Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3-year follow-up of multicenter trial.

OBJECTIVES: Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia. METHODS: This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed. RESULTS: Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1-9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI. CONCLUSIONS: This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Utility of synthetic MRI in predicting pathological complete response of various breast cancer subtypes prior to neoadjuvant chemotherapy.

AIM: To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a pathological complete response (pCR) after the completion of NAC. MATERIALS AND METHODS: This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density [PD] and their standard deviations [SD]) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR. RESULTS: Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively. CONCLUSIONS: The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies.

Evaluation of flexible ureteroscope with an omni-directional bending tip, using a JOYSTICK unit (URF-Y0016): an ex-vivo study.

PURPOSE: To compare the range of reach of our newly designed omni-directional ureteroscope (URF-Y0016), compared to the commonly used URF-P6, FlexX2s, and LithoVue™ scopes, in the upper, middle, and lower calyces in an ex-vivo pyelocaliceal model. METHODS: We fabricated a three-dimensional pyelocaliceal model of the upper, middle, and lower pole calyces using urethane and acrylic resin. The inner surface of the dome of each calyx was engraved with reference lines along eight directions, set at 10° of latitude from the top to the base of the dome, and at angles of 0-90°, to precisely determine the range of reach of each scope. The main feature of the URF-Y0016 scope is the omni-directional bending of the tip of the flexible ureteroscope, with the control of these four directions integrated into a handgun-type control unit with a joystick. The range of reach within each calyx was measured by four expert surgeons. RESULTS: The URF-Y0016 scope provided a greater range of reach along all directions in the lower pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p < 0.001), particularly along the anterior-posterior direction in the lower lobe calyx. However, the URF-Y0016 scope did not influence the improvement of reach range in the upper and middle pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p = 0.08, p = 0.296). CONCLUSION: The novel design of the URF-Y0016 could improve treatment outcomes for calyceal stones in the lower pole in practice.

Safety and feasibility of minimally invasive esophagectomy for elderly esophageal cancer patients.

The number of elderly patients with esophageal cancer has increased in recent years. The use of thoracoscopic esophagectomy has also increased, and its minimal invasiveness is believed to contribute to postoperative outcomes. However, the short- and long-term outcomes in elderly patients remain unclear. This study aimed to elucidate the safety and feasibility of minimally invasive esophagectomy in elderly patients. This retrospective study included 207 patients who underwent radical thoracoscopic esophagectomy for thoracic esophageal squamous cell carcinoma at Kobe University Hospital between 2005 and 2014. Patients were divided into non-elderly (<75 years) and elderly (≥75 years) groups. A propensity score matching analysis was performed for sex and clinical T and N stage, with a total of 29 matched pairs. General preoperative data, surgical procedures, intraoperative data, postoperative complications, in-hospital death, cancer-specific survival, and overall survival were compared between groups. The elderly group was characterized by lower preoperative serum albumin levels and higher American Society of Anesthesiologists grade. Intraoperative data and postoperative complications did not differ between the groups. The in-hospital death rate was 4% in the elderly group, which did not significantly differ from the non-elderly group. Cancer-specific survival was similar between the two groups. Although overall survival tended to be poor in the elderly group, it was not significantly worse than that of the non-elderly group. In conclusion, the short- and long-term outcomes of minimally invasive esophagectomy in elderly versus non-elderly patients were acceptable. Minimally invasive esophagectomy is a safe and feasible modality for elderly patients with appropriate indications.

A randomized, open-label, controlled trial of monthly oral minodronate or semiannual subcutaneous injection of denosumab for bone loss by androgen deprivation in Asian men with prostate cancer: the PRevention of Osteopenia with Minodronate And DEnosumab (PROMADE) study.

There is still a lack of evidence that minodronate or denosumab prevents bone loss due to androgen deprivation therapy (ADT) in non-Western patients. This study showed that both drugs significantly improved lumbar spine and total hip bone mineral density in Asian men with prostate cancer who received ADT. INTRODUCTION: To evaluate whether monthly oral minodronate or semiannual subcutaneous injection of denosumab improves bone mineral density (BMD) in Asian men with prostate cancer (PCa) receiving ADT. METHODS: A multicenter, open-label, randomized, controlled study including patients with hormone-sensitive PCa without bone metastasis receiving ADT was performed. Patients were randomized (1:1:1) to minodronate, denosumab, or no agent control groups. The primary end point was the mean percentage change in BMD at the lumbar spine at 12 months. Secondary end points were the mean percentage change in BMD at the femoral neck and total hip and changes in bone turnover markers. Statistical comparison was performed using analysis of covariance. RESULTS: Of the 147 subjects enrolled in this study, 102 were randomly assigned into the minodronate (n = 36), denosumab (n = 36), and control (n = 30) groups. The percentage change in BMD at the lumbar spine was significantly improved in the minodronate (2.5%, p < 0.05) and denosumab groups (4.0%, p < 0.01) compared with that in the control group (- 0.1%). Denosumab increased BMD at the femoral neck and total hip at 12 months, whereas minodronate only increased BMD at the total hip compared with controls (all p < 0.05). The percentage change in bone turnover markers at 12 months was significantly lower in the minodronate and denosumab groups compared with that in the control group (both p < 0.01). CONCLUSION: Minodronate or denosumab can be used for preventing bone loss related to ADT in Asian patients with PCa.

Evidence for Spin Singlet Pairing with Strong Uniaxial Anisotropy in URu_{2}Si_{2} Using Nuclear Magnetic Resonance.

In order to identify the spin contribution to superconducting pairing compatible with the so-called "hidden order", ^{29}Si nuclear magnetic resonance measurements have been performed using a high-quality single crystal of URu_{2}Si_{2}. A clear reduction of the ^{29}Si Knight shift in the superconducting state has been observed under a magnetic field applied along the crystalline c axis, corresponding to the magnetic easy axis. These results provide direct evidence for the formation of spin-singlet Cooper pairs. Consequently, results indicating a very tiny change of the in-plane Knight shift reported previously demonstrate extreme uniaxial anisotropy for the spin susceptibility in the hidden order state.

Pathotyping of Escherichia coli isolated from community toilet wastewater and stored drinking water in a slum in Bangladesh.

This study investigated the occurrence of Escherichia coli pathotypes in sanitary wastewater and drinking water in a Bangladeshi urban slum and the potential associations between these sources. We examined 621 E. coli isolates from sanitary wastewater and stored drinking water by multiplex PCR and dual-index sequencing, classifying them into eight pathotypes based on 14 virulence genes and additionally evaluating the possession of the human-specific E. coli genetic biomarker H8. The proportions of pathogenic E. coli were significantly different (P < 0·001) between wastewater (18·6%) and drinking water (1·7%). StIb-positive enterotoxigenic E. coli (ETEC) were predominant in wastewater, indicating that people in the site carried ETEC. In contrast, no ETEC was present in drinking water and the proportion of H8-positive isolates was significantly smaller (7·8%) than that in wastewater (16·3%) (P = 0·001). Our findings indicate that sanitary wastewater from the slum was heavily contaminated with pathogenic E. coli, posing a great health risk. Furthermore, E. coli contamination of drinking water could be derived from not only human but also other sources. SIGNIFICANCE AND IMPACT OF THE STUDY: Sanitary wastewater from an urban slum was heavily contaminated with pathogenic Escherichia coli. It is worth noting a great health risk of accidental exposure to pathogenically contaminated wastewater improperly discharged in and around urban slums. The distinct difference in pathotypes between wastewater and drinking water and the significantly smaller positive proportion of the human-specific E. coli genetic biomarker (H8) in drinking water indicate that drinking water contamination could be derived from not only human but also other sources. This highlights that pathotyping in association with the H8 marker provides an indication of pathogen contamination sources of environmental transmission media.

C-reactive protein to albumin ratio is a prognostic factor for patients with cStage II/III esophageal squamous cell cancer.

C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, was first developed as a prognostic score for septic patients. Recent reports show that CRP/Alb ratio is also a prognostic score for cancer patients, including esophageal cancer. However, the role of CRP/Alb ratio for those with neoadjuvant chemotherapy (NAC) and the changes of CRP/Alb ratio around NAC have never been discussed. The aim of this study is to evaluate the significance of CRP/Alb ratio around NAC for patients with cStage II/III esophageal squamous cell cancer (ESCC). A total of 149 patients who were diagnosed as cStage II/III ESCC were enrolled between February 2007 and December 2014. We retrospectively investigated the relation between pre-NAC and post-NAC CRP/Alb ratio and short and long outcomes. The optimal cutoff level for pre-NAC and post-NAC CRP/Alb ratio was 0.030 and 0.048, respectively. There was no relation between CRP/Alb ratio level and postoperative outcomes. Post-NAC CRP/Alb ratio < 0.048 had a significantly higher overall survival rate than CRP/Alb ratio ≥0.048 (P< 0.001). Univariate analysis showed that cT, cN, pre-NAC CRP/Alb ratio < 0.030 and post-NAC CRP/Alb ratio < 0.048 was prognostic factors (P= 0.003, P= 0.022, P= 0.033, and P< 0.001, respectively). Multivariate analysis showed that cT and post-NAC CRP/Alb ratio < 0.048 was independent prognostic factors (P= 0.030 and P< 0.001, respectively). Post-NAC CRP/Alb ratio is an independent prognostic factor in patients with cStage II/III ESCC.

Expression of hOvol2 in the XY body of human spermatocytes.

Male infertility is common at infertile clinics, and 10-20% of infertile males are azoospermic. Non-obstructive azoospermia is a complex multifactorial disease, and the process of spermatogenesis remains largely unknown. Ovol1 and Ovol2, a family of zinc finger transcription factors, are expressed in spermatocytes at the pachytene stage and are suggested to be critical regulators of pachytene progression in male germ cells. In this study, we examined the expression of human Ovol2 (hOvol2) in the seminiferous tubes of patients subjected to testicular sperm extraction. We first cloned hOvol1 and hOvol2 from the testis of one of the patients and found no alteration in these nucleotide sequences of this patient. While hOvol1 and hOvol2 were detected by RT-PCR in the testis of patients capable of spermatogenesis, they were not detected in those with Sertoli cell-only syndrome. We recently succeeded in preparing anti-Ovol2 antibody by immunising rats with recombinant mouse Ovol2 (mOvol2) and confirmed the specificity and cross-reactivity of this antibody with hOvol2 in cells transfected with hOvol1 or hOvol2 cDNA. hOvol2 expression was restricted to the XY body of spermatocytes at the pachytene stage. This study demonstrates that hOvol2 is expressed in germ cells and may be involved in spermatogenesis.

Relationship between volume of the seminal vesicles and sexual activity in middle-aged men.

The relationship between volume of the seminal vesicles and the frequency of sex and sexual function in middle-aged men is not clear. This study included 81 patients who were diagnosed with localized prostate cancer. Volume of the seminal vesicles was examined using a volume analyser from computed tomography. Sexual function was subjectively evaluated using the Expanded Prostate Cancer Index Composite and Erection Hardness Score. The frequency of sex was surveyed using our original questionnaire. The mean ± SD age of the patients was 67.7 ± 5.3 years. There was no relationship between the volume of seminal vesicles and age of the patients. Volume of the seminal vesicles in patients who answered that they had sexual activity at least once a year was significantly larger than in those who answered no sexual activity for several years (P < .01) Moreover, among sexually active, middle-aged men, volume of the seminal vesicles was significantly larger in those who had a sexual frequency once every 3 months than in those who had a sexual frequency once every 6 months or once a year (P < .05). Our study suggests that the volume of seminal vesicles of middle-aged men is correlated with sexual activity.

Spontaneous Polarization and Bulk Photovoltaic Effect Driven by Polar Discontinuity in LaFeO_{3}/SrTiO_{3} Heterojunctions.

Structurally coherent and chemically abrupt interfaces formed between polar and nonpolar perovskite oxides provide an ideal platform for examining the purely electronic reconstruction known as the polar catastrophe and the emergence of mobile or bound charges at the interface. The appearance of mobile charges induced by the polar catastrophe is already established in the LaAlO_{3}/SrTiO_{3} heterojunctions. Although not experimentally verified, the polar catastrophe can also lead to the emergence of spontaneous polarization. We report that thin films of originally nonpolar LaFeO_{3} grown on SrTiO_{3} are converted to polar as a consequence of the polar catastrophe. The induced spontaneous polarization evokes photovoltaic properties distinct from conventional p-n junctions, such as a switching of the photocurrent direction by changing the interfacial atomic sequence. The control of the bulk polarization by engineering the interface demonstrated here will expand the possibilities for designing and realizing new polar materials with photovoltaic functions.

Interference Effect between ϕ and Λ(1520) Production Channels in the γp→K

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

OBJECTIVE: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. DESIGN: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. RESULTS: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. CONCLUSIONS: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

Thermal Conductivity through the Quantum Critical Point in YbRh_{2}Si_{2} at Very Low Temperature.

The thermal conductivity of YbRh_{2}Si_{2} has been measured down to very low temperatures under field in the basal plane. An additional channel for heat transport appears below 30 mK, both in the antiferromagnetic and paramagnetic states, respectively, below and above the critical field suppressing the magnetic order. This excludes antiferromagnetic magnons as the origin of this additional contribution to thermal conductivity. Moreover, this low temperature contribution prevails a definite conclusion on the validity or violation of the Wiedemann-Franz law at the field-induced quantum critical point.

Observation of a Devil's Staircase in the Novel Spin-Valve System SrCo6O11.

Using resonant soft-x-ray scattering as a function of both temperature and magnetic field, we reveal a large number of almost degenerate magnetic orders in SrCo6O11. The Ising-like spins in this frustrated material in fact exhibit a so-called magnetic devil's staircase. It is demonstrated how a magnetic field induces transitions between different microscopic spin configurations, which is responsible for the magnetoresistance of SrCo6O11. This material therefore constitutes a unique combination of a magnetic devil's staircase and spin-valve effects, yielding a novel type of magnetoresistance system.

Common otolith microstructure related to key early life-history events in flatfishes identified in the larvae and juveniles of cresthead flounder Pseudopleuronectes schrenki.

Otolith microstructure of reared and wild cresthead flounder Pseudopleuronectes schrenki larvae and juveniles was used to investigate the daily periodicity of ring formation, morphological change and unique otolith structure related to important life events. By comparing microstructural features of P. schrenki with those reported for other flatfish species, it was shown that there may be microstructural features that are common to all flatfishes. In the sagittae and lapillus, a check (a distinct ring) was formed in the centre of otoliths at c. 6 days post hatching, and the daily formation of rings observed outside the check was confirmed. During metamorphosis, accessory primordia (AP) of otolith growth were formed on the outer edge of the sagittae, and the shape of the sagittae became more complex. No AP was formed on the lapilli, however, and otolith rings were concentrically formed throughout the larval and juvenile (≤51·6 mm standard length, LS ) stages. It is proposed, therefore, that lapilli are more appropriate than sagittae for analysis throughout the larval and juvenile (≤51·6 mm LS ) stages. During metamorphosis, unique rings that are relatively wide and show weak contrast are formed on lapilli (metamorphosing zone, MZ). Hence, the duration of metamorphosis, larval duration and the days of juvenile life can be estimated by the number of rings within the MZ, using rings from the check to outermost ring of the MZ, and that of rings formed outside MZ, respectively. The formation of AP on sagittae as well as the absence of AP, bilateral asymmetry and the formation of a unique structure during metamorphosis on lapilli have also been reported for other flatfishes.

Histological and molecular characterization of the femoral attachment of the human ligamentum capitis femoris.

The ligamentum capitis femoris (LCF) has increased in clinical significance through the development of hip arthroscopy. The histological pathologies and molecular composition of the femoral attachment of the LCF and the degeneration caused by LCF disruption were investigated in the human hip joint. Twenty-four LCFs were retrieved at surgery for femoral neck fracture (age range: 63-87 years). In the "intact" (i.e., intact throughout its length, n = 12) group, the attachment consisted of rich fibrocartilage. Fibrocartilage cells were present in the midsubstance. In contrast, the construction of the attachment in the "disrupted" (i.e., ligament no longer attached to the femoral head, n = 12) group had disappeared. The attachment in the disrupted group was not labeled for type II collagen or aggrecan, while that in the intact group was labeled for types I, II and III collagen, chondroitin 4-sulfate, chondroitin 6-sulfate, aggrecan, and versican. The percentage of single-stranded DNA-positive chondrocytes was significantly higher in the disrupted group than in the intact group. We conclude that the femoral attachment of the LCF has a characteristic fibrocartilaginous structure that is likely to adjust to the mechanical load, and suggest that its degeneration is advanced by disruption and should be regarded as a clinical pathology.