Occult endocrine disorders newly diagnosed in patients with post-COVID-19 symptoms.

Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.

Carotid Endarterectomy With Shunt-A Stepwise Surgical Technique Demonstration for Trainees: 2-Dimensional Operative Video.

Carotid endarterectomy (CEA) is a common cerebrovascular surgery and is an effective treatment option for patients with carotid stenosis.1-4 Although the routine or selective use of a shunt is still debatable,5 the CEA technique is generally well-established. We believe that bloodless and "shallow and wide" operative fields make CEA safe and successful. Maintaining a bloodless operative field is highly crucial to prevent postoperative cervical hematoma and damage to anatomic structures, such as the hypoglossal and vagus nerves, because it facilitates their identification. In the cases of CEA, antiplatelet medications are usually continued, and systemic heparinization is performed intraoperatively; therefore, further meticulous hemostasis should be performed than in other neurological surgery cases. The 2-step pull-up technique, which involves pulling up loose connective tissue surrounding the carotid arteries in addition to the carotid sheath, makes the operative field "shallow and wide." This technique allows the internal carotid artery to move from deep to superficial, making CEA feasible, particularly when placing a shunt. This video illustrates the CEA technique used for symptomatic mild carotid stenosis in a 66-year-old man with vulnerable plaques. Evolving carotid artery stenting should facilitate the improvement of the operative technique to increase the safety and accordingly train young surgeons. This video is intended to increase familiarity with CEA because carotid artery stenting decreases CEA indications for carotid stenosis and diminishes proficiency in managing CEA. The patient consented to the publication of his image. Patient consent was obtained to perform the surgery and publish the surgical video.

Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic.

PURPOSE: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated. METHODS: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances. RESULTS: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints. CONCLUSION: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.

Characteristics of Persistent Symptoms Manifested after SARS-CoV-2 Vaccination: An Observational Retrospective Study in a Specialized Clinic for Vaccination-Related Adverse Events.

Background: Although many adverse reactions after SARS-CoV-2 vaccination have been reported, there have been few comprehensive studies on persistent symptoms after SARS-CoV-2 vaccination. The aim of this study was to determine the clinical characteristics of patients with various persistent symptoms after SARS-CoV-2 vaccination. Methods: A retrospective descriptive study was performed for patients who visited a specialized clinic established at Okayama University Hospital to evaluate adverse events after SARS-CoV-2 vaccination during the period from April 2021 to March 2023. Results: Descriptive analysis was performed for 121 of 127 patients who visited the clinic during the study period, and separate analysis was performed for the other 6 patients who had serious complications, who required treatment with prednisolone, and who had persistent symptoms. The median [interquartile range] age of the patients was 48 years [31-64 years], and the patients included 44 males (36.4%) and 77 females (63.6%). The most frequent symptoms were sensory impairment (34 patients, 28.1%), general fatigue (30 patients, 24.8%), fever/low-grade fever (21 patients, 17.4%), and headache (21 patients, 17.4%). Serious complications included myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sarcoidosis, aseptic meningitis, neuromyelitis optica spectrum disorders (NMOSDs), tendon adhesions, and idiopathic thrombocytopenia. Conclusions: Although causal relationships were not determined, 15 persistent symptoms after SARS-CoV-2 vaccination were characterized. All of the symptoms had onset from 12 hours to one week after vaccination, with 10 symptoms persisting for 6 months or longer. The most frequent symptom was sensory impairment.

Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID.

OBJECTIVE: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. METHODS: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated. RESULTS: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients' backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 µg/L, interquartile range (IQR): 58.8-353.8) than in the non-ME/CFS group (98.2 µg/L, 40.4-251.5) and no-fatigue group (86.7 µg/L, 37.5-209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05). CONCLUSIONS: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients.

Improving taxonomic classification of marine zooplankton by molecular approach: registration of taxonomically verified 18S and 28S rRNA gene sequences.

Background: Zooplankton plays an important role in the marine ecosystem. A high level of taxonomic expertise is necessary for accurate species identification based on morphological characteristics. As an alternative method to morphological classification, we focused on a molecular approach using 18S and 28S ribosomal RNA (rRNA) gene sequences. This study investigates how the accuracy of species identification by metabarcoding improves when taxonomically verified sequences of dominant zooplankton species are added to the public database. The improvement was tested by using natural zooplankton samples. Methods: rRNA gene sequences were obtained from dominant zooplankton species from six sea areas around Japan and registered in the public database for improving the accuracy of taxonomic classifications. Two reference databases with and without newly registered sequences were created. Comparison of detected OTUs associated with single species between the two references was done using field-collected zooplankton samples from the Sea of Okhotsk for metabarcoding analysis to verify whether or not the newly registered sequences improved the accuracy of taxonomic classifications. Results: A total of 166 sequences in 96 species based on the 18S marker and 165 sequences in 95 species based on the 28S marker belonging to Arthropoda (mostly Copepoda) and Chaetognatha were registered in the public database. The newly registered sequences were mainly composed of small non-calanoid copepods, such as species belonging to Oithona and Oncaea. Based on the metabarcoding analysis of field samples, a total of 18 out of 92 OTUs were identified at the species level based on newly registered sequences in the data obtained by the 18S marker. Based on the 28S marker, 42 out of 89 OTUs were classified at the species level based on taxonomically verified sequences. Thanks to the newly registered sequences, the number of OTUs associated with a single species based on the 18S marker increased by 16% in total and by 10% per sample. Based on the 28S marker, the number of OTUs associated with a single species increased by 39% in total and by 15% per sample. The improved accuracy of species identification was confirmed by comparing different sequences obtained from the same species. The newly registered sequences had higher similarity values (mean >0.003) than the pre-existing sequences based on both rRNA genes. These OTUs were identified at the species level based on sequences not only present in the Sea of Okhotsk but also in other areas. Discussion: The results of the registration of new taxonomically verified sequences and the subsequent comparison of databases based on metabarcoding data of natural zooplankton samples clearly showed an increase in accuracy in species identification. Continuous registration of sequence data covering various environmental conditions is necessary for further improvement of metabarcoding analysis of zooplankton for monitoring marine ecosystems.

Stimulatory effects of vasopressin on progesterone production and BMP signaling by ovarian granulosa cells.

The aim of the present study was to clarify the effects of arginine vasopressin (AVP) on ovarian steroid production and its functional relationship to the ovarian bone morphogenetic protein (BMP) system. The results showed that AVP treatment significantly increased gonadotropin- and forskolin-induced progesterone synthesis by primary culture of rat granulosa cells and human granulosa cells, respectively. In contrast, estradiol production was not significantly affected by AVP. Treatment with AVP significantly increased forskolin-induced cAMP synthesis by human granulosa cells and mRNA levels of the progesterogenic enzymes CYP11A1 and HSD3B2 in the cells. On the other hand, AVP also enhanced BMP-15-induced phosphorylation of SMAD1/5/9 and ID1 transcription. It was further revealed that the expression levels of BMP receptors, including ALK3, ALK6 and BMPR2, were upregulated by AVP. Collectively, the results indicate that AVP stimulates progesterone production via the cAMP-PKA pathway with upregulation of BMP signaling that inhibits progesterone production, which may lead to fine adjustment of progesterone biosynthesis by granulosa cells.

Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients.

OBJECTIVES: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients. METHODS: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 µg/dL (10.7 µmol/L) were compared with characteristics of patients with normozincemia. RESULTS: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = -0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 µg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue. CONCLUSIONS: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients.

Trends in Long COVID Symptoms in Japanese Teenage Patients.

Background: Since the start of the global pandemic of coronavirus disease 2019 (COVID-19), not only adults but also many children have suffered from it. However, the clinical characteristics of long COVID in children remain unclear. Methods: In this retrospective observational study conducted in a single facility, we reviewed the medical records of all long COVID patients who visited Okayama University Hospital from February 2021 to October 2022, and we compared the clinical characteristics of long COVID in teenagers (11 to 18 years of age) with those in adults. Results: Data for 452 long COVID patients including 54 teenagers (11.9%) were analyzed. Fatigue was the most frequent symptom in teenagers (55.6% of the patients) and also in adults. On the other hand, the percentage of teenagers who complained of headache, which was the second most frequent complaint, was significantly higher than the percentage of adults (35.2% vs. 21.9%, p < 0.05). A comparison of the frequencies of symptoms depending on the viral variant showed that fatigue and headache were predominant symptoms in the Omicron variant phase. Of the 50 teenagers who were enrolled in schools, 28 (56.0%) could not attend school due to long COVID symptoms. The most common symptoms as reasons for absence from school were fatigue (85.7% of the patients), headache (42.9%), and insomnia (32.1%). Conclusions: Attention should be paid to the symptoms of fatigue and headache in teenagers with long COVID.

Midline Suboccipital Unilateral Trans-Cerebellomedullary Fissure Approach for Clipping of Ruptured VA-PICA Aneurysm: Two-Dimensional Operative Video.

The vertebral artery-posterior inferior cerebellar artery (VA-PICA) aneurysm poses a technical challenge for microsurgical clipping due to its anatomical complexity, which requires dissection of lower cranial nerves. Endovascular treatment is regarded as a feasible first-line therapeutic option for VA-PICA aneurysm because it has an acceptable aneurysm occlusion rate and is less invasive. However, microsurgical clipping remains an effective treatment option. We present the case of a 62-year-old man who presented with subarachnoid hemorrhage (SAH) due to a ruptured VA-PICA aneurysm. Neuroradiologic examination revealed a 2-3 mm medially pointing left VA-PICA aneurysm with acute obstructive hydrocephalus due to massive SAH in the posterior cranial fossa. As the patient had acute obstructive hydrocephalus and a relatively small aneurysm, we selected clipping over endovascular treatment. Because the aneurysm was located close to the midline and anterolateral to the medulla oblongata, we approached it from the midline. A midline suboccipital craniotomy, C1 laminectomy, and drilling of the left condylar fossa were performed; a unilateral cerebellomedullary fissure opening was added; and the aneurysm was clipped. Postoperative neuroradiologic examinations revealed complete obliteration of the aneurysm. As shown in this video, unilateral cerebellomedullary fissure opening combined with adequate removal of the condylar fossa provides a wide operative field in the cerebellomedullary cistern while avoiding strong retraction of the cerebellum. We believe that this technique makes VA-PICA aneurysm clipping safe and successful. Patient consent was obtained to perform the surgery and to publish the surgical video (Video 1).

Oxytocin enhances progesterone production with upregulation of BMP-15 activity by granulosa cells.

To elucidate the reproductive role of oxytocin (OXT) in ovarian steroidogenesis and its functional interaction with bone morphogenetic proteins (BMPs), the effects of OXT on ovarian steroidogenesis were investigated by utilizing primary culture of rat granulosa cells and human granulosa KGN cells. Here we revealed that the OXT receptor was expressed in both rat and human granulosa cells and that OXT treatment significantly increased follicle-stimulating hormone (FSH)- and forskolin (FSK)-induced progesterone production, but not estradiol production, by rat and human granulosa cells, respectively. In accordance with the effects of OXT on progesterone production, OXT enhanced mRNA expression of CYP11A1 and HSD3B2 induced by FSK in human granulosa cells. Of note, OXT enhanced the phosphorylation of SMAD1/5/9 and the transcription of ID1 induced by BMP-15, but not those induced by BMP-6, in human granulosa cells. It was also revealed that OXT treatment upregulated the expression of BMPR2, a crucial type-II receptor of BMP-15, and enhanced the BMP-15-induced expression of inhibitory SMAD6 by human granulosa cells. Collectively, it was shown that OXT accelerates ovarian progesterone synthesis with upregulation of BMP-15 activity, leading to a fine-tuning of ovarian steroidogenesis (186 words).

Characteristics of Sleep Disturbance in Patients with Long COVID: A Retrospective Observational Study in Japan.

OBJECTIVES: The objective of this study was to determine the clinical and endocrinological features of sleep disturbance in patients with long COVID. METHODS: This study was a single-center retrospective observational study for patients who visited the COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital in Japan during the period from 15 February 2021 to 29 July 2022. The long COVID patients were divided into two groups based on the presence or absence of sleep disturbance, and the clinical and laboratory characteristics of the patients were analyzed. RESULTS: Out of 363 patients with long COVID, after excluding 6 patients, 60 patients (16.5%) (55% males, median age of 38 years) complaining of sleep disturbance were compared with 303 patients (83.5%) (43% males, median age of 40 years) without sleep-related symptoms. Although there were no significant differences in clinical backgrounds and severities of COVID-19 between the two groups by the multivariate analysis, the percentage of long COVID patients with sleep disturbance was significantly increased among patients infected in the Omicron-dominant phase. In addition, the prevalence rate of sleep disturbance in patients when infected in the Omicron phase (24.8%) was two-times higher than that in patients infected in the Delta phase (12.8%). Of note, the percentages of patients with sleep disturbance who also complained of general fatigue, headache, concentration loss, anxiety, low-grade fever, and brain fog symptoms were higher than the percentages of patients without sleep disturbance who had the same complaints. Among the types of sleep disturbance, the percentage of patients who complained of loss of sleep induction (75%) was much higher than the percentage of patients with early-awakening sleep disturbance (6.7%), and many of the patients with mid-awakening types of insomnia had brain fog symptoms. Endocrine examinations revealed that long COVID patients with sleep disturbance had significantly higher levels of plasma adrenocorticotropin and lower levels of serum growth hormone, suggesting the presence of hypothalamic-pituitary stress. CONCLUSION: The prevalence of sleep disturbance has been increasing in long COVID patients infected in the Omicron phase with a certain clinical and endocrine trend.

Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing.

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

Transitional Changes in Fatigue-Related Symptoms Due to Long COVID: A Single-Center Retrospective Observational Study in Japan.

Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p < 0.01), dysgeusia (14% vs. 40%, ** p < 0.01) and hair loss (7% vs. 28%, ** p < 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p < 0.05), insomnia (26% vs. 13%, * p < 0.05) and cough (20% vs. 7%, ** p < 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized.

Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID.

Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.

Application of Kampo Medicines for Treatment of General Fatigue Due to Long COVID.

Evidence regarding treatment for the acute phase of COVID-19 has been accumulating, but specific treatment for long COVID/post-COVID-19 condition has not yet been established. Treatment with herbal medicine might be one treatment option for long COVID, but there has been little research on the effectiveness of herbal medicine for long COVID. The aim of this study was to clarify the prescription patterns of Kampo medicines, which are herbal medicines that originated in China and were developed in Japan, for the treatment of general fatigue due to long COVID. A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period from Feb 2021 to Dec 2021 with a focus on symptoms accompanying general fatigue and prescriptions of Kampo medicine. Among the clinical data obtained from medical records of 195 patients, clinical data for 102 patients with general fatigue and accompanying symptoms were analyzed. The patients had various symptoms, and the most frequent symptoms accompanying general fatigue were dysosmia, dysgeusia, headache, insomnia, dyspnea, and hair loss. Prescriptions of Kampo medicine accounted for 24.1% of the total prescriptions (n = 609). The most frequently prescribed Kampo medicine was hochuekkito (71.6%) and other prescribed Kampo medicines were tokishakuyakusan, ryokeijutsukanto, juzentaihoto, hangekobokuto, kakkonto, ninjin'yoeito, goreisan, rikkunshito, and keishibukuryogan. Since the pathophysiology of general fatigue after an infectious disease is, in general, considered a qi deficiency in Kampo medicine, treatments with such compensation agents can be the major prescription as a complement for the qi. In conclusion, Kampo medicine can be one of the main pharmacological treatments for long COVID accompanying general fatigue.

Hormonal trends in patients suffering from long COVID symptoms.

Symptoms of long COVID are complex and long-lasting, and endocrine dysfunction might be involved in the underlying mechanisms. In this study, to clarify the hormonal characteristics of long COVID patients, laboratory data for patients who visited the outpatient clinic for long COVID were evaluated. A retrospective analysis was performed for patients who visited Okayama University Hospital during the period from Feb 2021 to Dec 2021 with focus on the interrelationships between major symptoms and endocrine data. Information and laboratory data were obtained from medical records for 186 patients. The patients had various symptoms, and the most frequent symptoms were general malaise, dysosmia/dysgeusia, hair loss, headache, dyspnea, and sleeplessness. Patients who were suffering from fatigue and dysosmia/dysgeusia were younger, while hair loss was more frequent in older and female patients. As for the characteristics of patients suffering from general fatigue, the scores of depression and fatigue were positively correlated with serum levels of cortisol and free thyroxin (FT4), respectively. Also, patients suffering from general fatigue had lower levels of serum growth hormone and higher levels of serum FT4, while patients with dysosmia/dysgeusia had a significantly lower level of serum cortisol. Serum thyrotropin (TSH) levels were higher and the ratios of FT4/TSH were lower in the initially severe cases, suggesting occult hypothyroidism. In addition, the ratios of plasma adrenocorticotropin to serum cortisol were decreased in patients with relatively high titers of serum SARS-CoV-2 antibody. Thus, hormonal changes seem to be, at least in part, involved in the persistent symptoms of long COVID.

Inflammation of the adipose tissue in the retroperitoneal cavity adjacent to pelvic endometriosis.

AIM: Peritoneal endometriosis is a chronic inflammatory disease particularly associated with macrophages. Of note, adipose tissues with fibrotic changes in the context of peritoneal endometriotic lesions are often observed during surgery. However, the characteristics of fibrotic adipose tissues in endometriosis are still unknown. In this study, we investigated the inflammatory status of retroperitoneal adipose tissues adjacent to pelvic endometriotic lesions. METHODS: Thirty-two patients who underwent surgical treatment were assigned to either the endometriosis (n = 16) or the control (n = 16) groups. Retroperitoneal adipose tissues around the uterus were collected from patients in both groups. Fibrosis was evaluated via Masson's trichrome staining. Macrophage infiltration, the expression of fatty acid-binding protein 4 (FABP4), and angiogenesis in the retroperitoneal adipose tissues were evaluated via immunohistochemistry. The mRNA expression levels of cytokines was also evaluated in the adipose tissues using real-time PCR. RESULTS: There was more fibrosis and angiogenesis in the adipose tissues adjacent to the endometriotic lesions with a significantly higher level of infiltration of macrophages and a predominance of the M1 type in the endometriosis group compared to the control group. In addition, FABP4 positivity in the adipose tissues of the peritoneum was significantly higher in the endometriosis group versus the control group. Moreover, the mRNA expression levels of FABP4, VEGF, and proinflammatory cytokines were also significantly higher in the endometriosis group. CONCLUSION: Altogether, our results showed that the adipose tissue adjacent to endometriotic lesions are inflamed with fibrosis and angiogenesis.

Synthesis of a chiral metallo-capsule composed of concave molecules and chirogenesis upon fullerene binding.

An enantiopure molecular capsule was synthesized quantitatively using complexation of four phosphangulenes as concave molecules with four Zn2+ ions and applied to fullerene binding and chirogenesis. The capsule encapsulated selectively fullerene and its derivatives based on the size of cavity. The fullerene C60 incorporated in the capsule exhibited induced-CD signals at the transitions of C60.

Involvement of BMP-15 in glucocorticoid actions on ovarian steroidogenesis by rat granulosa cells.

To elucidate the impact of glucocorticoids on ovarian steroidogenesis and its molecular mechanism by focusing on bone morphogenetic proteins (BMPs), we examined the effect of dexamethasone (Dex) on estradiol and progesterone synthesis by using primary culture of rat granulosa cells. It was revealed that Dex treatment dose-dependently decreased estradiol production but increased progesterone production induced by follicle-stimulating hormone (FSH) by granulosa cells. In accordance with the effects of Dex on estradiol synthesis, Dex suppressed P450arom mRNA expression and cAMP synthesis induced by FSH. Dex treatment in turn enhanced basal as well as FSH-induced levels of mRNAs encoding the enzymes for progesterone synthesis including P450scc and 3ßHSD but not StAR and 20αHSD. Of note, Dex treatment significantly upregulated transcription of the BMP target gene Id-1 and Smad1/5/9 phosphorylation in the presence of BMP-15 among the key ovarian BMP ligands. It was also found that Dex treatment increased the expression level of BMP type-I receptor ALK-6 among the type-I and -II receptors for BMP-15. Inhibitory Smad6/7 expression was not affected by Dex treatment. On the other hand, BMP-15 treatment upregulated glucocorticoid receptor (GR) expression in granulosa cells. Collectively, it was revealed that glucocorticoids elicit differential effects on ovarian steroidogenesis, in which GR and BMP-15 actions are mutually enhanced in granulosa cells.