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Abstract Background Crescentic glomerulonephritis with syphilis infection is rare, and the mechanism underlying the formation of glomerular capillary wall damage-induced crescent has not been elucidated. Case presentation A 62-year-old Japanese male showed edema, eruption, and rapid deterioration of the renal function after an acute syphilis infection. A renal biopsy showed crescentic glomerulonephritis with C3 deposition in the glomerular capillary wall, and immunostaining for anti-Treponema pallidum antibody was weakly positive in some interstitium and one glomerulus. Electron microscopy revealed the presence of string-shaped structures in the glomerular capillary walls. After treatment with penicillin followed by prednisolone, the renal function and urinary abnormalities, including Treponema pallidum protein, disappeared. Conclusions Crescentic glomerulonephritis associated with syphilis showed a string-shaped deposition in the glomerular capillary and urinary Treponema pallidum protein excretion, and was effectively treated with penicillin and prednisolone.

To better understand the molecular genetics of the Shiga toxin type 2 subunit A gene (stx2A gene), we collected many subtypes of stx2A genes and performed detailed molecular evolutionary analyses of the gene. To achieve the aim of the study, we used several bioinformatics technologies, including time-scaled phylogenetic analyses, phylogenetic distance analyses, phylodynamics analyses, selective pressure analyses, and conformational epitope analyses. A time-scaled phylogeny showed that the common ancestor of the stx2A gene dated back to around 18,600 years ago. After that, the gene diverged into two major lineages (Lineage 1 and 2). Lineage 1 comprised the stx2a–2d subtypes, while Lineage 2 comprised the stx2e, 2g, 2h, and 2o subtypes. The evolutionary rates of the genes were relatively fast. Phylogenetic distances showed that the Lineage 2 strains had a wider genetic divergence than Lineage 1. Phylodynamics also indicated that the population size of the stx2A gene increased after the 1930s and spread globally. Moreover, negative selection sites were identified in the Stx2A proteins, and these sites were diffusely distributed throughout the protein. Two negative selection sites were located adjacent to an active site of the common Stx2A protein. Many conformational epitopes were also estimated in these proteins, while no conformational epitope was found adjacent to the active site. The results suggest that the stx2A gene has uniquely evolved and diverged over an extremely long time, resulting in many subtypes. The dominance of the strains belonging to Lineage 1 suggests that differences in virulence may be involved in the prosperity of the offspring. Furthermore, some subtypes of Stx2A proteins may be able to induce effective neutralizing antibodies against the proteins in humans.

The ectopic overexpression of developmental regulator (DR) genes has been reported to improve the transformation in recalcitrant plant species because of the promotion of cellular differentiation during cell culture processes. In other words, the external plant growth regulator (PGR) application during the tissue and cell culture process is still required in cases utilizing DR genes for plant regeneration. Here, the effect of Arabidopsis BABY BOOM (BBM) and WUSCHEL (WUS) on the differentiation of tobacco transgenic cells was examined. We found that the SRDX fusion to WUS, when co-expressed with the BBM-VP16 fusion gene, significantly influenced the induction of autonomous differentiation under PGR-free culture conditions, with similar effects in some other plant species. Furthermore, to understand the endogenous background underlying cell differentiation toward regeneration, phytohormone and RNA-seq analyses were performed using tobacco leaf explants in which transgenic cells were autonomously differentiating. The levels of active auxins, cytokinins, abscisic acid, and inactive gibberellins increased as cell differentiation proceeded toward organogenesis. Gene Ontology terms related to phytohormones and organogenesis were identified as differentially expressed genes, in addition to those related to polysaccharide and nitrate metabolism. The qRT-PCR four selected genes as DEGs supported the RNA-seq data. This differentiation induction system and the reported phytohormone and transcript profiles provide a foundation for the development of PGR-free tissue cultures of various plant species, facilitating future biotechnological breeding.

Sarcopenic dysphagia is characterized by weakness of swallowing-related muscles associated with whole-body sarcopenia. As the number of patients with sarcopenia increases with the aging of the world, the number of patients with sarcopenic dysphagia is also increasing. The prevalence of sarcopenic dysphagia is high in the institutionalized older people and in patients hospitalized for pneumonia with dysphagia in acute care hospitals. Prevention, early detection and intervention of sarcopenic dysphagia with rehabilitation nutrition are essential. The diagnosis of sarcopenic dysphagia is based on skeletal and swallowing muscle strength and muscle mass. A reliable and validated diagnostic algorithm for sarcopenic dysphagia is used. Sarcopenic dysphagia is associated with malnutrition, which leads to mortality and Activities of Daily Living (ADL) decline. The rehabilitation nutrition approach improves swallowing function, nutrition status, and ADL. A combination of aggressive nutrition therapy to improve nutrition status, dysphagia rehabilitation, physical therapy, and other interventions can be effective for sarcopenic dysphagia. The rehabilitation nutrition care process is used to assess and problem solve the patient’s pathology, sarcopenia, and nutrition status. The simplified rehabilitation nutrition care process consists of a nutrition cycle and a rehabilitation cycle, each with five steps: assessment, diagnosis, goal setting, intervention, and monitoring. Nutrition professionals and teams implement the nutrition cycle. Rehabilitation professionals and teams implement the rehabilitation cycle. Both cycles should be done simultaneously. The nutrition diagnosis of undernutrition, overnutrition/obesity, sarcopenia, and goal setting of rehabilitation and body weight are implemented collaboratively.

Abstract Chimerism analysis is a surrogate indicator of graft rejection or relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Although short tandem repeat PCR (STR-PCR) is the usual method, limited sensitivity and technical variability are matters of concern. Quantitative PCR-based methods to detect single nucleotide polymorphisms (SNP-qPCR) are more sensitive, but their informativity and quantitative accuracy are highly variable. For accurate and sensitive chimerism analysis, a set of KMR kits (GenDx, Utrecht, Netherlands), based on detection of insertions/deletions (indels) by qPCR, have been developed. Here, we investigated informativity and validated the accuracy of KMR kits in Japanese donor/recipient pairs and virtual samples of DNA mixtures representative of Japanese genetic diversity. We found that at least one recipient-specific marker among 39 KMR-kit markers was informative in all of 65 Japanese donor/recipient pairs. Moreover, the percentage of recipient chimerism estimated by KMRtrack correlated well with ratios of mixed DNA in virtual samples and with the percentage of chimerism in HSCT recipients estimated by STR-PCR/in-house SNP-qPCR. Moreover, KMRtrack showed better sensitivity with high specificity when compared to STR-PCR to detect recipient chimerism. Chimerism analysis with KMR kits can be a standardized, sensitive, and highly informative method to evaluate the graft status of HSCT recipients.

RNA vaccines are applicable to the treatment of various infectious diseases via the inducement of robust immune responses against target antigens by expressing antigen proteins in the human body. The delivery of messenger RNA by lipid nanoparticles (LNPs) has become a versatile drug delivery system used in the administration of RNA vaccines. LNPs are widely considered to possess adjuvant activity that induces a strong immune response. However, the properties of LNPs that contribute to their adjuvant activity continue to require clarification. To characterize the relationships between the lipid composition, particle morphology, and adjuvant activity of LNPs, the nanostructures of LNPs and their antibody production were evaluated. To simply compare the adjuvant activity of LNPs, empty LNPs were subcutaneously injected with recombinant proteins. Consistent with previous research, the presence of ionizable lipids was one of the determinant factors. Adjuvant activity was induced when a tiny cholesterol assembly (cholesterol-induced phase, ChiP) was formed according to the amount of cholesterol present. Moreover, adjuvant activity was diminished when the content of cholesterol was excessive. Thus, it is plausible that an intermediate structure of cholesterol (not in a crystalline-like state) in an intra-particle space could be closely related to the immunogenicity of LNPs.

To better understand the evolution of the SARS-CoV-2 Omicron subvariants, we performed molecular evolutionary analyses of the spike (S) protein gene/S protein using advanced bioinformatics technologies. First, time-scaled phylogenetic analysis estimated that a common ancestor of the Wuhan, Alpha, Beta, Delta variants, and Omicron variants/subvariants diverged in May 2020. After that, a common ancestor of the Omicron variant generated various Omicron subvariants over one year. Furthermore, a chimeric virus between the BM.1.1.1 and BJ.1 subvariants, known as XBB, diverged in July 2021, leading to the emergence of the prevalent subvariants XBB.1.5 and XBB.1.16. Next, similarity plot (SimPlot) data estimated that the recombination point (breakpoint) corresponded to nucleotide position 1373. As a result, XBB.1.5 subvariants had the 5′ nucleotide side from the breakpoint as a strain with a BJ.1 sequence and the 3′ nucleotide side as a strain with a BM.1.1.1 sequence. Genome network data showed that Omicron subvariants were genetically linked with the common ancestors of the Wuhan and Delta variants, resulting in many amino acid mutations. Selective pressure analysis estimated that the prevalent subvariants, XBB.1.5 and XBB.1.16, had specific amino acid mutations, such as V445P, G446S, N460K, and F486P, located in the RBD when compared with the BA.4 and BA.5 subvariants. Moreover, some representative immunogenicity-associated amino acid mutations, including L452R, F486V, R493Q, and V490S, were also found in these subvariants. These substitutions were involved in the conformational epitopes, implying that these mutations affect immunogenicity and vaccine evasion. Furthermore, these mutations were identified as positive selection sites. These results suggest that the S gene/S protein Omicron subvariants rapidly evolved, and mutations observed in the conformational epitopes may reduce the effectiveness of the current vaccine, including bivalent vaccines such as mRNA vaccines containing the BA.4/BA.5 subvariants.

During hemodialysis (HD), blood pressure (BP) changes are frequently observed. However, the mechanism of BP changes during HD has not been fully clarified. The cardio–ankle vascular index (CAVI) reflects the arterial stiffness of the arterial tree from the origin of the aorta to the ankle independent from BP during measurement. Additionally, CAVI reflects functional stiffness in addition to structural stiffness. We aimed to clarify the role of CAVI in regulating the BP system during HD. We included 10 patients undergoing 4-hour HD (total 57 HD sessions). Changes in the CAVI and various hemodynamic parameters were evaluated during each session. During HD, BP decreased and CAVI significantly increased (CAVI, median [interquartile range]; 9.1 [8.4–9.8] [0 min] to 9.6 [9.2–10.2] [240 min], p < 0.05). Changes in CAVI from 0 min to 240 min were significantly correlated with water removal rate (WRR) (r = −0.42, p = 0.002). Changes in CAVI at each measurement point were negatively correlated with ΔBP (Δsystolic BPeach MP, r = −0.23, p < 0.0001; Δdiastolic BPeach MP, r = −0.12, p = 0.029). Whereas one patient exhibited a simultaneous decrease in BP and CAVI during the initial 60 min of HD. Arterial stiffness monitored with CAVI generally increased during HD. CAVI elevation is associated with decreased WWR and BP. An increase in CAVI during HD may reflect the contraction of smooth muscle cells and play an important role in BP maintenance. Hence, measuring CAVI during HD may distinguish the cause of BP changes.

Background: Screening-based intrapartum antibiotic prophylaxis (IAP) has reduced the prevalence of early-onset group B Streptococcus (GBS) infection in newborns. Nevertheless, early-onset disease still occurs despite IAP, and IAP is not effective in preventing late-onset disease. This study aimed to determine the prevalence and risk factors of GBS neonatal umbilical colonization managed by dry cord care in Japan. Methods: Of 735 healthy newborns in the well-baby nursery at Saitama City Hospital, 353 from whom umbilical bacterial swabs were obtained before discharge were included in the analysis. Maternal and neonatal clinical characteristics were retrospectively reviewed. Results: GBS was detected in 4.2% (15/353) of umbilical swabs; 13/15 (86.8%) were born to GBS-negative mothers. The median (IQR) age at umbilical swab collection was 4.0 (4.0–5.0) days. Comparison of clinical characteristics between GBS-positive and negative neonates revealed a significant difference in the proportion of vaginal deliveries (15/15 [100%] in GBS-positive neonates vs. 115/338 [34.0%] in GBS-negative neonates, p

Abstract Frameshifts in the Calreticulin (CALR) exon 9 provide a recurrent driver mutation of essential thrombocythemia (ET) and primary myelofibrosis among myeloproliferative neoplasms (MPNs). Here, we generated knock-in mice with murine Calr exon 9 mimicking the human CALR mutations, using the CRISPR-Cas9 method. Knock-in mice with del10 [Calr del10/WT (wild−type) mice] exhibited an ET phenotype with increases of peripheral blood (PB) platelets and leukocytes, and accumulation of megakaryocytes in bone marrow (BM), while those with ins2 (Calr ins2/WT mice) showed a slight splenic enlargement. Phosphorylated STAT3 (pSTAT3) was upregulated in BM cells of both knock-in mice. In BM transplantation (BMT) recipients from Calr del10/WT mice, although PB cell counts were not different from those in BMT recipients from Calr WT/WT mice, Calr del10/WT BM-derived macrophages exhibited elevations of pSTAT3 and Endothelin-1 levels. Strikingly, BMT recipients from Calr del10/WT mice developed more severe pulmonary hypertension (PH)—which often arises as a comorbidity in patients with MPNs—than BMT recipients from Calr WT/WT mice, with pulmonary arterial remodeling accompanied by an accumulation of donor-derived macrophages in response to chronic hypoxia. In conclusion, our murine model with the frameshifted murine Calr presented an ET phenotype analogous to human MPNs in molecular mechanisms and cardiovascular complications such as PH.

Abstract Background While hand and ultrasonic scalers are the primary tools used for the removal of dental calculus in periodontal treatment, many studies have shown that they also damage the enamel surface. We have developed a novel actuator-driven pulsed water jet (ADPJ) system, which has the ability to selectively remove materials depending on their stiffness. Considering the different material properties between teeth and dental calculus, it might be possible to develop the ADPJ to remove dental calculus without damage to the tooth’s enamel surface using a suitable jet pressure. Therefore, the aim of this study was to assess the effectiveness of the ADPJ in removing dental calculus, and the surface features of the teeth after its use. Methods A total of 93 artificial teeth coated with artificial dental calculus were examined in this study. The weights of 90 teeth were measured before and after the use of ADPJ, which had an applied voltage setting of 150, 200, or 240 V. The three remaining teeth were instrumented with a conventional hand scaler, ultrasonic scaler, or ADPJ (set at 240 V). Damage to the artificial tooth surfaces was evaluated using 5% Evans blue dye under an optical microscope. Furthermore, apatite pellets, which are utilized as experimental substitutes for natural teeth, were assessed after the use of ADPJ and both conventional scalers. Results The ADPJ significantly reduced the amount of artificial calculus, and the removal rate was dependent on the applied voltage. No damage was observed on the surface of the artificial tooth and apatite pellet following the use of ADPJ, in contrast to the conventional scalers. Conclusions The results of this study demonstrate the in vitro effectiveness of ADPJ in the removal of dental calculus, without causing damage to tooth surfaces.

Monocarboxylates, such as lactate and pyruvate, are precursors for biosynthetic pathways, including those for glucose, lipids, and amino acids via the tricarboxylic acid (TCA) cycle and adjacent metabolic networks. The transportation of monocarboxylates across the cellular membrane is performed primarily by monocarboxylate transporters (MCTs), the membrane localization and stabilization of which are facilitated by the transmembrane protein basigin (BSG). Here, we demonstrate that the MCT/BSG axis sits at a crucial intersection of cellular metabolism. Abolishment of MCT1 in the plasma membrane was achieved by Bsg depletion, which led to gluconeogenesis impairment via preventing the influx of lactate and pyruvate into the cell, consequently suppressing the TCA cycle. This net anaplerosis suppression was compensated in part by the increased utilization of glycogenic amino acids (e.g., alanine and glutamine) into the TCA cycle and by activated ketogenesis through fatty acid β-oxidation. Complementary to these observations, hyperglycemia and hepatic steatosis induced by a high-fat diet were ameliorated in Bsg-deficient mice. Furthermore, Bsg deficiency significantly improved insulin resistance induced by a high-fat diet. Taken together, the plasma membrane–selective modulation of lactate and pyruvate transport through BSG inhibition could potentiate metabolic flexibility to treat metabolic diseases.

Abstract Background Besides research on psychiatric diseases related to problematic Internet use (PIU), a growing number of studies focus on the impact of Internet on subjective well-being (SWB). However, in previous studies on the relationship between PIU and SWB, there is little data for Japanese people specifically, and there is a lack of consideration for differences in perception of happiness due to cultural differences. Therefore, we aimed to clarify how happiness is interdependent on PIU measures, with a focus on how the concept of happiness is interpreted among Japanese people, and specifically among Japanese university students. Methods A paper-based survey was conducted with 1258 Japanese university students. Respondents were asked to fill out self-report scales regarding their happiness using the Interdependent Happiness Scale (IHS). The relationship between IHS and Internet use (Japanese version of the Internet addiction test, JIAT), use of social networking services, as well as social function and sleep quality (Pittsburgh Sleep Quality Index, PSQI) were sought using multiple regression analyses. Results Based on multiple regression analyses, the following factors related positively to IHS: female gender and the number of Twitter followers. Conversely, the following factors related negatively to IHS: poor sleep, high- PIU, and the number of times the subject skipped a whole day of school. Conclusions It was shown that there was a significant negative correlation between Japanese youths’ happiness and PIU. Since epidemiological research on happiness that reflects the cultural background is still scarce, we believe future studies shall accumulate similar evidence in this regard.

We are currently short of methods that can extract objective parameters of dendritic spines useful for their categorization. Authors present in this study an automatic analytical pipeline for spine geometry using 3D-structured illumination microscopy, which can effectively extract many geometrical parameters of dendritic spines without bias and automatically categorize spine population based on their morphological features

Abstract Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has recently become a challenging problem worldwide and in Japan. We experienced 10 pediatric patients infected with CA-MRSA and hospitalized from 2011 to 2014 in a tertiary care hospital in Saitama, Japan, and assessed the characteristic of the strains using a whole genome sequencing (WGS)-based approach. Methods CA-MRSA strains isolated from infected patients who required hospitalization for treatment were evaluated in this study. Antimicrobial susceptibility tests, molecular typing by PCR and pulse-field gel electrophoresis (PFGE) were performed to characterize MRSA strains. WGS was performed for detailed genetic analysis. Results A total of 582 MRSA strains (35.2%) were identified among 1625 S. aureus strains collected during the study period. Ten MRSA strains (1.7%) were defined as CA-MRSA clinically, and all were isolated from pediatric patients. All strains mainly caused purulent lymphadenitis, were susceptible to fluoroquinolone and tetracycline, exhibited sequence type (ST) 834 or its single-locus variants and contained staphylococcal cassette chromosome mec (SCCmec) type IVc. Phylogenic analysis by PFGE and WGS revealed close relatedness of all strains, with the number of single nucleotide polymorphisms ranging from 35 to 119 by WGS. Out of the ten strains, nine possessed the genomic island SaPISaitama2 containing tst, sec and sel genes. SaPISaitama2 comprises a mosaic of genomic islands SaPIm4 and SaPIm1 harbored by a hospital-associated MRSA strain Mu50. Conclusions This study describes a regional outbreak of ST834-related CA-MRSA in children with a unique pathogenicity island in Japan. Pediatric patient tropism of this clone could be enhanced by susceptibility to fluoroquinolones and tetracyclines, which cannot be prescribed to children.

Newly synthesized naphthalene diimide carrying two β-cyclodextrins (NDI-β-CyDs) showed improved specificity for the parallel G-quadruplex structure alongside the hybrid G-quadruplex structure. Specifically, the highest binding affinity of NDI-β-CyDs for the telomere RNA G-quadruplex was observed. The binding simulation indicated that β-cyclodextrins might be available for loop nucleobase inclusion under its complex.

Abstract Background Fructose intake, mainly as table sugar or high fructose corn syrup, has increased in recent decades and is associated with increased risk for kidney stones. We hypothesized that fructose intake alters serum and urinary components involved in stone formation. Methods We analyzed a previously published randomized controlled study that included 33 healthy male adults (40–65 years of age) who ingested 200 g of fructose (supplied in a 2-L volume of 10% fructose in water) daily for 2 weeks. Participants were evaluated at the Unit of Nephrology of the Mateo Orfila Hospital in Menorca. Changes in serum levels of magnesium, calcium, uric acid, phosphorus, vitamin D, and intact PTH levels were evaluated. Urine magnesium, calcium, uric acid, phosphorus, citrate, oxalate, sodium, potassium, as well as urinary pH, were measured. Results Ingestion of fructose was associated with an increased serum level of uric acid (p

Abstract Background Increasing evidence suggests heat stress induced chronic kidney disease (CKD) may be mediated by endogenous fructose generation and may be exacerbated by rehydration by fructose-containing solutions. We have recently reported a model of CKD induced by heat stress. Here we test the hypothesis that rehydration with fructose may induce worse kidney injury than rehydration with equal amounts of water, and we also test if this fructose-induced injury is associated with activation of inflammasomes in the kidney. Methods Mice were recurrently exposed to heat (39.5 C0 for 30 min/h, 5 times daily for 5 wks) with rehydration consisting of 6 ml each night of water (Heat, n = 7) or fructose (Heat+F, 10%, n = 7), and were compared to control mice on water (Control, n = 7) or fructose (Fructose, n = 7). Various markers of renal injury were assessed. Results Compared to control animals, there was a progressive worsening of renal injury (inflammation and fibrosis) with fructose alone, heat stress alone, and heat stress with fructose rehydration (P

Objective: We aimed to evaluate the outcomes of growth-restricted fetuses with absent end-diastolic velocity in the umbilical arteries (UA-AEDV), and investigate the relationship between Doppler flow velocity waveforms in the ductus venosus (DV) and the clinical features. Materials and methods: This was a retrospective study of growth-restricted fetuses diagnosed with UA-AEDV delivered at our institution between 2013 and 2015. The time from diagnosis of UA-AEDV to delivery, postnatal survival, and developmental prognoses were the primary outcomes. The time lag between the occurrence of UA-AEDV and an abnormal increase in the DV pulsatility index (DV-PI) were investigated. We also examined the correlation between the DV-PI values immediately before birth and umbilical cord arterial pH at birth. Results: The median gestational age at birth among the 18 subjects was 28+2 (24+0–34+6) weeks, and the observation period between the first detection of UA-AEDV and delivery ranged from 0 to 35 days with a median of 8 days. Among the 18 infants, 15 (83%) survived, among whom 2 were diagnosed with a developmental disability. Gestational age at delivery was significantly lower in the poor outcome group. A positive correlation (correlation coefficient, 0.68) was observed between the umbilical artery pH and the last measured DV-PI. Conclusion: The time interval from initial detection of UA-AEDV to delivery is highly variable, and it is reasonable to manage these growth-restricted fetuses with UA-AEDV expectantly with careful surveillance for fetal well-being. Specifically, Doppler DV analysis is clinically valuable for their evaluation.

Highly active anti-retrovirus therapy (HAART) has been used to block the progression and symptoms of human immunodeficiency virus infection. Although it decreases morbidity and mortality, clinical use of HAART has also been linked to various adverse effects such as severe cardiomyopathy resulting from compromised mitochondrial functioning. However, the mechanistic basis for these effects remains unclear. Here, we demonstrate that a key component of HAART, 3ꞌ-azido-3ꞌ-deoxythymidine (AZT), particularly, its active metabolite AZT-triphosphate (AZT-TP), caused mitochondrial dysfunction, leading to induction of cell death in H9c2 cells derived from rat embryonic myoblasts, which serve as a model for cardiomyopathy. Specifically, treatment with 100 µM AZT for 48 h disrupted the mitochondrial tubular network via accumulation of AZT-TP. The mRNA expression of dynamin-related protein (Drp)1 and the Drp1 receptor mitochondrial fission factor (Mff) was upregulated whereas that of optic atrophy 1 (Opa1) was downregulated following AZT treatment. Increased mitochondrial translocation of Drp1, Mff upregulation, and decreased functional Opa1 expression induced by AZT impaired the balance of mitochondrial fission vs. fusion. These data demonstrate that AZT-TP causes cell death by altering mitochondrial dynamics.

Introduction. Although nonabsorbable woven tape has been widely used for cervical cerclage, technical difficulties that can occur with an effaced cervix because of the thickness of the tape, and the risks of local infection are two major concerns. This study investigated perinatal outcomes of pregnancies involving an emergency cervical cerclage using absorbable monofilament polydioxanone sutures, which is a narrow thread and protects against bacterial infection. Materials and Methods. We performed a chart review of patients who underwent emergency McDonald cerclage with polydioxanone sutures at our institution between 2007 and 2015. Gestational age at delivery, duration between cerclage and delivery, and neonatal prognosis were evaluated as primary outcomes. Results. Among the 23 patients (18 singleton and five twin pregnancies) evaluated, ultrasound-indicated (progressive cervical length shortening) were eight (35%) and physical examination-indicated (fetal membranes that prolapsed into the vagina or dilated cervix) were 15 patients (65%). The median gestational age at cerclage was 22+3 weeks (range, 17+5 to 25+3 weeks). Postoperative spontaneous abortion occurred in only one patient. The median gestational age at delivery was 32+5 weeks (range, 20+5 to 40+6 weeks). Extremely preterm delivery before 28 weeks of gestation occurred in four (17%) cases. Full-term delivery was achieved in 10 (42%) cases. The duration between cerclage and delivery ranged from 5 to 136 days (median, 77 days). Except for one case of spontaneous abortion, all newborns survived till hospital discharge. Conclusions. Although our series included some patients at high risk for spontaneous abortion and preterm delivery, satisfactory prolongation and favorable neonatal outcomes were achieved for most patients by using absorbable monofilament sutures, thus suggesting the efficacy of this type of suture for emergency cervical cerclage.

Sirenomelia is a rare congenital malformation characterized by varying degrees of fusion of the lower extremities. It is commonly associated with severe urogenital and gastrointestinal malformations; however, the association of sirenomelia with anencephaly and rachischisis totalis is extremely rare. To our knowledge, the prenatal sonographic images of this association have not been previously published. Here, we present prenatal sonographic images of this association, detected during the 17th week of gestation through combined two-dimensional, four-dimensional, and color Doppler ultrasound. Two-dimensional ultrasound images showed anencephaly, spina bifida, and possible fusion of the lower limbs. Three-dimensional HDlive rendering images confirmed the final diagnosis of sirenomelia with anencephaly and rachischisis totalis. The patient opted to undergo medical termination of pregnancy and delivered a fetus with fused lower limbs, anencephaly, and rachischisis totalis confirming the in utero imaging findings. Awareness of these rare associations will help avoid misdiagnoses and facilitate prenatal counselling. This case highlights the importance of a thorough ultrasound examination.

Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

Abstract: A 68-year-old man was admitted because of tonic–clonic convulsion. He had been receiving 200 mg itraconazole for 10 days. He had hypokalaemia (2.2 mEq/l), hypercalcaemia (Cacorr 11.0 mg/dl) and elevated serum parathyroid hormone (PTH, 95 pg/ml). Ultrasound examination of the neck revealed a low echoic tumour. Cessation of itraconazole and fluid supplementation eradicated clinical symptoms and profound hypokalaemia, but serum potassium remained low normal (3.4 mEq/l) and the mild hypercalcaemia and elevated PTH were unchanged. To conclude, a small amount of itraconazole (200 mg) precipitated profound hypokalaemia and seizure in a patient with mild hyperparathyroidism and low normal serum potassium.

The treatment of laryngotracheal stenosis remains a challenge as treatment often requires multistaged procedures, and successful decannulation sometimes fails after a series of operations. Induced pluripotent stem cells (iPSCs) were generated in 2006. These cells are capable of unlimited symmetrical self-renewal, thus providing an unlimited cell source for tissue-engineering applications. We have previously reported tracheal wall regeneration using a three-dimensional (3D) scaffold containing iPSCs. However, the efficiency of differentiation into cartilage was low. In addition, it could not be proven that the cartilage tissues were in fact derived from the implanted iPSCs. The purpose of this study was to evaluate and improve the use of iPSCs for the regeneration of tracheal cartilage. iPSCs were cultured in vitro in a 3D scaffold in chondrocyte differentiation medium. After cultivation, differentiation into chondrocytes was examined. The ratio of undifferentiated cells was analyzed by flow cytometry. The 3D scaffolds were implanted into tracheal defects, as an injury site, in 24 nude rats. Differentiation into chondrocytes in vitro was confirmed histologically, phenotypically, and genetically. Flow cytometric analysis demonstrated that the population of undifferentiated cells was decreased. Cartilage tissue was observed in the regenerated tracheal wall in 6 of 11 rats implanted with induced iPSCs, but in none of 13 rats implanted with the control and noninduced iPSCs. The expression of cartilage-specific protein was also demonstrated in vivo in 3D scaffolds containing iPSCs. The presence of the GFP gene derived from iPSCs was confirmed in samples of cartilage tissue by the combination of laser microdissection (LMD) and polymerase chain reaction (PCR) techniques. Our study demonstrated that iPSCs have the potential to differentiate into chondrogenic cells in vitro. Cartilage tissue was regenerated in vivo. Our results suggest that iPSCs could be a new cell source for the regeneration of tracheal cartilage.

Current research highlights the need for more studies focused on how high-quality assessment strategies can contribute to coach learning in coach education. The use of e-portfolios, as formative assessment tools, has shown to contribute to student-coaches' learning in university-based programs, but studies on this topic are still scarce. The aim of this action research project is to investigate the potentialities and challenges of the e-portfolio as a formative learning-oriented assessment tool in an undergraduate sport coach course in Brazil. By sharing this, from the perspective of student-coaches and the assistant-professors of the course, we reflect on the evidence with the intention to both inform colleagues doing similar work and contribute to an emerging body of assessment in coach education literature. [ABSTRACT FROM AUTHOR]