Embryonic statistical analyses reveal 2 growth phenotypes in mouse models of Down syndrome.

BACKGROUND: Down syndrome is associated with several comorbidities, including intellectual disability, growth restriction, and congenital heart defects. The prevalence of Down syndrome-associated comorbidities is highly variable, and intellectual disability, although fully penetrant, ranges from mild to severe. Understanding the basis of this interindividual variability might identify predictive biomarkers of in utero and postnatal outcomes that could be used as endpoints to test the efficacy of future therapeutic interventions. OBJECTIVE: The main objective of this study was to examine if antenatal interindividual variability exists in mouse models of Down syndrome and whether applying statistical approaches to clinically relevant measurements (ie, the weights of the embryo, placenta, and brain) could define cutoffs that discriminate between subgroups of trisomic embryos. STUDY DESIGN: Three commonly used mouse models of Down syndrome (Dp(16)1/Yey, Ts65Dn, and Ts1Cje) and a new model (Ts66Yah) were used in this study. Trisomic and euploid littermate embryos were used from each model with total numbers of 102 for Ts66Yah, 118 for Dp(16)1/Yey, 92 for Ts65Dn, and 126 for Ts1Cje. Placental, embryonic, and brain weights and volumes at embryonic day 18.5 were compared between genotypes in each model. K-mean clustering analysis was applied to embryonic and brain weights to identify severity classes in trisomic embryos, and brain and placental volumetric measurements were compared between genotypes and classes for each strain. In addition, Ts66Yah embryos were examined for malformations because embryonic phenotypes have never been examined in this model. RESULTS: Reduced body and brain weights were present in Ts66Yah, Dp(16)1/Yey, and Ts65Dn embyos. Cluster analysis identified 2 severity classes in trisomic embryos-mild and severe-in all 4 models that were distinguishable using a putative embryonic weight cutoff of <0.5 standard deviation below the mean. Ts66Yah trisomic embryos develop congenital anomalies that are also found in humans with Down syndrome, including congenital heart defects and renal pelvis dilation. CONCLUSION: Statistical approaches applied to clinically relevant measurements revealed 2 classes of phenotypic severity in trisomic mouse models of Down syndrome. Analysis of severely affected trisomic animals may facilitate the identification of biomarkers and endpoints that can be used to prenatally predict outcomes and the efficacy of treatments.

Conceptualizing and Measuring Social Media Use in Health and Well-being Studies: Systematic Review.

BACKGROUND: Despite an increasing number of studies revealing both the benefits and harms of social media use on well-being, there is heterogeneity and a lack of consensus on how social media use is conceptualized, defined, and measured. Additionally, little is known whether existing literature focuses on ill-being or well-being outcomes and whether studies use theories. OBJECTIVE: The main objective of this review was to examine (1) how social media use has been conceptualized and measured, (2) what health and well-being outcomes have been focused on, and (3) whether studies used theories. METHODS: Studies were located through a comprehensive search strategy involving 4 steps. First, keyword searches were conducted on 6 major databases: PubMed, Web of Science, PsycINFO, Embase, ProQuest, and Annual Reviews. Second, a search was conducted on Google Scholar using the same sets of search terms, and the first 100 results were examined. Third, the reference sections of reviews identified in the first 2 rounds of searches were examined, and finally, the reference lists of the final set of papers included in the review were searched. Through a multistage screening, papers that met our inclusion criteria were analyzed. RESULTS: The review included a total of 233 papers published between 2007 and 2020 in 51 different countries. While 66 (28%) of the studies investigated the effects of the problematic use or addiction of social media on health and well-being, 167 (72%) studied the effects of social media use as a "normal" behavior. Most of the studies used measures assessing the time users spend using social media. Most of the studies that examined the effects of problematic social media use or addiction used addiction scales. Most studies examined the association of social media use with mental illnesses such as depression, anxiety, self-esteem, and loneliness. While there are a considerable number of studies investigating physical health outcomes such as self-rated health, sleep, and sitting time or lack of physical activity, relatively a small number of studies examined social, psychological, and emotional well-being. Most of the studies 183 (79%) did not use any theory. CONCLUSIONS: Most studies conceptualized social media use as a "normal" behavior and mostly used time-spent measures, whereas a considerable number of studies conceptualized social media use as an addiction and used various addiction measures. The studies disproportionately focused on investigating the associations of social media use with negative health and well-being outcomes. The findings suggest the need for going beyond time spent to more sophisticated measurement approaches that consider the multiplicity of activities that users perform on social media platforms and the need for more theory-based studies on the association of social media use with not only negative well-being or "ill-being" but also with positive health and well-being outcomes.

Hip abduction angle after open-wedge high tibial osteotomy is associated with the timed up & go test and recurrence of varus alignment.

The aim of this study is to investigate the association between the hip abduction angle (HAA) and lower limb alignment as well as the clinical assessments in open-wedge high tibial osteotomy (OWHTO) patients. A total of 90 patients who underwent OWHTO were included. The demographic characteristics and clinical assessments (the Visual Analogue Scale for activities of daily living, the Japanese knee osteoarthritis measure, the Knee injury and Osteoarthritis Outcome Score, the Knee Society score, the Timed Up & Go (TUG) test, the single standing (SLS) test and muscle strength) were recorded. The patients were divided into two groups according to the HAA at 1 month after operation: the HAA (-) group (HAA < 0°) and the HAA (+) group (HAA ≥ 0°). Clinical scores except for the SLS test and radiographic parameters except for the posterior tibia slope (PTS), lateral distal femoral angle (LDFA) and lateral distal tibial angle (LDTA) were significantly improved at 2 years postoperatively. Regarding the two groups, scores on the TUG test in the HAA (-) group were significantly lower than those in the HAA (+) group (p = 0.011). The hip-knee-ankle angle (HKA), weight bearing line (WBLR) and knee joint line obliquity (KJLO) in the HAA (-) group were significantly higher than those in the HAA (+) group (p < 0.001, 0.001 and p = 0.025). In contrast, the LDFA in the HAA (-) group were significantly lower than those in the HAA (+) group (p < 0.001). The TUG test and the LDFA were weakly positively correlated with the HAA (r = 0.34, 0.42, p < 0.001 and 0.001). In contrast, the HKA, WBLR and KJLO had a weak negative correlation with the HAA (r = - 0.43, - 0.38 and - 0.37, p < 0.001, 0.001 and 0.001). This study showed the postoperative HAA was significantly associated with the TUG test and the HKA, WBLR, LDFA, and KJLO. A higher postoperative HAA might induce varus recurrence and poor outcomes of the gait parameter.

Novel missense COL2A1 variant in a fetus with achondrogenesis type II.

Achondrogenesis type II (ACG2) is a lethal skeletal disorder caused by pathogenic variants in COL2A1. We present a fetus with cystic hygroma and severe shortening of the limbs at 14 weeks of gestation. We performed postnatal genetic analysis of the parents and fetus to diagnose the disease. A novel missense variant of COL2A1 [NM_001844.5: c.2987G>A, (p. Gly996Asp)] was identified, which led to the ACG2 diagnosis.

Pregnancy Outcome and Postnatal Chromosome Analysis of the Cord Blood and Chorionic Villi in Two Cases after Intrauterine Transfer of Mosaic Aneuploid Blastocysts.

The long-term prognosis and genetic mechanism of pregnancy after intrauterine mosaic aneuploid blastocyst transfer remain unknown. We report the case of two babies after the aforementioned procedure and chromosomal analysis of their cord blood and chorionic villi. Case Report 1. A 41-year-old primipara, with two previous spontaneous abortions, was pregnant after intrauterine transfer of a blastocyst carrying 40% mosaicism of long-arm monosomy of chromosome 5. The amniocentesis results were 46,XX. A cesarean section was performed at 39 weeks. The female infant was 3,315 g at birth. Case Report 2. A 44-year-old primipara, with two spontaneous abortions, was pregnant after intrauterine transfer of a blastocyst carrying 40% mosaicism of long-arm monosomy of chromosome 9 and monosomy of chromosome 14. After genetic counselling, she decided not to undergo amniocentesis. No abnormalities were found by ultrasound. A cesarean section was performed at 38 weeks. The male infant was 3,340 g at birth. Chromosome analyses of postnatal cord blood and chorionic villi were performed using SNP arrays. The cord blood and chorionic villi showed no chromosomal structural abnormalities or mosaicism. For both, no disorders were observed at 10 months of age. We experienced the birth of babies after intrauterine transfer of mosaic aneuploid blastocysts.

Clinical outcomes in pregnant women with coronavirus disease 2019 in a perinatal medical centre in Japan: a retrospective study of the first 1 year of the pandemic.

In this retrospective study, we analysed clinical and demographic data from the medical records of 31 pregnant women with coronavirus disease 2019 (COVID-19) who were treated at our hospital between April 2020 and April 2021. The most common symptom was a fever; ∼10% of patients were asymptomatic. One patient with rapidly worsening pneumonia needed a Caesarean Section at 30 weeks and was admitted for intensive care. Twelve patients received perinatal care in our hospital (10 live births, one stillbirth, and one artificial abortion). Six patients delivered vaginally; the others delivered via caesarean section. Two patients had complications, including severe hypertensive disorders and preeclampsia. All patients recovered from COVID-19. Severe acute respiratory syndrome coronavirus 2 was not detected in the placenta, umbilical cord, cord blood, amniotic fluid, vaginal fluid, or breast milk in any patient. There were no neonatal adverse outcomes. The possibility of transmitting the coronavirus to pregnancy-related samples was low.IMPACT STATEMENTWhat is already known on the subject? COVID-19 has been affecting different countries in diverse ways, and the incidence, mortality, and morbidity rates of patients with COVID-19 vary widely by country or region and race. These differences in results may reflect racial differences and differences in national health care systems. Moreover, the information about the perinatal outcomes of pregnant women with COVID-19 and their newborns from Japan is limited.What do the results of this study add to what is known? We described the perinatal outcomes of 31 Japanese pregnant women with COVID-19 who were managed safely in a perinatal medical centre in Tokyo Japan, during the first 1 year of the pandemic.What are the implications of these findings for clinical practice and/or further research? Severe pneumonia and perinatal complications may occur, although no maternal and neonatal deaths were observed for COVID-19-positive pregnant women in our facility. Therefore, it is important to prevent this infection during pregnancy with the provision of effective medical care.

Perinatal management of a pregnant woman with COVID-19: A case report from Japan.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Owing to limited information, the impact and clinical course of COVID-19 in pregnant women and newborns remain unclear. Here, we report the clinical course of a full-term pregnant woman with COVID-19 and her newborn. CASE REPORT: A 27-year-old pregnant woman with a fever and sore throat was diagnosed with COVID-19. To prevent and control SARS-CoV-2 infection to the newborn and medical staff, delivery was performed via cesarean section. Reverse-transcription quantitative polymerase chain reaction results of the placenta, umbilical cord, cord blood, amniotic fluid, vaginal fluid, breastmilk, newborn anal wipes, and nasopharyngeal samples were negative for SARS-CoV-2. An acute increase in maternal blood pressure and HELLP syndrome-like blood data fluctuations were observed after delivery. CONCLUSION: Perinatal management of patients with COVID-19 could be safely performed for medical staff and newborns under adequate infection control measures.

Psychological Patient-reported outcome measure after anterior cruciate ligament reconstruction: Evaluation of subcategory in ACL-Return to Sport after Injury (ACL-RSI) scale.

BACKGROUND: It has been recognized that psychological factors influence the return to sports after anterior cruciate ligament reconstruction (ACLR). The ACL-return to sports after injury (RSI) scale was developed based on subcategories of emotions, confidence in physical performance and risk appraisal. However, it has not been clarified describing which is the most influential psychological factor of the ACL-RSI scale. HYPOTHESIS: Risk appraisal is the most influent for return to sports in the subcategories of the ACL-RSI scale. PATIENTS AND METHODS: A total of 85 competitive patients who had undergone ACLR were evaluated at 6, 12 and 24 months after surgery. They were classified the return to sports (RTS) group and non-return to sports (NRTS) group. Evaluations were several clinical and functional scores including Cincinnati knee rating system, Knee Osteoarthritis Outcome Score (KOOS), Lysholm score, limitation in activities of daily living (ADL) and sports which estimated by Visual Analog Scale (VAS) score, Isokinetic Muscle Strength (quadriceps and hamstrings), single hop test and anterior laxity. They were investigated their relationship with the ACL-RSI scale including each subcategory. RESULTS: The total ACL-RSI scale significantly improved at each point. Of the subcategories, only risk appraisal was not significantly different at each point (p=0.21 and p=0.13). There was a significant difference at 24 months after ACLR between the RTS group and NRTS group. In terms of risk appraisal, compared with emotion and performance confidence, the difference in the mean value was the most divergent (RTS group: 55.9±22.7 and NRTS group: 23.8±19.3) and took time to improve through 24 months. Among various clinical and functional scores, there were significant differences in the VAS score for sports, KOOS-symptoms, sports and QOL, Cincinnati Knee Rating System-cut, and single hop test values between two groups. Of these, the KOOS-QOL and VAS score for sports showed particularly strong correlations with ACL-RSI risk appraisal (r=0.75 and -0.68, respectively). CONCLUSION: Of the ACL-RSI scale, risk appraisal took the longest time to improve and strongly affected the return to sports. The KOOS-QOL and VAS score for sports were most strongly correlated with the ACL-RSI risk appraisal. It seems that it is important to reduce the psychological risk as soon as possible after ACL injury in ACLR patients. LEVEL OF EVIDENCE: II.

A bone bruise at the lateral and medial tibial plateau with an anterior cruciate ligament injury is associated with a meniscus tear.

PURPOSE: Bone bruises with anterior cruciate ligament (ACL) injury are well studied, but the association between bone bruises and multiple factors is unclear. The main objective of this study was to investigate the association between bone bruising and ACL injury and concomitant injury as well as clinical and functional scores. The second objective was to investigate the presence and distribution patterns of bone bruises. METHOD: A total of 176 patients who underwent ACL reconstruction for primary ACL injury were included. The demographic characteristics and responses to clinical and functional assessments (the Visual Analog Scale for activities of daily living and sports, the Cincinnati Knee Rating System, the Lysholm score, the Knee Osteoarthritis Outcome Score and side-to-side difference in anterior laxity) were recorded at the initial visit. Concomitant injuries were evaluated by intraoperative assessment. RESULTS: Bone bruises were detected in 141 patients (80.1%). The lateral femoral condyle (LFC) was the most common site in 116 patients (65.9%), followed by the lateral tibial plateau (LTP) in 82 patients (46.6%), medial tibial plateau (MTP) in 47 patients (26.7%) and medial femoral condyle (MFC) in 29 patients (16.5%). Regarding the distribution patterns, bone bruising at only the LFC, which was the most common pattern, was detected in 38 patients (27.0%). Bone bruising at the LTP or MTP was significantly associated with lateral (LM) and medial meniscus (MM) tears (odds ratios 4.0, 3.0, 4.3 and 40.5, 95% confidence intervals 1.5-11.6, 1.2-15.1, 1.2-17.3 and 8.6-283.0, respectively). No marked differences in the functional or clinical scores were noted. The severity of bone bruising at the MTP was significantly associated with MM tears and that at the LTP was significantly associated with LM tears. (p < 0.01). CONCLUSION: This study showed association between bone bruising at LTP and LM tears or at MTP and MM tears. Additionally, it provided detailed information on the presence and distribution patterns of bone bruises at each anatomic site. These findings are clinically relevant and will aid in preoperatively diagnosing meniscus tears in cases of ACL injury. LEVEL OF EVIDENCE: Level III.

Clinical and radiographic results after ACL reconstruction using an adjustable-loop device.

BACKGROUND: The femoral cortical suspension device such as fixed loop devices (FLD) and adjustable-loop device (ALD) are used for ACLR technique in recent days. However, there was few studies of clinical and radiographic results for ACLR using ALD. This study was conducted to clarify the clinical and radiographic results, stability and bone tunnel enlargement after ACLR using a ToggleLoc with a zip loop as ALD. METHODS: 80 patients who had data available from the most recent follow-up at ≥2 years since ACLR were evaluated both clinical and radiographic results. They were divided into single bundle reconstruction group (SBR) and double bundle reconstruction group (DBR). Clinical scores were included subjective scores and objective scores at pre- and postoperatively 2 years. The subjective scores were the Cincinnati knee rating system, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, Tegner activity score, Visual Analog Scale (VAS) and ACL-Return to Sport after Injury (RSI) scale. The objective scores were the isokinetic muscle strength, side-to-side difference in anterior instability and single hop test. In radiographical assessment, femoral and tibial tunnel enlargement was evaluated by three-dimensional computed tomography. RESULTS: In both SBR and DBR group, the postoperative subjective scores were significantly improved compared to the preoperative values, except for the Tegner activity score. Similarly, the side-to-side differences in muscle strength, anterior instability and single hop test were significantly improved after surgery. The changes in the femoral and tibial tunnel maximum cross section areas of SBR were 104.3 % ± 21.2 % and 89.2 % ± 15.2 %, respectively, at 2 years post-operatively. In DBR, in the femoral bone volume change of the antero medial (AM) and postero lateral (PL) bundle were 107.0 ± 3.5 % and 108.1 ± 3.3, and in the tibial bone volume change of AM and PL bundle were 90.6 ± 3.3 % and 87.0 ± 4.2 %. At the femoral site, the rate of tunnel enlargement increased for the first 12 months and then decreased through 24 months postoperatively. At the tibial site, by contrast, the rate of tunnel enlargement decreased consistently over the two-year postoperative follow-up. CONCLUSION: This is the first study to include clinical data on ACLR using a ToggleLoc with a zip loop device. ACLR using these devices as ALDs resulted in good clinical outcomes and provided good stability of the knee with relatively little bone tunnel enlargement in both SBR and DBR group.

Alteration of circulating cell-free DNA level by external cephalic version: A potential biomarker for direct evaluation of placental damage.

AIM: To confirm that variations in cell-free fetal DNA (cffDNA) are indicators of external placental damage, we quantitatively investigated cffDNA alterations in maternal peripheral blood during external cephalic version (ECV). METHODS: We recruited 48 singleton pregnant women who underwent ECV in our hospital. Before and immediately after ECV, we harvested 10 ml of maternal peripheral blood samples for cffDNA analysis. cffDNA alterations were assessed based on the fetal fraction (FF) rate. We performed ECV without epidural anesthesia but administered epidural anesthesia if ECV was disrupted due to severe pain. RESULTS: The FF increased from 22.9% ± 5.7% to 27.0% ± 5.7% (p < 0.05) after ECV. The FF increased in both successful (before, 24.4% ± 5.9%; after, 28.1% ± 5.9%; p < 0.05) and unsuccessful (before, 21.8% ± 3.8%; after, 27.3% ± 4.2%; p < 0.05) cases, as well as in patients who received epidural anesthesia (before, 23.9% ± 4.7%; after, 28.5% ± 4.4%; p < 0.05) or underwent ECV more than once (before, 23.5% ± 6.1%; after, 28.4% ± 5.3%; p < 0.05). CONCLUSIONS: FF alterations increased due to external stresses during ECV; the alterations were markedly greater when the strength and duration of external stress increased. These FF alterations may serve as potential biomarkers for the direct assessment of placental damage.

Cells/colony motion of oral keratinocytes determined by non-invasive and quantitative measurement using optical flow predicts epithelial regenerative capacity.

Cells/colony motion determined by non-invasive, quantitative measurements using the optical flow (OF) algorithm can indicate the oral keratinocyte proliferative capacity in early-phase primary cultures. This study aimed to determine a threshold for the cells/colony motion index to detect substandard cell populations in a subsequent subculture before manufacturing a tissue-engineered oral mucosa graft and to investigate the correlation with the epithelial regenerative capacity. The distinctive proliferating pattern of first-passage [passage 1 (p1)] cells reveals the motion of p1 cells/colonies, which can be measured in a non-invasive, quantitative manner using OF with fewer full-screen imaging analyses and cell segmentations. Our results demonstrate that the motion index lower than 40 µm/h reflects cellular damages by experimental metabolic challenges although this value shall only apply in case of our culture system. Nonetheless, the motion index can be used as the threshold to determine the quality of cultured cells while it may be affected by any different culture conditions. Because the p1 cells/colony motion index is correlated with epithelial regenerative capacity, it is a reliable index for quality control of oral keratinocytes.

Risk factor for venous thromboembolism after high tibial osteotomy -analysis of patient demographics, medical comorbidities, operative valuables, and clinical results.

PURPOSE: The aim of this study was to investigate risk factors for VTEs after HTO based on patient demographics, medical comorbidities, operative valuables, and clinical results. METHODS: A total of 137 patients were assessed VTEs using ultrasonography at 1 week after HTO. The risk factors for postoperative VTEs were to assessed. RESULTS: The incidence of VTEs after HTO was 25.5%. Postoperative single leg standing test was independent predictors of VTEs after HTO. CONCLUSION: The incidence of VTEs after HTO is relatively high and Postoperative knee function is important for preventing VTEs after HTO. LEVEL OF EVIDENCE: Ⅱ, Prospective comparative study.

Manufacturing micropatterned collagen scaffolds with chemical-crosslinking for development of biomimetic tissue-engineered oral mucosa.

The junction between the epithelium and the underlying connective tissue undulates, constituting of rete ridges, which lack currently available soft tissue constructs. In this study, using a micro electro mechanical systems process and soft lithography, fifteen negative molds, with different dimensions and aspect ratios in grid- and pillar-type configurations, were designed and fabricated to create three-dimensional micropatterns and replicated onto fish-scale type I collagen scaffolds treated with chemical crosslinking. Image analyses showed the micropatterns were well-transferred onto the scaffold surfaces, showing the versatility of our manufacturing system. With the help of rheological test, the collagen scaffold manufactured in this study was confirmed to be an ideal gel and have visco-elastic features. As compared with our previous study, its mechanical and handling properties were improved by chemical cross-linking, which is beneficial for grafting and suturing into the complex structures of oral cavity. Histologic evaluation of a tissue-engineered oral mucosa showed the topographical microstructures of grid-type were well-preserved, rather than pillar-type, a well-stratified epithelial layer was regenerated on all scaffolds and the epithelial rete ridge-like structure was developed. As this three-dimensional microstructure is valuable for maintaining epithelial integrity, our micropatterned collagen scaffolds can be used not only intraorally but extraorally as a graft material for human use.

Monochorionic diamniotic twins of discordant external genitalia with 45,X/46,XY mosaicism.

BACKGROUND: Monozygotic twins with 45,X/46,XY mosaicism, discordant for phenotypic sex, are extremely rare. METHODS: This report describes the clinical findings of a rare case of 45,X/46,XY mosaicism in monozygotic twins with different external genitalia. Single nucleotide polymorphism (SNP) array analysis, performed by collecting DNA from each umbilical cord, showed identical SNPs in the autosomal chromosomes of both fetuses. RESULTS: Chorionic villus sampling of a 37-year-old primigravida carrying monozygotic twins revealed a 45,X/46,XY karyotype. Autopsy of the aborted fetuses revealed a penis and testes on one fetus and a vagina, uterus, and ovaries in the other fetus--which also had severe cystic hygroma. Cell counting using fluorescence in situ hybridization with XY probes (XY-FISH) showed 20% and 80% abundance of 45,X cells in the internal genitalia, liver, heart, lung, adrenal gland, bone marrow, and spine of the male and female fetuses, respectively. CONCLUSION: These results indicated that the fetuses were genetically monozygotic twins and their different degrees of mosaicism may have resulted in different genital phenotypes.

Direct Assessment of Single-Cell DNA Using Crudely Purified Live Cells: A Proof of Concept for Noninvasive Prenatal Definitive Diagnosis.

Noninvasive testing techniques are often used for fetal diagnosis of genetic abnormalities but are limited by certain characteristics, including noninformative results. Thus, novel methods of noninvasive definitive diagnosis of fetal genetic abnormalities are needed. The aim of this study was to develop a single-cell DNA analysis method with high sensitivity and specificity that enables direct extraction of genetic information from live fetal cells in a crude mixture for simultaneous evaluation. Genomic DNA from circulating fetal CD45-CD14- cells, an extremely rare cell type, extracted from 10-mL samples of maternal peripheral blood, was extracted using a single-cell-based droplet digital (sc-dd) PCR system with a modified amount of polymerase. A hexachloro-6-carboxyfluorescein-labeled RPP30 probe was used as an internal control and a 6-carboxyfluorescein-labeled SRY probe as a target. The results indicated that no droplets generated with samples from pregnant women carrying female fetuses were positive for both probe signals, whereas droplets prepared with samples from pregnant women carrying male fetuses were positive for both probe signals. The latter was considered a direct assessment of genetic information from single circulating male fetal cells. Thus, the modified sc-ddPCR system allows the detection of genetic information from rare target cells in a crudely purified cell population. This research also serves as a proof of concept for noninvasive prenatal definitive diagnosis.

The actual knee function was not influenced by joint line obliquity after open-wedge high tibial osteotomy.

PURPOSE: Excessive joint line obliquity (JLO) after open-wedge high tibial osteotomy (OWHTO) induces detrimental stress on the articular cartilage. The purpose of this article is to assess the correlation between JLO and the clinical results after OWHTO. METHODS: 68 patients were followed up for more than 1 year. JLO was assessed using a long-leg standing anteroposterior radiograph. The knee osteoarthritis outcome score (KOOS) and KSS (Knee Society score) objective knee score were assessed as clinical scores. The Weight-bearing line ratio (WBLR), medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), and joint line convergence angle (JLCA) were assessed as radiological parameters. The timed up-and-go (TUG) test and single-leg standing (SLS) test were performed, and the isometric muscle strength of the quadriceps and hamstrings was assessed to evaluate the knee function. The primary outcomes were the correlations between the JLO and the clinical score, radiological parameters and knee function after OWHTO. The secondary objective of this study was to detect the factor with the greatest influence on JLO. RESULTS: There were significant correlations between the postoperative JLO and the KOOS in the subcategories of pain, activities of daily living (ADL), and sports and recreation (r = -0.311, -0.302, -0.282, p = 0.011, 0.014, 0.022, respectively). However, the postoperative JLO was not significantly correlated with the KSS, knee function, or muscle strength. The preoperative LDFA and postoperative MPTA were factors influencing increased JLO after OWHTO. DISCUSSION: There was no significant correlation between the JLO and the actual knee function. The preoperative LDFA and postoperative MPTA were factors that influenced the increase in JLO after OWHTO.

Predictors of responders for low-dose carperitide monotherapy in patients with acute heart failure.

Human atrial natriuretic peptide, known as carperitide, is approved for early relief of dyspnea in patients with acute heart failure (AHF). However, the diuretic effect of carperitide is sometimes insufficient for controlling volume overload. We investigated predictors for the carperitide response in patients with AHF. Forty-seven patients (age: 74 ± 10 years; left ventricular ejection fraction: 42.0% ± 15.9%) with AHF were enrolled and treated with carperitide monotherapy at a dose of 0.0125 µg/kg/min. Patients without sufficient diuresis (< 60 ml/h) or improvement of symptoms by 4 h after carperitide administration, despite increasing to twice the dose of carperitide and adding another agent, were defined as non-responders. Twenty-four (51%) patients were defined as responders and treated with low-dose carperitide monotherapy on the first day. Multiple logistic regression analysis showed that the response to carperitide monotherapy was independently predicted by serum creatinine levels and systolic blood pressure (SBP) on admission. The area under the receiver-operating characteristic curve for predicting the response to carperitide by SBP was 0.808 (95% confidence interval [0.686-0.930], sensitivity: 83.3%, specificity: 65.2%, cutoff value: 135 mmHg). Four (8.5%) patients developed asymptomatic transient hypotension. Worsening renal function occurred within 3 days of admission in three (6.4%) patients who received low-dose carperitide therapy. SBP and serum creatinine levels on admission might be useful for predicting the diuretic response to low-dose carperitide monotherapy in patients with AHF. Initial use of low-dose carperitide therapy does not have adverse effects on renal function.

Two unrelated pedigrees with achondrogenesis type 1b carrying a Japan-specific pathogenic variant in SLC26A2.

We present two unrelated Japanese pedigrees with achondrogenesis type 1b (ACG1B), characterized by prenatally lethal fetal hydrops and severe micromelia. The affected members in these pedigrees carried a common homozygous missense point mutation in solute carrier family 26 member 2 (SLC26A2), a gene associated with ACG1B (NM_000112:c.1987G>A). This loss-of-function point mutation causes substitution of glycine 663 with arginine in a highly conserved loop domain of SLC26A2. Interestingly, only a few cases of this mutation have been registered in Japanese genomic databases, and there are no reports of this mutation in any major genomic databases outside Japan. Furthermore, we confirmed the presence of a homozygous stretch of approximately 75 kb surrounding the pathogenic variant. Our findings suggest that this missense point mutation in SLC26A2, which is likely the cause of the ACG1B phenotypes in these unrelated fetuses, is distributed exclusively in Japan.