such as post-operative events in the surgical field. We investigated the relationship between the prognosis and the postoperative indicators of each of the following: WBC, CRP, serum albumin level, and PNI. Out of a total of 31 cases, the average O-PNI of eight cases in which death occurred was 29.45, and the average of six cases in which death occurred within 6 months after surgery was 28.26. The average O-PNI of the survivors was 36.01. A significant association was noted between the early postoperative deaths and some of the four indicators namely that serum albumin level and O-PNI. Based on the ROC curve, the O-PNI offered higher precision than the albumin level. The cut-off value of the O-PNI value for early postoperative mortality rate was 32. The early postoperative mortality rate was 44.4% in patients with less than 32 O-PNI in the preoperative examination, but if it were O-PNI 32 or more, the early postoperative mortality rate was 9.1%, significantly lower. Therefore, O-PNI could be useful as one of the prognostic evaluation factors in the case of preoperative surgery for intractable aspiration. Based on the O-PNI score, it was possible to evaluate the survival benefit associated with this operative procedure. We showed a treatment algorithm based on the preoperative O-PNI value. We believe there is a necessity to develop preoperative effective nutritional therapy as a future issue.

Transient Receptor Potential Ankyrin 1 Channel Alters Transforming Growth Factor Beta 1/Smad Signaling in Rat Vocal Fold Fibroblasts.

OBJECTIVES: Vocal fold scar remains a therapeutic challenge. Vocal fold fibroblasts (VFFs) secrete extracellular matrix (ECM), and transforming growth factor-beta 1 (TGF-ß1)-mediated fibroblast to myofibroblast differentiation is central to the development of fibrosis. The transient receptor potential (TRP) channel superfamily is a group of nonselective cation channels, and activation of TRP ankyrin 1 (TRPA1) channel has been shown to have antifibrotic effects through TGF-ß1/Smad signaling in various organs. This study aimed to elucidate expression of TRPA1 and the impact of TRPA1 activation on TGF-ß1/Smad signaling in VFFs. METHODS: Vocal folds were dissected from 10-week-old, male Sprague-Dawley rats and primary VFFs were established. TRPA1 was examined in VFFs and lamina propria via immunostaining. VFFs were treated with allyl isothiocyanate (AITC, TRP channel agonist, 10-5 M) ± TGF-ß1 (10 ng/ml) ± A-967079 (selective TRPA1 channel antagonist, 5.0 × 10-7 M) for 4 or 24 h. Trpa1, Smad3, Smad7, Col1a1, Acta2, and Has1 mRNA expression were quantified via qPCR. RESULTS: TRPA1 was expressed in cultured VFFs and the lamina propria. TGF-ß1 administration significantly increased Trpa1 compared to control. AITC alone did not alter Smad3, Smad7, Acta2, or ECM related genes. However, the combination of AITC and TGF-ß1 significantly increased Smad3 and decreased Smad7 and Acta2 compared to TGF-ß1 alone; A-967079 significantly reduced this response. CONCLUSIONS: VFFs expressed TRPA1, and the activation of TRPA1 regulated TGF-ß1/Smad signaling in VFFs. These findings provide preliminary insights into potential anti-fibrotic mechanisms of TRPA1 activation through TGF-ß1/Smad signaling in VFFs. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

A dysphagia model with denervation of the pharyngeal constrictor muscles in guinea pigs: functional evaluation of swallowing.

Introduction: Swallowing impairment is a crucial issue that can lead to aspiration, pneumonia, and malnutrition. Animal models are useful to reveal pathophysiology and to facilitate development of new treatments for dysphagia caused by many diseases. The present study aimed to develop a new dysphagia model with reduced pharyngeal constriction during pharyngeal swallowing. Methods: We analyzed the dynamics of pharyngeal swallowing over time with the pharyngeal branches of the vagus nerve (Ph-X) bilaterally or unilaterally transected, using videofluoroscopic assessment of swallowing in guinea pigs. We also evaluated the detailed anatomy of the pharyngeal constrictor muscles after the denervation. Results: Videofluoroscopic examination of swallowing showed a significant increase in the pharyngeal area during swallowing after bilateral and unilateral sectioning of the Ph-X. The videofluoroscopy also showed significantly higher pharyngeal transit duration for bilateral and unilateral section groups. The thyropharyngeal muscle on the sectioned side was significantly thinner than that on the intact side. In contrast, the thickness of the cricopharyngeal muscles on the sectioned and intact sides were not significantly different. The mean thickness of the bilateral thyropharyngeal muscles showed a linear correlation to the pharyngeal area and pharyngeal transit duration. Discussion: Data obtained in this study suggest that denervation of the Ph-X could influence the strength of pharyngeal contraction during pharyngeal swallowing in relation to thickness of the pharyngeal constrictor muscles, resulting in a decrease in bolus speed. This experimental model may provide essential information (1) for the development of treatments for pharyngeal dysphagia and (2) on the mechanisms related to the recovery process, reinnervation, and nerve regeneration following injury and swallowing impairment possibly caused by medullary stroke, neuromuscular disease, or surgical damage from head and neck cancer.

Effects of Repeated Intracordal Glucocorticoid Injection on the Histology and Gene Expression of Rat Vocal Folds.

OBJECTIVES: Local injection of glucocorticoids (GCs) into the vocal folds has been used for treating the vocal fold lesions. While the positive effects on vocal fold nodules, polyps, or scarring have been clinically reported, some concern remains around the potential adverse effects such as vocal fold atrophy, and the mechanisms remain unclear. The present study examined the histology and gene expression of locally injected GC into the vocal folds in rats. METHODS: Thirteen-week-old male Sprague-Dawley rats were used in the experiments. Triamcinolone acetonide (TAA) or saline were administered repeatedly to the right vocal folds at a weekly interval, and rats were euthanized one week after the last administration for histological examination. Genetic examination was assessed hyaluronic acid (HA) metabolism at 1 or 3 days after a single TAA injection by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The group which underwent four TAA injections showed a significant decrease in HA in the lamina propria (LP), thickness of the LP and total cell numbers of the LP compared with the saline group. In contrast, there was no significant difference in the area of collagen accumulation and the thyroarytenoid muscle, although there was a tendency of atrophy of the muscle. After single injection of TAA, qRT-PCR showed a significant decrease in the expression of HA synthases, Has2 and Has3. CONCLUSIONS: The current animal study first demonstrates that repeated intracordal injection of GCs may lead to atrophy of vocal folds caused by decrease of deposition of HA in the LP and decrease of gene expression of Has.

Tamoxifen Alters TGF-ß1/Smad Signaling in Vocal Fold Injury.

OBJECTIVES: Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF-ß1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis. METHODS: In vitro, vocal fold fibroblasts were treated with TAM (10-8 or 10-9 M) ± TGF-ß1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real-time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre-injury day 5 to post-injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture. RESULTS: TAM (10-8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10-8 or 10-9 M) + TGF-ß1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF-ß1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment. CONCLUSIONS: TAM has antifibrotic potential via the regulation of TGF-ß1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2248-2254, 2023.

Cervical Local Cytokine Release Syndrome Following Chimeric Antigen Receptor T-cell Therapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma.

The use of chimeric antigen receptor T-cell (CAR-T) therapy for hematologic malignancies is rapidly increasing, and appropriately managing adverse events (AEs) is crucial. Cytokine release syndrome (CRS) is a common AE of CAR-T therapy, characterized by systemic symptoms such as fever and respire-circulatory failure. We present two cases with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) accompanied by a rare complication of cervical local CRS as an acute inflammatory reaction at a specific site after CAR-T infusion. Case 1: A 60-year-old gentleman with diffuse large B cell lymphoma (DLBCL) developed grade 1 CRS on day one that required three doses of tocilizumab. Then he developed remarkable cervical edema as local CRS on day five. His local CRS spontaneously improved from day seven without additional therapy. Case 2: A 70-year-old gentleman with DLBCL developed grade 1 CRS on day two that required three doses of tocilizumab. Then he developed remarkable cervical edema and muffled voice as local CRS on day three. He received dexamethasone because of concerns about airway obstruction, and his local CRS improved immediately after dexamethasone administration. Before Tisa-Cel infusion, neither patients had a lymphoma lesion in their necks. To summarize, local CRS may occur at the site without lymphoma involvement after CAR-T therapy. An appropriate diagnosis and careful observation are required to determine the need for additional treatment.

Effect of pharmacological inhibition of the pontine respiratory group on swallowing interneurons in the dorsal medulla oblongata.

OBJECTIVES: To examine the role of neurons of the pontine respiratory group (PRG) overlapping with the Kölliker-Fuse nucleus in the regulation of swallowing, we compared the activity of swallowing motor activities and interneuron discharge in the dorsal swallowing group in the medulla before and after pharmacological inhibition of the PRG. METHODS: In 23 in situ perfused brainstem preparation of rats, we recorded the activities of the vagus (VNA), hypoglossal (HNA), and phrenic nerves (PNA), and swallowing interneurons of the dorsal medulla during fictive swallowing elicited by electrical stimulation of the superior laryngeal nerve or oral water injection. Subsequently, respiratory- and swallow-related motor activities and single unit cell discharge were assessed before and after local microinjection of the GABA-receptor agonist muscimol into the area of PRG ipsilateral to the recording sites of swallowing interneurons. RESULTS: After muscimol injection, the amplitude and duration of swallow-related VNA bursts decreased to 71.3 ± 2.84 and 68.1 ± 2.76 % during electrically induced swallowing and VNA interburst intervals during repetitive swallowing decreased. Similar effects were observed for swallowing-related HNA. The swallowing motor activity was similarly qualitatively altered during physiologically induced swallowing. All 23 neurons were changed in either discharge duration or frequency after PRG inhibition, however, the general discharge patterns in relation to the motor output remained unchanged. CONCLUSION: Descending synaptic inputs from PRG provide control of the primary laryngeal sensory gate and synaptic activity of the PRG partially determine medullary cell and cranial motor nerve activities that govern the pharyngeal stage of swallowing.

Firing characteristics of swallowing interneurons in the dorsal medulla during physiologically induced swallowing in perfused brainstem preparation in rats.

Oropharyngeal swallowing is centrally mediated by a swallowing central pattern generator (Sw-CPG) in the medulla oblongata. The activity of the Sw-CPG depends on the sensory inputs determined by physical and chemical bolus properties. Here we investigate the sensory-motor integration during swallowing arising from different sensory sources. To do so we electrically stimulated the superior laryngeal nerve and we triggered swallowing with oral injections of distilled water or capsaicin solution and extracellularly recorded from swallowing interneurons in arterially perfused brainstem preparations of rats. We recorded the activities of 40 neurons, while monitoring the motor activities of the phrenic, vagal and hypoglossal nerves. Eighteen neurons responded to electrical stimulation of the ipsilateral superior laryngeal nerve, and 6 neurons were excited by oral fluid injection, while 16 non-respiratory neurons did not receive afferent inputs to either electrical or physiological stimuli. The cellular activities displayed by swallowing interneurons during electrical and physiological stimulation of pharyngeal and laryngeal afferent input reveal complex adaptations of the timing of firing patterns and frequencies. The modulation of neuronal activity is likely to contribute to the coordination of efficient bolus transfer during the pharyngeal stage of swallowing.

The Effects of Amniotic Membrane Transplantation on Vocal Fold Regeneration.

OBJECTIVES/HYPOTHESIS: Vocal fold (VF) scar and sulcus cause severe vocal problems, but optimal methods have not been established. Total replacement of the mucosa is required particularly for cases in which the whole lamina propria is occupied by severe fibrosis and vibratory function is totally lost. The amniotic membrane (AM) has been proven to have regenerative potential, as it contains stem cells and growth factors. The current study investigated the biocompatibility and effects of AM for regeneration of the VF mucosa. STUDY DESIGN: In vitro and in vivo studies. METHODS: Vocal fold fibroblasts (VFFs) from 13 Sprague-Dawley rats were seeded on AM and subjected to histology and immunohistochemistry, and gene expressions in the VFFs on AM were examined in in vitro study. Twelve New Zealand White rabbits were used in in vivo study. VFs were stripped down and were reconstructed with AM. The regenerative effects were examined 3 months later by histological examination. RESULTS: In vitro study indicated VFFs survived on AM and stained positively for Ki67, vimentin, and fibronectin. Gene expressions of Has1, Has2, and Hgf were significantly increased in the VFFs on AM compared with the other groups. The in vivo study indicated AM-transplanted VFs showed a significantly higher density of hyaluronic acid and lower density of collagen compared with sham VFs. CONCLUSIONS: The current preliminary study suggests biocompatibility and possible regenerative effects of AM for VFs. LEVEL OF EVIDENCE: NA Laryngoscope, 132:2017-2025, 2022.

Long-term clinical course of immunotactoid glomerulopathy complicated with diffuse large B-cell lymphoma.

We report a case of immunotactoid glomerulopathy (ITG) complicated with diffuse large B-cell lymphoma (DLBCL). A 68-year-old woman presented with leg edema and was diagnosed with nephrotic syndrome (NS). Renal biopsy revealed ITG. We treated the patient with prednisolone (20 mg/day) and she achieved complete remission of NS. Steroids were gradually reduced. After 1 year, the patient presented with a breast mass determined on biopsy to be DLBCL. She underwent six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Follow-up revealed complete remission of both DLBCL and ITG. NS recurred after 5 years and she was simultaneously diagnosed with recurrence of DLBCL in bone marrow. She underwent four cycles of R-EPOCH (rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin) therapy and entered remission for DLBCL. NS improved, but the treatment did not lead to remission. After 2 additional years, NS and DLBCL recurred again. She was administered rituximab and NS improved, although proteinuria tended to increase thereafter. One year later, we started prednisolone (10 mg/day), and proteinuria tended to decrease. She is currently undergoing outpatient follow-up. This case suggests that ITG with MGUS should be treated with the possibility of developing malignant hematological disease during the course.

The DNA-recognition mode shared by archaeal feast/famine-regulatory proteins revealed by the DNA-binding specificities of TvFL3, FL10, FL11 and Ss-LrpB.

The DNA-binding mode of archaeal feast/famine-regulatory proteins (FFRPs), i.e. paralogs of the Esherichia coli leucine-responsive regulatory protein (Lrp), was studied. Using the method of systematic evolution of ligands by exponential enrichment (SELEX), optimal DNA duplexes for interacting with TvFL3, FL10, FL11 and Ss-LrpB were identified as TACGA[AAT/ATT]TCGTA, GTTCGA[AAT/ATT]TCGAAC, CCGAAA[AAT/ATT]TTTCGG and TTGCAA[AAT/ATT]TTGCAA, respectively, all fitting into the form abcdeWWWedcba. Here W is A or T, and e.g. a and a are bases complementary to each other. Apparent equilibrium binding constants of the FFRPs and various DNA duplexes were determined, thereby confirming the DNA-binding specificities of the FFRPs. It is likely that these FFRPs recognize DNA in essentially the same way, since their DNA-binding specificities were all explained by the same pattern of relationship between amino-acid positions and base positions to form chemical interactions. As predicted from this relationship, when Gly36 of TvFL3 was replaced by Thr, the b base in the optimal DNA duplex changed from A to T, and, when Thr36 of FL10 was replaced by Ser, the b base changed from T to G/A. DNA-binding characteristics of other archaeal FFRPs, Ptr1, Ptr2, Ss-Lrp and LysM, are also consistent with the relationship.

Intracordal Injection of Basic Fibroblast Growth Factor in 100 Cases of Vocal Fold Atrophy and Scar.

OBJECTIVES/HYPOTHESIS: Vocal fold atrophy, scar, and sulcus reduce the vibratory function of the vocal fold mucosa, which causes severe refractory dysphonia. We have reported encouraging preliminary results using an intracordal injection of basic fibroblast growth factor (bFGF) and showed improvement in phonatory parameters and voice. The present study summarizes our experience with 100 cases of stiffened vocal folds that were treated with bFGF injections. STUDY DESIGN: Retrospective chart review with Interstitial Review Board (IRB) approval. METHODS: Local injection of bFGF was performed in 100 cases of vocal fold pathology, which included 43 cases of vocal fold atrophy, 41 cases with scar, and 16 cases with sulcus. Ten micrograms of bFGF were injected into the vocal folds under topical anesthesia 4 times in each patient. Therapeutic outcomes were examined with maximum phonation time (MPT), voice handicap index-10 (VHI-10), and GRBAS scale. RESULTS: MPT, VHI-10, and GRBAS scores significantly improved in all pathology groups. An improvement on the VHI-10 greater than five points was observed in 82% of atrophy cases, 78% of scar cases, and 67% of sulcus cases. Improvement on the VHI-10 was significantly better in the atrophy group than the scar or sulcus groups. The mild/moderate cases of scar and sulcus showed better improvement than severe cases. CONCLUSIONS: The current large case series indicates positive effects of intracordal injection of bFGF for improvement of voice with no severe adverse events. The effects appeared best for cases of atrophy, while the treatment of severe scar and sulcus requires further improvement. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2059-2064, 2021.

Anti-inflammatory and Antioxidant Effects of Japanese Herbal Medicine Kyoseihatekigan on Vocal Fold Wound Healing.

OBJECTIVES: The Japanese herbal medicine kyoseihatekigan (KHG) has been used to alleviate the symptoms of croaky voice and globus hystericus, and each of its components has anti-inflammatory and antioxidant effects. However, the mechanisms underlying these beneficial actions of KHG on the vocal folds remain largely unknown. We examined the effects of KHG on rat vocal fold wound healing and assessed its anti-inflammatory and antioxidant properties. STUDY DESIGN: Animal model. METHODS: The vocal folds of Sprague-Dawley rats were unilaterally injured under endoscopy. Rats were divided into three groups based on KHG dosing from pre injury day 4 to post injury day 3: 0 mg/kg/day (sham group), 500 mg/kg/day (1% KHG group) and 1000 mg/kg/day (2% KHG group). Histologic changes were examined to assess the degree of inflammation and oxidative stress at day 3, and fibrosis at day 56. In addition, gene expression related to pro-inflammatory cytokines and transforming growth factor-beta1 (TGF-ß1) signaling was examined by quantitative real-time polymerase chain reaction (qPCR). RESULTS: Histologic analysis showed that the 1% and 2% KHG treatments significantly decreased cell infiltration and the 4-hydroxy-2-nonenalx-immunopositive area, and increased hyaluronic acid at day 3. Both KHG treatments significantly decreased fibrosis at day 56. qPCR revealed that mRNA of interleukin-1ß and cyclooxygenase-2 were significantly suppressed at day 1 and TGF-ß1 mRNA was significantly downregulated at day 5 in both KHG groups. CONCLUSIONS: The current findings suggest that KHG has anti-inflammatory and antioxidant effects in the early phase of vocal fold wound healing, which can lead to better wound healing with less scar formation.

Influences of GABAergic Inhibition in the Dorsal Medulla on Contralateral Swallowing Neurons in Rats.

OBJECTIVES: We aimed to examine the effect of unilateral inhibition of the medullary dorsal swallowing networks on the activities of swallowing-related cranial motor nerves and swallowing interneurons. METHODS: In 25 juvenile rats, we recorded bilateral vagal nerve activity (VNA) as well as unilateral phrenic and hypoglossal activity (HNA) during fictive swallowing elicited by electrical stimulation of the superior laryngeal nerve during control and following microinjection of the GABA agonist muscimol into the caudal dorsal medulla oblongata in a perfused brainstem preparation. In 20 animals, swallowing interneurons contralateral to the muscimol injection side were simultaneously recorded extracellularly and their firing rates were analyzed during swallowing. RESULTS: Integrated VNA and HNA to the injection side decreased to 49.0 ± 16.6% and 32.3 ± 17.9%, respectively. However, the VNA on the uninjected side showed little change after muscimol injection. Following local inhibition, 11 out of 20 contralateral swallowing interneurons showed either increased or decreased of their respective firing discharge during evoked-swallowing, while no significant changes in activity were observed in the remaining nine neurons. CONCLUSION: The neuronal networks underlying the swallowing pattern generation in the dorsal medulla mediate the ipsilateral motor outputs and modulate the contralateral activity of swallowing interneurons, suggesting that the bilateral coordination of the swallowing central pattern generator regulates the spatiotemporal organization of pharyngeal swallowing movements. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2187-2198, 2021.

Relationship between number of menopausal symptoms and work performance in Japanese working women.

OBJECTIVE: The presence of various menopausal symptoms could decrease work performance because symptom management strategies differ, and it is difficult to control all symptoms at work. The aim of this study was to examine the relationship between the number of menopausal symptoms experienced and work performance in working women. METHODS: An online cross-sectional study was conducted with 599 working Japanese women aged 45 to 65 years. To represent work performance, absolute presenteeism was measured using the Japanese version of the World Health Organization and Work Performance Questionnaire short form, and menopausal symptoms were measured using the Greene Climacteric Scale. The total number of subscales on which a participant scored more than one point represented the number of menopausal symptoms. RESULTS: Participants' mean age was 54.2 years, and 60.6% were postmenopausal. Their mean Greene Climacteric Scale score and mean absolute presenteeism score were 10.5 ± 10.6 and 61.7 ±â€Š17.9, respectively. The proportions of participants who provided care for a family member, who had chronic disease, and who undertook regular exercise were significantly different among the four groups. After adjusting for other factors, absolute presenteeism was negatively correlated with the number of menopausal symptoms experienced (ß = -0.13, P < 0.001). CONCLUSIONS: Higher numbers of menopausal symptoms were correlated with lower work performance. The maintenance of health and the provision of appropriate working environments would help working women and improve work performance by reducing menopausal symptoms.

Laryngeal afferent modulation of swallowing interneurons in the dorsal medulla in perfused rats.

OBJECTIVES: The purpose of this study was to investigate the influence of laryngeal afferent inputs on brainstem circuits that mediate and transmit swallowing activity to the orofacial musculature. METHODS: Experiments were performed on 19 arterially perfused juvenile rats. The activities of swallowing interneurons in relation to their respective motor outputs in the hypoglossal and vagus nerves were assessed during fictive swallowing with or without concurrent laryngeal sensory stimulation at intensities of 20, 40, and 60 µA. RESULTS: The hypoglossal nerve activity was gradually enhanced with increasing intensity of the sensory stimulation, while the vagus nerve activity was not altered. The activities of various interneurons were modulated by the laryngeal stimulation, but more than 50% of the recorded neurons were inhibited by the stimulation. Some interneurons demonstrated no obvious change in their discharge rates with laryngeal sensory stimulation during fictive swallowing. CONCLUSION: Laryngeal afferent inputs partially modulated the swallowing motor activity via enhanced or suppressed activities of the swallowing interneurons, while the essential motor pattern underlying the pharyngeal stage of swallowing remained basically unchanged. Thus, the output patterns of the complex sequential movements of swallowing could be basically predetermined and further adjusted according to sensory information related to the properties of the ingested food by a swallowing central pattern generator. LEVEL OF EVIDENCE: NA Laryngoscope, 130: 1885-1893, 2020.

Activity of swallowing-related neurons in the medulla in the perfused brainstem preparation in rats.

OBJECTIVES/HYPOTHESIS: We aimed to investigate and validate the cellular activity patterns and the potential topographical organization of neurons of the medullary swallowing pattern generator (Sw-CPG). We used the perfused brainstem preparation as an innovative experimental model that allows for stable neuronal recording in the brainstem. STUDY DESIGN: Animal model. METHODS: Experiments were conducted in 14 juvenile Wistar rats. The activities of the phrenic, vagus, and hypoglossal nerves were recorded at baseline, and fictive swallowing was elicited by stimulation of the superior laryngeal nerve. Extracellular action potentials of 72 swallowing-related neurons were recorded in the Sw-CPG of the dorsal medulla oblongata. RESULTS: Neurons could be classified into three types: sensory relay, and neurons that were excited or inhibited during fictive swallowing. Approximately one-third of the neurons likely received monosynaptic input from the laryngeal afferents. One-third of neurons recorded showed respiratory-related activity, most of which exhibited inspiratory modulation. The neurons were widely distributed in the nucleus tractus solitarius and reticular formation. CONCLUSIONS: The perfused brainstem preparation of rat fully preserves the Sw-CPG. The recorded cellular activities and general topographical organization of swallowing neurons are in accordance with previous in vivo studies. Thus, the perfused brainstem preparation is an ideal experimental model to advance the understanding of neuronal mechanisms underlying swallowing. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E72-E79, 2019.

An autopsy case of TAFRO syndrome with membranoproliferative glomerulonephritis-like lesions.

TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) is an atypical manifestation of multicentric Castleman's disease. Although overproduction of interleukin-6, vascular endothelial growth factor, and other cytokines may partially explain the pathophysiology of this rare syndrome, the precise mechanisms underlying the renal dysfunction associated with the condition remain unclear. Here, we describe a case of a 69-year-old male with TAFRO syndrome. He was treated with immunosuppressive agents and his renal function improved. Tapering of immunosuppressive agents resulted in a deterioration of renal function and an elevation of C-reactive protein. After 20 months of treatment, the patient died from tuberculous peritonitis and gastrointestinal bleeding. An autopsy revealed miliary tuberculosis, mediastinal lymphadenopathy, and gastric ulcers. Renal histopathology showed a membranoproliferative glomerulonephritis-like appearance. Almost all glomeruli showed lobular formations with mesangial proliferation and duplication of glomerular capillary walls on light microscopy. Immunofluorescence showed deposition of C1q and IgM along the glomerular capillary walls. Electron microscopy showed mesangial expansion and widening of the subendothelial space with a large number of electron-dense deposits. The glomerular lesions might be characteristic of TAFRO syndrome, and were regarded as the main cause of the patient's renal dysfunction.