Association between low MCV in early pregnancy and perinatal mental health in the Japan Environment and Children's Study and the possible effect of iron deficiency.

BACKGROUND: Postpartum anemia and iron deficiency are associated with postpartum depression. This study investigated the association between a low mean corpuscular volume (MCV) without anemia (which implies early-stage iron deficiency) in early pregnancy and perinatal mental health outcomes. METHODS: The fixed data from the Japan Environment and Children's Study (JECS), a Japanese nationwide birth cohort, were used. Perinatal mental health was assessed using the Kessler 6-item psychological distress scale (K6) in mid-pregnancy and the Edinburgh Postnatal Depression Scale (EPDS) at 1- and 6-months postpartum. RESULTS: Among the 3635 women with MCVs <85 fL in early pregnancy, the proportions of women with K6 scores ≥13 in mid-pregnancy and EPDS scores ≥9 at 1- and 6-months postpartum were 2.7 %, 12.8 %, and 9.9 %, respectively, compared with the 33,242 women with MCVs ≥85 fL at 1.9 %, 11.9 %, and 9.0 %, respectively. Multivariate logistic regression models showed that an MCV <85 in early pregnancy was associated with a K6 score ≥ 13 in mid-pregnancy and an EPDS score ≥ 9 at 1- and 6-months postpartum (adjusted odds ratio (95 % confidence interval): 1.48 (1.16-1.87), 1.14 (1.01-1.28), and 1.09 (0.95-1.24), respectively). LIMITATIONS: Low MCV values do not necessarily represent iron deficiency. Ferritin, currently the best indicator of iron deficiency, was not measured in the JECS. CONCLUSIONS: This study results suggest that a low MCV without anemia in early pregnancy is associated with a slightly increased risk of perinatal mental health deterioration.

Effect of Diluents on Active Pharmaceutical Ingredient Loss Until Patients Ingest Powder Formulation.

In powder formulations, it is a problem that the required therapeutic dose is not obtained because of loss of the active pharmaceutical ingredient (API). In this study, we investigated three types of lactose diluents, which are widely used as pharmaceutical excipients, for dispensing prednisolone powder. Extra-fine crystalline lactose, commonly used as a diluent in compounding powder formulations, was used as a comparison. The effect of lactose on the API loss rate was examined by analyzing the amount of prednisolone in the powder formulation taken out of a single-dose package after dispensing. The results showed that Dilactose-F had the lowest API loss rate (22%), followed by powder lactose (37.8%), extra-fine crystalline lactose (45.9%), and crystal form lactose (48.6%), indicating that the use of Dilactose-F as a diluent significantly improved API loss when compounding the powder formulation. Because each mixture of commercial prednisolone powder and lactose was within acceptable uniformity and loss rate before packaging, we considered that API loss occurred when the powder was taken out of the single-dose package before patients ingested them. Then, the physical properties of these lactose types affecting the API loss rate were examined. Strong correlation was not found between flowability and the API loss rate, but particle size distribution and bulk density were strongly correlated with the API loss rate. Furthermore, Dilactose-F, which showed the lowest API loss rate, did not show an exothermic peak due to epimerization to anhydrous ß -lactose in differential scanning calorimetry and showed a peak specific to ß -lactose in powder X-ray diffractometer. These results suggested that in powder compounding where the API content is low, the physical properties of lactose, such as particle size distribution, bulk density, and crystalline form, are intricately related to API loss.

Stent Graft of Pseudoaneurysm Rupture After Subtotal Stomach-preserving Pancreaticoduodenectomy.

BACKGROUND/AIM: Pseudoaneurysm rupture (PR) after subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) is a potentially fatal complication. PATIENTS AND METHODS: This study included 122 patients who underwent SSPPD at the Matsuyama Red Cross Hospital between January 2016 and December 2021. RESULTS: PR occurred in five patients (4.1%) after SSPPD. Preoperative diagnoses were cancers of the pancreatic head, distal bile duct, and gallbladder. All patients had postoperative Grade B or C pancreatic fistulas. PR occurred on postoperative days 8, 13, 20, 45, and 46. Bleeding sites were at the gastroduodenal artery transection, left gastric artery, and right hepatic artery. Four patients underwent peripheral stent graft placement, and one underwent haemostasis by coiling. Stent grafts for the gastroduodenal artery transected stamp were placed in the common hepatic artery, and in the superior mesenteric artery for PR in the right hepatic artery. All patients who underwent stent graft placement were treated with antiplatelet therapy; no complications or stent occlusion were observed in these patients. However, two patients died of cancer recurrence, 4 and 8 months after stent graft placement. The longest survival post stent graft placement was 50 months. CONCLUSION: Peripheral stent graft placement for the treatment of PR after SSPPD can maintain peripheral blood flow and haemostasis.

Development of Rat Caries-Induced Pulpitis Model for Vital Pulp Therapy.

Rodent animal models for vital pulp therapy are commonly used in dental research because their tooth anatomy and cellular processes are similar to the anatomy and processes in humans. However, most studies have been conducted using uninfected sound teeth, which makes it difficult to adequately assess the inflammatory shift after vital pulp therapy. In the present study, we aimed to establish a caries-induced pulpitis model based on the conventional rat caries model and then evaluate inflammatory changes during the wound-healing process after pulp capping in a model of reversible pulpitis induced by carious infection. To establish the caries-induced pulpitis model, the pulpal inflammatory status was investigated at different stages of caries progression by immunostaining targeted to specific inflammatory biomarkers. Immunohistochemical staining revealed that both Toll-like receptor 2 and proliferating cell nuclear antigen were expressed in moderate and severe caries-stimulated pulp, indicating that an immune reaction occurred at both stages of caries progression. M2 macrophages were predominant in moderate caries-stimulated pulp, whereas M1 macrophages were predominant in the severe caries-stimulated pulp. Pulp capping in teeth with moderate caries (i.e., teeth with reversible pulpitis) led to complete tertiary dentin formation within 28 d after treatment. Impaired wound healing was observed in teeth with severe caries (i.e., teeth with irreversible pulpitis). During the wound-healing process in reversible pulpitis after pulp capping, M2 macrophages were predominant at all time points; their proliferative capacity was upregulated in the early stage of wound healing compared with healthy pulp. In conclusion, we successfully established a caries-induced pulpitis model for studies of vital pulp therapy. M2 macrophages have an important role in the early stages of the wound-healing process in reversible pulpitis.

Novel Functional Peptide for Next-Generation Vital Pulp Therapy.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography-tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

Formation and evolution of carbonaceous asteroid Ryugu: Direct evidence from returned samples.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide-bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu's parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of <1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate that Ryugu's parent body formed ~2 million years after the beginning of Solar System formation.

Influence of lower extremity rotation on knee kinematics in single-leg landing.

OBJECTIVES: Although the rotation of lower extremities has gained increasing recognition as a risk factor for anterior cruciate ligament (ACL) injury. This study clarified the influence of lower extremity rotation on the knee during single-leg landing. DESIGN AND SETTING: We recruited 30 students to perform single-leg landing from a height of 30 cm with their lower extremities in neutral, and externally and internally rotated. The knee abduction, flexion angles, and abduction angular velocity were measured. Furthermore, the abduction angle was analyzed at knee flexion angles of 15°, 20°, 25°, and 30° and compared among the three conditions using a repeated measures analysis of variance with Bonferroni post hoc tests. RESULTS: The maximum abduction angle was significantly greater when internally rotated than in the neutral. The maximum abduction angular velocity was significantly greater in the internally rotated compared to in the neutral. Finally, the abduction angle at a knee flexion angle of 30° was significantly greater when internally rotated compared to in the neutral. CONCLUSION: Rotation of the lower extremities affects knee kinematics, and landing on a knee that is internally rotated may increase the risk of ACL injury.

CA19-9 Reduction After 4 Months of Treatment Is a Prognostic Factor for Locally Advanced Pancreatic Cancer.

BACKGROUND/AIM: Carbohydrate antigen 19-9 (CA19-9) levels may aid in the determination of subsequent treatment in patients with unresectable locally-advanced pancreatic cancer (LAPC) treated with chemotherapy. However, the relationship between the timing and magnitude of CA19-9 changes and clinical outcomes remains unclear. This study was conducted to identify the timing and magnitude of CA19-9 changes, which are most strongly associated with outcomes in LAPC patients. PATIENTS AND METHODS: We retrospectively analyzed consecutive LAPC patients treated with gemcitabine plus nab-paclitaxel (GnP) or modified FOLFIRINOX (mFFX) as the first-line chemotherapy between March 2014 and December 2018 in our hospital. Multivariate analyses were performed to identify prognostic factors of chemotherapy in LAPC. RESULTS: Ninety-four patients were included (GnP/mFFX: 72/22). The median overall survival was 20.3 months, and the median progression-free survival was 8.8 months. CA19-9 values before treatment did not affect prognosis. However, CA19-9 <100 U/ml or more than a 70% reduction in CA19-9 four months after commencing treatment was associated with a good prognosis (hazard ratio=0.17; 95% confidence interval=0.09-0.33; p<0.01). CONCLUSION: CA19-9 values 4 months after commencing treatment are a significant prognostic factor in LAPC patients undergoing chemotherapy.

Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study.

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.

Comparison of the Antiemetic Effect of Aprepitant/granisetron and Palonosetron Combined with Dexamethasone in Gynecological Cancer Patients Treated with Paclitaxel and Carboplatin Combination Regimen.

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Modelling the invasion of human small intestinal epithelial-like cells by Salmonella enterica Typhimurium and Listeria monocytogenes using Bayesian inference.

To develop a mechanistic bacterial dose-response model, based on the concept of Key Events Dose-Response Framework (KEDRF), this study aimed to investigate the invasion of intestinal model cells (Caco-2) by Salmonella Typhimurium and Listeria monocytogenes and described the behaviour of both pathogens as a mathematical model using Bayesian inference. Monolayer-cultured Caco-2 cells (approximately 105 cells) were co-cultured with various concentrations (103 -107 colony forming unit [CFU] ml-1 ) of Salm. Typhimurium and L. monocytogenes for up to 9 h to investigate the invasion of the pathogens into the Caco-2 cells. While an exposure of ≥103 CFU ml-1 of Salm. Typhimurium initiated the invasion of Caco-2 cells within 3 h, much less exposure (102 CFU ml-1 ) of L. monocytogenes was sufficient for invasion within the same period. Furthermore, while the maximum number of invading Salm. Typhimurium cells reached by approximately 103 CFU cm-2 for 6-h exposure, the invading maximum numbers of L. monocytogenes cells increased by approximately 106 CFU cm-2 for the same exposure period. The invasion kinetics of both the pathogens was successfully described as an asymptotic exponential mathematical model using Bayesian inference. The developed pathogen invasion model allowed the estimation of probability of Salm. Typhimurium and L. monocytogenes infection, based on the physiological natures of digestion process, which was comparable to the published dose-response relationship. The invasion models developed in the present study will play a key role in the development of an alternative pathogen dose-response model based on KEDRF concept.

Impact of Histological Features on Adjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Carcinoma.

BACKGROUND/AIM: This study evaluated the efficacy of adjuvant chemotherapy (AC) for intraductal papillary mucinous carcinoma (IPMC). PATIENTS AND METHODS: We retrospectively analyzed patients who underwent pancreatectomy for invasive IPMC from January 2007 to June 2020. We evaluated outcomes of AC in the entire cohort and in patients with known prognostic factors. RESULTS: A total of 51 patients with invasive IPMC underwent surgery, of which 35 received AC. In the entire cohort, there was no significant difference in median overall survival (OS) between the AC and surgery alone (SA) group [hazard ratio (HR)=0.54; p=0.232]. For patients with poorly differentiated adenocarcinoma, median OS was significantly longer in the AC group (HR=0.27; p=0.022). For patients with lymph node metastasis, median OS was significantly higher in the AC group (HR=0.07; p<0.001). CONCLUSION: AC may be effective for selected invasive IPMC patients.

Nosocomial infection with rotavirus vaccine strain in paediatric patients with immunodeficiency.

In infants with immunodeficiency, rotavirus (RV) vaccines can be continuously excreted in stool. We analysed nosocomial infection with RV vaccine strain in immunodeficient paediatric patients. RV1 RNAs were detected in stool and serum samples from case A, who was vaccinated with RV1, and case B, who was not. PAGE analysis of serial stool samples of case A revealed several rearrangements of the RV genome. In case B, the only band pattern detected was the same as a rearrangement detected in case A at the same time. In summary, RV vaccination of infants with immunodeficiency poses a risk of nosocomial infections.

Enhanced gyrotropic birefringence and natural optical activity on electromagnon resonance in a helimagnet.

Spontaneous symmetry breaking in crystalline solid often produces exotic nonreciprocal phenomena. As one such example, the unconventional optical rotation with nonreciprocity, which is termed gyrotropic birefringence, is expected to emerge from the magnetoelectric coupling. However, the fundamental nature of gyrotropic birefringence remains to be examined. Here w`e demonstrate the gyrotropic birefringence enhanced by the dynamical magnetoelectric coupling on the electrically active magnon resonance, i.e. electromagnon, in a multiferroic helimagnet. The helical spin order having both polarity and chirality is found to cause the giant gyrotropic birefringence in addition to the conventional gyrotropy, i.e. natural optical activity. It is demonstrated that the optical rotation of gyrotropic birefringence can be viewed as the nonreciprocal rotation of the optical principal axes, while the crystallographic and magnetic anisotropies are intact. The independent control of the nonreciprocal linear (gyrotropic birefringence) and circular (natural optical activity) birefringence/dichroism paves a way for the optically active devices.

Magneto-optical spectroscopy on Weyl nodes for anomalous and topological Hall effects in chiral MnGe.

Physics of Weyl electrons has been attracting considerable interests and further accelerated by recent discoveries of giant anomalous Hall effect (AHE) and topological Hall effect (THE) in several magnetic systems including non-coplanar magnets with spin chirality or small-size skyrmions. These AHEs/THEs are often attributed to the intense Berry curvature generated around the Weyl nodes accompanied by band anti-crossings, yet the direct experimental evidence still remains elusive. Here, we demonstrate an essential role of the band anti-crossing for the giant AHE and THE in MnGe thin film by using the terahertz magneto-optical spectroscopy. The low-energy resonance structures around ~ 1.2 meV in the optical Hall conductivity show the enhanced AHE and THE, indicating the emergence of at least two distinct anti-crossings near the Fermi level. The theoretical analysis demonstrates that the competition of these resonances with opposite signs is a cause of the strong temperature and magnetic-field dependences of observed DC Hall conductivity. These results lead to the comprehensive understanding of the interplay among the transport phenomena, optical responses and electronic/spin structures.

Linker Threonine-phosphorylated Smad2/3 Is a Biomarker of Colorectal Neoplastic Stem-like Cells that Correlates With Carcinogenesis.

BACKGROUND/AIM: This study analysed threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr) expression and investigated whether pSmad2/3L-Thr is related to the transition from human colorectal adenoma (CRA) to carcinoma (CRC). MATERIALS AND METHODS: Immunofluorescent staining was performed forß-catenin, p53, CDK4, Ki67, Sox9, aldehyde dehydrogenase (ALDH) 1, and pSmad2/3L-Thr. RESULTS: We analysed specimens of diffuse p53-positive CRCs arising from p53-negative CRAs. Percentage of p53, nuclear ß-catenin, Ki67, CDK4, and pSmad2/3L-Thr-positive cells at the site of CRCs was significantly higher than that at the site of CRAs. At the site of normal colorectal mucosae, few epithelial cells were stained positively for pSmad2/3L-Thr. At the site of CRCs, pSmad2/3L-Thr-positive cells showed co-localization with p53, nuclear ß-catenin, and ALDH1. At any site, pSmad2/3L-Thr-positive cells showed co-localization with CDK4. CONCLUSION: pSmad2/3L-Thr correlates with human CRC carcinogenesis, and pSmad2/3L-Thr-positive cells show human colorectal stem cell-like and cancer stem cell characteristics.

Orbital haematoma after orbital fracture repair using silicone, polytetrafluorethylene, and poly-L-lactic acid/hydroxyapatite implants.

The purpose of this paper was to report the incidence of orbital haematoma formation following the repair of orbital fractures with silicone, polytetrafluorethylene (PTFE), and poly-L-lactic acid/hydroxyapatite (PLLA/HA) implants. This retrospective review examined 234 patients (235 sides) who underwent repair of orbital wall fractures over a six-year period. Of these, 36 patients received a silicone sheet; 49 patients received a silicone sheet with superimposed PTFE implant; and 149 patients (150 sides) received PTFE with or without an underlying PLLA/HA implant. Orbital haematomas were documented in 13 out of 36 patients (36.1%) who underwent fracture repair with a silicone sheet; seven out of 49 patients (14.3%) who had a silicone sheet with a superimposed PTFE implant; and three out of 150 sides (2.0%) with PTFE with or without underlying PLLA/HA. The difference in incidence of orbital haematoma formation was significant among the groups (p < 0.001, Pearson's chi squared test). In the silicone sheet group, haematomas formed within two weeks of surgery in 11 patients (84.6%). In the silicone sheet with superimposed PTFE implant group, five patients (71.4%) developed orbital haematomas no earlier than after two weeks postoperatively. This study showed that the incidence of orbital haematoma formation following orbital fracture repair is different among the implant materials. The use of PTFE and PLLA/HA implants may minimise this complication.

Recent advances in SmFe12-based permanent magnets.

To realize a sustainable society, 'green technology' with low (or even zero) CO2 emissions is required. A key material in such technology is a permanent magnet because it is utilized for electric-power conversion in several applications including electric vehicles (EVs), hybrid EVs (HEVs), and turbines for wind power generation. To realize highly efficient electric-power conversion, a stronger permanent magnet than Nd-Fe-B is necessary. One potential candidate is a Fe-rich SmFe12-based compound with a ThMn12 structure. In this paper, the phase stability, structure, and intrinsic and extrinsic magnetic properties in both film and bulk forms are reviewed. Based on these results, a possible way to realize a strong SmFe12-based permanent magnet in bulk form is discussed.