[A Case Report of Metastatic Breast Cancer with Peritoneal Metastasis and Massive Ascites Responding to CDK4/6 Inhibitor(Palbociclib)].

A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy. Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.

Micromapping testicular sperm extraction: A new technique for microscopic testicular sperm extraction in nonobstructive azoospermia.

Purpose: In microscopic testicular sperm extraction (mTESE) for nonobstructive azoospermia (NOA), sperm can be recovered relatively easily in some cases, and mTESE may be retrospectively considered excessive. However, mTESE is routinely performed in the majority of NOA patients because of the difficulty in predicting tissue status. A minimally invasive and comprehensive sperm retrieval method that allows on-the-spot tissue assessment is needed. We have developed and evaluated a novel sperm retrieval technique for NOA called micromapping testicular sperm extraction (MMTSE). Methods: MMTSE involves dividing the testis into four sections and making multiple small needle holes in the tunica albuginea to extract seminiferous tubules and retrieve sperm. The sperm-positive group by MMTSE (Group I) underwent additional tissue collection (ATC) via a small incision, whereas the sperm-negative group by MMTSE (Group 0) underwent mTESE. Results: In total, 40 NOA participants underwent MMTSE. Group I included 15 patients and Group 0 included 25 patients. In Group 1, sperm were recovered from all patients by ATC. In Group 0, sperm were recovered in 4 of 25 cases using mTESE. Conclusions: MMTSE shows promise as a simple method that comprehensively searches testicular tissue and retrieves sperm using an appropriate method while minimizing patient burden.

[18F]FES PET Resolves the Diagnostic Dilemma of COVID-19-Vaccine-Associated Hypermetabolic Lymphadenopathy in ER-Positive Breast Cancer.

Coronavirus disease (COVID-19) vaccination is known to cause a diagnostic dilemma due to false-positive findings on [18F]FDG PET in vaccine-associated hypermetabolic lymphadenopathy. We present two case reports of women with estrogen-receptor (ER)-positive cancer of the breast who were vaccinated for COVID-19 in the deltoid muscle. [18F]FDG positron emission tomography (PET) demonstrated primary breast cancer and multiple axillary lymph nodes with increased [18F]FDG uptake, diagnosed as vaccine-associated [18F]FDG-avid lymph nodes. Subsequent [18F]FES PET revealed single axillary lymph node metastasis in the vaccine-associated [18F]FDG-avid lymph nodes. To the best of our knowledge, this is the first study showing the usefulness of [18F]FES PET in diagnosing axillary lymph node metastasis in COVID-19-vaccinated patients harboring ER-positive breast cancer. Thus, [18F]FES PET has potential applications in the detection of true-positive metastatic lymph nodes in patients with ER-positive breast cancer regardless of the ipsilateral or contralateral side, who have received COVID-19 vaccination.

Synthesis of amphiphilic chiral salen complexes and their conformational manipulation at the air-water interface.

A series of amphiphilic salen complexes, [L1a,bM] and [L2a,bM], were designed and synthesized. These complexes consist of two or four hydrophilic triethylene glycol (TEG) chains and a hydrophobic π-extended metallosalen core based on naphthalene or phenanthrene. The obtained amphiphilic complexes, [L1bM] (M = Ni, Cu, Zn), formed a monolayer at the air-water interface, while the monocationic [L1bCo(MeNH2)2](OTf) did not form a well-defined monolayer. The number of hydrophilic TEG chains also had an influence on the monolayerformation behavior; the tetra-TEG derivatives, [L1bNi] and [L2bNi], showed a pressure rise at a less compressed region than the bis-TEG derivatives, [L1aNi] and [L2aNi]. In addition, the investigation of their compressibility and compression modulus suggested that the tetra-TEG derivatives, [L1bNi] and [L2bNi], are more flexible than the corresponding bis-TEG analogues, [L1aNi] and [L2aNi], and that the phenanthrene derivatives [L1a,bNi] were more rigid than the corresponding naphthalene analogues, [L2a,bNi]. The Langmuir-Blodgett (LB) films of one of the complexes, [L1bNi], showed CD spectra slightly different from that in solution, which may originate from the unique anisotropic environment of the air-water interface. Thus, we demonstrated the possibility of controlling the chiroptical properties of metal complexes by mechanical compression.

FLAMES with Elevated Myelin Basic Protein Followed by Myelitis.

The pathophysiology of unilateral cortical fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) is unclear. A 26-year-old man was referred because of a seizure. FLAIR showed an increased signal intensity and swelling of the right frontal cortex. His symptoms and imaging abnormalities were improved after intravenous methylprednisolone therapy. MOG antibody was detected both in serum and cerebrospinal fluid (CSF). Therefore, the patient was diagnosed with FLAMES. Myelin basic protein (MBP) was elevated in CSF. The high MBP value in the CSF in the present case suggested that demyelination as well as inflammation can occur in some FLAMES patients.

Metastatic invasive lobular breast cancer presenting as linitis plastica of the colon: Tumour characterization using [18 F]FES PET/MRI.

Metastatic invasive lobular breast cancer (ILC) to the colon is rare and usually ER-positive. We present an ER-negative case of metastatic ILC presenting as linitis plastica of the colon where [18 F]FES PET/MRI allowed the evaluation of the ER phenotypic transformation in the colonic metastasis from the ER-positive breast ILC in vivo.

18F-Fluoroestradiol Tumor Uptake Is Influenced by Structural Components in Breast Cancer.

PURPOSE: Estrogen receptor (ER) is expressed in the majority of invasive breast cancer and is an important prognostic indicator. The tumor stroma also plays an important role in disease progression. This study evaluated the effect of stromal components on 16α-[18F]-fluoro-17ß-estradiol (18F-FES) uptake in breast cancer and proposed a partial-volume correction method for 18F-FES PET based on histopathological analyses. PATIENTS AND METHODS: Fifteen patients with biopsy-confirmed breast cancer underwent preoperative 18F-FES PET. Estrogen receptor expression in biopsy specimens was assayed by immunohistochemistry, cellular components in surgical specimens were measured using hematoxylin-eosin staining, and nuclear components in surgical and biopsy specimens were measured using Azan-Mallory staining. The relationship between 18F-FES SUV of the primary tumor and histopathological findings including ER expression, the Allred score, ER-positive cellular component ratio, and ER-positive nuclear component ratio (NCR) was examined. The relationship between stroma-free 18F-FES SUV and ER expression was also examined. RESULTS: 18F-FES uptake was not significantly positively correlated with ER expression (r = 0.44, P = 0.10). 18F-FES uptake was significantly correlated with the Allred score, ER-positive cellular component ratio, and ER-positive NCR in surgical specimens (ρ = 0.60, P = 0.02; r = 0.55, P = 0.03; and r = 0.65, P = 0.01, respectively). 18F-FES uptake was predominantly correlated with ER-positive NCR in biopsy specimens (r = 0.84, P < 0.001). Stroma-free 18F-FES SUV was significantly correlated with ER expression (r = 0.78, P < 0.01). CONCLUSIONS: 18F-FES PET predominantly demonstrates the level of ER expression in breast cancer cell nucleus. Although tumor 18F-FES uptake is affected by the degree of stromal components, the partial volume effect on the uptake can be corrected by stroma-volume fraction in Azan-Mallory staining.

Six-year follow-up of children born from vitrified oocytes.

RESEARCH QUESTION: Are children born from vitrified-warmed oocytes physically or mentally different from naturally conceived children? DESIGN: Intracytoplasmic sperm injection (ICSI) of vitrified-warmed oocytes was performed for 282 patients (307 cycles) from August 2000 to March 2020. Long-term follow-up of children born from vitrified-warmed oocytes was performed via a questionnaire that was sent to the parents at regular intervals from 3 to 72 months after the child's birth. Questionnaires were sent 11 times from birth to the age of 6 years. The development of motor function and mental status was evaluated as the primary outcome, based on the reported data. Subsequently, patients were divided into four groups by age at oocyte retrieval (20-29, 30-34, 35-39, and 40 years or older). Clinical outcomes were calculated as a secondary outcome. RESULTS: For the 282 patients, the birth of 116 babies was reported (110 singletons and three sets of twins), and seven cases are, at the time of writing, unconfirmed. The results of the survey found physical parameters in singletons to be equivalent to the nationally reported average data issued by the Ministry of Health, Labor and Welfare of Japan. CONCLUSION: This is the first follow-up report of children born from vitrified-warmed oocytes followed by ICSI. The data suggested that the responses from the study participants on the mental and physical development of children were comparable to the data reported by the government, although more responses from patients should be collected to allow further study.

Cholesterol Crystal in Thrombus Removed by Mechanical Thrombectomy Should be a Strong Marker for Aortogenic Embolic Stroke.

Aortogenic embolic stroke (AES) is an important stroke mechanism. However, as many stroke patients have aortic atheromatous lesions, it is unclear whether these lesions are the cause of these strokes. Cholesterol crystals are the solid, crystalline form of cholesterol that is found in atherosclerosis, but not in cardiac diseases such as atrial fibrillation, valvular diseases, and cardiomyopathy. Therefore, if a cholesterol crystal is found in a thrombus removed by mechanical thrombectomy (MT), this makes it possible to diagnose a patient as having an atheromatous lesion. Here, we report an AES case with a cholesterol crystal found in a thrombus removed by MT. A 67-year-old man was admitted due to consciousness disturbance, aphasia, and right hemiplegia. Diffusion-weighted imaging (DWI) showed a hyperintense area in the left frontal lobe, and magnetic resonance angiography demonstrated a branch occlusion of the left middle cerebral artery (MCA). MT was performed 1.5 h after stroke onset, with the thrombus removed and a left occluded MCA completely recanalized. Carotid duplex ultrasonography did not reveal any plaque in the carotid artery. Echocardiography did not show any abnormal function or findings, including thrombus. Transesophageal echocardiography showed a 4.9 mm atheromatous lesion at the aortic arch. Therefore, we suspected this patient as having an AES due to the embolic source of atheromatous lesion at the aortic arch. Pathological examination of the embolus revealed a cholesterol crystal cleft in the thrombus. Therefore, we diagnosed this patient as having AES caused by an atheromatous lesion at the aortic arch.

[Conversion Therapy for HER2-Positive Metastatic Breast Cancer with Intrathoracic Lymph Node Metastasis].

A 42-year-old woman consulted our hospital with chief complaints of a right breast mass and pain. Based on needle biopsy of the breast tumor, the pathological diagnosis was invasive ductal carcinoma(scirrhous type), which tested positive for estrogen, progesterone, and HER2 receptor. PET-CT(FDG)showed intrathoracic lymph node metastasis. After several tests, she received a diagnosis of cT2N1M1(LYM), Stage Ⅳ breast cancer. She received pertuzumab, trastuzumab, and docetaxel treatments. After chemotherapy, the intrathoracic lymph node and breast tumors were not observed. She underwent mastectomy and axillary lymph node dissection. The pathological diagnosis showed a complete response after surgery. The patient's postoperative course was uneventful; she had received radiotherapy and anti-HER2 therapy. Twenty-three months after the surgery, no recurrence was observed. Herein, we report successful treatment of Stage Ⅳ breast cancer with conversion therapy.

The association between brain morphological development and the quality of general movements.

AIM: To clarify the morphologic characteristics of the brain, which are the foundation of the emergence of general movements (GMs) in very-low-birth-weight infants. STUDY DESIGN: Prospective cohort study. GMs were scored according to a semiquantitative scoring system: the GMs optimality score (GMOS) at preterm and term ages. Brain magnetic resonance imaging (MRI) at term-equivalent age was scored using a validated scoring system (MRI score). We examined the relationship between the two scores by multiple regression analysis with relevant clinical background. SUBJECTS: We included 50 very-low-birth-weight infants cared for at Oita University Hospital from August 2012 to August 2018 who underwent MRI and GMs assessment. Their median gestational age and birth weight were 29w2d and 1145 g, respectively. RESULTS: The MRI score and systemic steroid administration were related to preterm GMOS, and the MRI score was related to term GMOS. The component cerebellum score and cortical grey matter score of the MRI score were associated with preterm GMOS, and the cerebellum and the cerebral white matter scores were associated with term GMOS. CONCLUSION: The quality of GMs was associated with brain morphological development. The co-evaluation of GMs and brain morphology leads to accurate developmental prediction.

Medical certification reduces the number of children requiring allergen elimination diets for school lunches.

BACKGROUND: Following the increase in the number of children with food allergies, support systems are now required for school lunches, but a large-scale factual investigation has not been carried out. OBJECTIVE: We evaluated the features of elimination diet due to food allergy and the support system in kindergartens and schools. METHODS: A prefecture-based questionnaire survey regarding measures for food allergies in school lunches of all kindergartens, public elementary schools, and public junior high schools (631 facilities) was conducted in Oita Prefecture, Japan. RESULTS: The recovery rate of the questionnaire was 99.5%, which included 106,008 students in total. A total of 1,562 children (1.5%) required elimination diets. The rate of children on elimination diets in kindergartens and elementary/junior high schools that required medical certification by a physician was 1.2% (324 among 27,761 children), which was significantly lower than the 1.8% of children (1,227 among 68,576 students) on elimination diets at the request of guardians without the need for medical certification (p < 0.0001). A total of 43.9% of the kindergartens and schools said that they would contact guardians if symptoms were observed after accidental ingestion, while a low 8.1% stated that they provided support to children themselves, including the administration of adrenaline auto-injectors. CONCLUSION: Medical certification reduces the number of children requiring elimination diets, but it has not been adequately implemented. Furthermore, waiting to contact guardians after symptoms are observed may lead to the delayed treatment of anaphylaxis. Cooperation between physicians and teachers is desired to avoid the overdiagnosis and undertreatment of children with food allergies.

Epidemiologic Research on Malformations Associated with Cleft Lip and Cleft Palate in Japan.

To investigate malformations associated with cleft lip and cleft palate, we conducted surveys at neonatal intensive care units (NICUs) and other non-NICU facilities and to determine whether there are differences among facilities. The regional survey investigated NICU facilities located in Oita Prefecture, including 92 patients with cleft lip and palate (CLP) or cleft palate (CP) that occurred between 2004 and 2013, and the national survey investigated oral surgery, plastic surgery, and obstetrics and gynecology facilities located in Japan, including 16,452 patients with cleft lip (CL), CLP, or CP that occurred since 2000. The incidence per 10,000 births was 4.2, 6.2, and 2.8 for CL, CLP, and CP, respectively, according to the national survey, and 6.3 and 2.9 for CLP and CP, respectively according to the regional survey. These results indicated comparable incidences between the two surveys. In contrast, when the survey results on malformations associated with CLP and CP according to the ICD-10 classification were compared between the national survey conducted at oral surgery or plastic surgery facilities and the regional survey conducted at NICU facilities, the occurrence of associated malformations was 19.8% vs. 41.3% for any types of associated malformation, 6.8% vs. 21.7% for congenital heart disease, and 0.5% vs. 16.3% for chromosomal abnormalities. These results indicated that the incidences of all of these associated malformations were significantly greater in the survey conducted at NICU facilities and similar to the findings from international epidemiological surveys. When comparing the survey conducted at obstetrics facilities vs. NICU facilities, the occurrence of associated malformations was similar results as above. The incidence of CLP and CP was not different between surveys conducted at NICU facilities vs. non-NICU facilities; however, when conducting surveys on associated malformations, it is possible to obtain accurate epidemiological data by investigating NICU facilities where detailed examinations are thoroughly performed.

Anxiolytic-like effect of inhalation of essential oil from Lavandula officinalis: investigation of changes in 5-HT turnover and involvement of olfactory stimulation.

Essential oil extracted from Lavandula officinalis (LvEO) has a long history of usage in anxiety alleviation with good evidence to support its use. However, findings and information regarding the exact pathway involved and mechanism of action remain inconclusive. Therefore, we aimed to (1) reveal the influence of olfactory stimulation, and (2) determine whether the serotonergic system is involved in the anxiolytic effect of LvEO when it is inhaled. To this end, we first compared the anxiety-related behaviors of normosmic and anosmic mice. LvEO inhalation caused notable elevation in anxiety-related parameters with or without olfactory perception, indicating that olfactory stimulation is not necessarily required for LvEO to be effective. Neurochemical analysis of the serotonin (5-HT) turnover rate, accompanied by EPM testing, was then performed. LvEO significantly increased the striatal and hippocampal levels of 5-HT and decreased turnover rates in accordance with the anxiolytic behavioral changes. These results, together with previous findings, support the hypothesis that serotonergic neurotransmission plays a certain role in the anxiolytic properties of LvEO.

Enantiomeric separation of tolperisone and eperisone by reversed-phase HPLC with cellulose tris(3-chloro-4-methylphenylcarbamate)-coated chiral column.

Enantiomeric separations of centrally acting muscle relaxants, that is, tolperisone (TOL) and eperisone (EP), that are marketed as racemates were investigated by reversed-phase high-performance liquid chromatography (HPLC) on a polysaccharide-based chiral column. Both TOL and EP are basic drugs because they contain a tertiary amino group and have similar chemical structures with the exception of the p-methylphenyl and p-ethylphenyl groups in TOL and EP, respectively. A reversed-phase chiral column, that is, a Chiralcel OZ-RH column, which bears cellulose tris(3-chloro-4-methylphenylcarbamate) as the chiral moiety, was effective for the enantiomeric separation of TOL and EP enantiomers. The separation factor and resolution values obtained for TOL were 1.22 and 1.66, respectively, and those for EP were 1.21 and 2.24, respectively, using a 20 mm ammonium acetate in H2 O (pH 8.0 and 7.0, respectively)-CH3 CN (70:30) mobile phase. Using the proposed HPLC conditions, it was found that (R)-TOL eluted faster than (S)-TOL, as revealed by the optical rotation and circular dichroism spectroscopy. In contrast, EP was easily racemized under the experimental conditions, and hence, the elution order was not determined.

Organ accumulation in mice after inhalation of single or mixed essential oil compounds.

Essential oils are composed of multiple components. It is thought that the effect of essential oils is due to specific component ratios, which may differ from the original ratio when the essential oil is absorbed. However, very little detailed research exists in this area. We studied the distribution of essential oil components after inhalation of single and mixed components in mice. This research was done using four main components of Alpinia zerumbet (Pers.) B. L. Burtt. and R. M. Sm.: α-pinene, p-cymene, 1,8-cineole, and limonene. After inhalation of single or mixed components for 90 min, component levels in the brain and liver of mice were measured. The results indicated that the amount of α-pinene in the brain and liver was twofold greater after mixed-component inhalation than that after single-component inhalation. In a comparison of the components of the mixed inhalation, the ratio of α-pinene increased to about three times that of 1,8-cineole. It is thought that the absorption via the nasal mucus greatly influences this phenomenon. The results of this investigation of the bodily distribution of essential oil volatile components may provide clues for elucidating their action.

Effects of inhaled lavender essential oil on stress-loaded animals: changes in anxiety-related behavior and expression levels of selected mRNAs and proteins.

Inhalation of various essential oils elicits behavioral changes as a consequence of a complex centrally coordinated response. To understand the molecular mechanisms of action of aromatic compounds on emotional responses, we evaluated the stress-induced changes in mouse brain and the efficacy of inhaled essential oil from Lavandula officinalis (LvEO) using two approaches: a behavioral test, and examining the expression levels of selected genes {fast nerve growth factor receptor (NGFR) mRNA, activity regulated cytoskeletal-associated protein (Arc) mRNA} and proteins {galactokinase 1 (GLK1) and brain-derived neurotrophic factor (BDNF)}. Animals were randomly divided into 4 groups depending on the treatment given: stress (-)/H20, stress (-)/LvEO, stress (+)/H2O, and stress (+)/LvEO group. For behavioral testing, using an elevated plus-maze test, significant anxiolytic-like effects were seen in both the stress (-)/LVEO and stress (+)/LvEO groups, indicating that LvEO exerts anxiolytic-like effects regardless of the administration of water immersion stress. On expression analysis, the levels of NGFR and Arc mRNA were significantly lower in animals subjected to stress. Inhalation of LvEO, however, reversed this change, thus suggesting that LvEO negates the impact of stress on gene expression levels. Meanwhile, significant decreases in expression levels were also observed in the stress (-)/LvEO group, which implies that LvEO, when given in a stress-free situation, may act as a stress stimulus. Taken together, our data suggest that inhalation of LvEO exerts bidirectional influences in the central nervous system (CNS) of animals, either attenuating the effects of stress or acting as a stressor, depending on the subject state.

Components of essential oils extracted from leaves and shoots of abies species in Japan.

The essential oils extracted from the leaves and the shoots of five Abies species (Pinaceae) growing in Japan, i.e., A. firma, A. homolepis, A. veitchii, A. mariesii, and A. sachalinensis, were characterized by GC-FID and GC/MS analyses. The yields of the essential oils extracted from A. sachalinensis were the highest among them. A significant amount of α-pinene was contained in the essential oils of all the Abies species examined. In A. homolepis and A. veitchii, significant differences in the content of the essential oils were found depending on whether these were extracted from the leaves or from the shoots. Regarding the enantiomeric ratio of α-pinene, the (+)-enantiomer was predominant in the oil extracted from the leaves of A. firma, while (-)-α-pinene was present in higher amounts in the oils of A. veitchii (leaves and shoots), A. mariesii (leaves and shoots), and A. sachalinensis (shoots). The fact that there may be a quantitative and qualitative difference in the components of the essential oils extracted from the different parts of a plant was investigated by cluster analysis.

Interspecies comparison of chemical composition and anxiolytic-like effects of lavender oils upon inhalation.

Essential oils have traditionally been used for decades to alleviate the symptoms of various mental problems. In terms of anxiolytic-like properties, lavender oil is probably the most commonly used and best-studied essential oil. Although there is compositional variance among the oils extracted from different origins, there have been few studies performed to date to investigate how these differences affect the expression of anxiolytic-like activity. This paper discusses the interspecies differences and contributions of the main constituents in the expression of anxiolytic-like effects upon inhalation, as assessed in mice by the elevated-plus maze test, by comparing the essential oils from six different species of Lavandula. The results showed qualitative and quantitative variations in the tested oils, which results in significant differences in their anxiolytic-like activities. Our findings also suggest that linalyl acetate (LA) works synergistically with linalool (LO) and that the presence of both LA and LO is essential for the whole oil to work as an inhaled anti-anxiety agent.