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Background: To overcome organ shortage during transplantation, interspecies organ generation via blastocyst complementation has been proposed, although not yet in evolutionarily distant species. To establish high levels of chimerism, low chimerism is required early in development, followed by high chimerism, to effectively complement the organ niche. Very few human cells are expected to contribute to chimerism in heterologous animals. Previous studies had demonstrated increased donor chimerism in both intra- and interspecies chimeras in rodents, using insulin-like growth factor 1 receptor ( Igf1r ) knockout (KO) mice; deletion of the Igf1r gene in the mouse host embryo created a cell-competitive niche. The current study aimed to generate IGF1R- KO pigs and evaluate whether they have the same phenotype as Igf1r -KO mice., Methods: To generate IGF1R- KO pigs, genome-editing molecules were injected into the cytoplasm of pig zygotes. The fetuses were evaluated at 104 days of gestation., Results: IGF1R -KO pigs were generated successfully. Their phenotypes were almost identical to those of Igf1r -KO mice, including small lungs and enlarged endodermal organs in fetuses, and they were highly reproducible., Conclusions: Pigs may allow the generation of organs using blastocyst complementation with developmentally-compatible xenogeneic pluripotent stem cells over a large evolutionary distance., Competing Interests: H.Nagashima is a founder and shareholder of PorMedTec Co., Ltd. These associations do not alter the authors' adherence to the journal's policies on sharing data and materials. The other authors declare that they have no conflicts of interest., (© 2024 The Author(s).)

Background: Emerging evidence has supported the idea that goal-directed prehabilitation is a promising approach to boost functional capacity in preoperative patients. However, its usefulness has not been tested in the hepatobiliary and pancreatic fields. The objective of this trial was to investigate the efficacy of goal-directed prehabilitation for improving functional capacity in patients who were planned to undergo major hepatobiliary and pancreatic operations., Methods: This assessor-blinded, parallel-arm, randomized clinical trial recruited patients who were scheduled for major hepatobiliary and pancreatic surgeries for malignancy. Patients were randomly allocated into the step goal-directed prehabilitation group as the test group and into the conventional prehabilitation group as the control group. Patients in the goal-directed prehabilitation group participated in a walking prehabilitation program with an intergrading goal of the step count. Patients in the conventional prehabilitation group received standard physical and nutritional prehabilitation. The primary outcome was change in the 6-minute walking distance, which ranged from the time before starting prehabilitation (baseline) to the time after completing prehabilitation (immediately before surgery)., Results: Among 180 randomized patients, 144 patients were included in the primary analysis (73 patients in the conventional prehabilitation group and 71 patients in the goal-directed prehabilitation group). The mean change in the 6-minute walking distance was 27 meters in the conventional prehabilitation group and 31 meters in the goal-directed prehabilitation group (P = .633)., Conclusion: In patients undergoing major hepatobiliary and pancreatic surgeries for malignancies, a goal-directed prehabilitation program did not result in a significantly greater increase in functional capacity than did conventional prehabilitation., Registration Number: UMIN000038791 (https://www.umin.ac.jp/)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The outcome of total hip arthroplasty (THA) in patients with end-stage arthritis of the hip is associated with preoperative physical status. This study was performed to examine the relationship between the preoperative severity of sarcopenia and clinical outcomes after THA. This retrospective cohort study was performed among 306 consecutive patients (mean age: 63.7 ± 12.9 years, 222 women) undergoing THA at a university hospital. The severity of sarcopenia was determined based on the skeletal muscle mass index (SMI), handgrip strength, and gait speed according to the criteria of the Asian Working Group for Sarcopenia 2019. The severe sarcopenia prevalence rate was 10.6%. Severe sarcopenia was significantly associated with the risk of delayed functional recovery (adjusted odds ratio, 2.82; 95% confidence interval, 1.03-7.72; p = 0.043) compared with the non-sarcopenia group after adjusting for pre-existing risk factors, including preoperative hip function and physical activity. The addition of SMI, handgrip strength, and gait speed to the model for risk of functional recovery delay significantly increased the area under the receiver operating characteristic curve ( p = 0.038). Severe sarcopenia was significantly associated with poorer hip function and patient-reported outcomes at 6 months after surgery compared with the non-sarcopenia group. Severe sarcopenia was adversely associated with postoperative clinical outcomes in patients undergoing THA.

We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case-control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients., (© 2024. The Author(s).)

Cataract is an eye disease, in which the lens becomes opaque, causing vision loss and blindness. The detailed mechanism of cataract development has not been characterized, and effective drug therapies remain unavailable. Here, we investigated the effects of Hypoxia-inducible factor 1 (HIF-1) inhibitors using an ex vivo model, in which rat lenses were cultured in galactose-containing medium to induce opacity formation. We found that treatment with the HIF-1 inhibitors 2-Methoxyestradiol (2ME2), YC-1, and Bavachinin decreased lens opacity. Microarray analysis on 2ME2-treated samples, in which opacity was decreased, identified genes upregulated by galactose and downregulated by inhibitor treatment. Subsequent STRING analysis on genes that showed expression change by RT-qPCR identified two clusters. First cluster related to the cytoskeleton and epithelial-mesenchymal transition (EMT). Second cluster related to the oxidative stress, and apoptosis. ACTA2, a known marker for EMT, and TXNIP, a suppressor of cell proliferation and activator of apoptosis, were present in each cluster. Thus, suppression of EMT and apoptosis, as well as activation of cell proliferation, appear to underlie the decrease in lens opacity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Takashima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hydroxyapatite and β-tricalcium phosphate have been clinically applied as artificial bone materials due to their high biocompatibility. The development of artificial bones requires the verification of safety and efficacy through animal experiments; however, from the viewpoint of animal welfare, it is necessary to reduce the number of animal experiments. In this study, we utilized machine learning to construct a model that estimates the bone-forming ability of bioceramics from material fabrication conditions, material properties, and in vivo experimental conditions. We succeeded in constructing two models: 'Model 1', which predicts material properties from their fabrication conditions, and 'Model 2', which predicts the bone-formation rate from material properties and in vivo experimental conditions. The inclusion of full width at half maximum (FWHM) in the feature of Model 2 showed an improvement in accuracy. Furthermore, the results of the feature importance showed that the FWHMs were the most important. By an inverse analysis of the two models, we proposed candidates for material fabrication conditions to achieve target values of the bone-formation rate. Under the proposed conditions, the material properties of the fabricated material were consistent with the estimated material properties. Furthermore, a comparison between bone-formation rates after 12 weeks of implantation in the porcine tibia and the estimated bone-formation rate. This result showed that the actual bone-formation rates existed within the error range of the estimated bone-formation rates, indicating that machine learning consistently predicts the results of animal experiments using material fabrication conditions. We believe that these findings will lead to the establishment of alternative animal experiments to replace animal experiments in the development of artificial bones.

Objectives: Limited data exist regarding association between physical performance and in-hospital falls. This study was performed to investigate the association between physical performance and in-hospital falls in a high-risk population., Design: Retrospective cohort study., Setting and Participants: The study population consisted of 1200 consecutive patients with a median age of 74 years (50.8% men) admitted to a ward with high incidence rates of falls, primarily in the departments of geriatrics and neurology, in a university hospital between January 2019 and December 2021., Methods: Short Physical Performance Battery (SPPB) was measured after treatment in the acute phase. As the primary end point of the study, the incidence of in-hospital falls was examined prospectively based on data from mandatory standardized incident report forms and electronic patient records., Results: SPPB assessment was performed at a median of 3 days after admission, and the study population had a median SPPB score of 3 points. Falls occurred in 101 patients (8.4%) over a median hospital stay of 15 days. SPPB score showed a significant inverse association with the incidence of in-hospital falls after adjusting for possible confounders (adjusted odds ratio for each 1-point decrease in SPPB: 1.19, 95% CI 1.10-1.28; P < .001), and an SPPB score ≤6 was significantly associated with increased risk of in-hospital falls. Inclusion of SPPB with previously identified risk factors significantly increased the area under the curve for in-hospital falls (0.683 vs. 0.740, P = .003)., Conclusion and Implications: This study demonstrated an inverse association of SPPB score with risk of in-hospital falls in a high-risk population and showed that SPPB assessment is useful for accurate risk stratification in a hospital setting., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Cataracts are opacifications of the lens that cause loss of visual acuity and ultimately of eyesight. Age-related cataract develops in most elderly people, but the mechanisms of cataract onset are incompletely understood. The Ihara Cataract Rat (ICR) is an animal model of hereditary cataracts showing cortical opacity that commonly develops prematurely. We identified putative mechanisms of cataract onset in the ICR rat model by measuring gene expression changes before and after cortical cataract development and conducting point mutation analysis. Genes differentially expressed between 4-week-old animals without cortical cataracts and 8-10-week-old animals with cortical cataracts were selected from microarray analysis. Three connections were identified by STRING analysis: (i) Epithelial-Mesenchymal Transition (EMT), including Col1a2, and Pik3r1. (ii) Lens homeostasis, including Aqp5, and Cpm. (iii) Lipid metabolism, including Scd1, Srebf1, and Pnpla3. Subsequently, mutation points were selected by comparing ICR rats with 12 different rats that do not develop cataracts. The apolipoprotein Apoc3 was mutated in ICR rats. Analyses of gene expression changes and point and mutations suggested that abnormalities in EMT or lipid metabolism could contribute to cataract development in ICR rats., (© 2023. Springer Nature Limited.)

Prepacked chromatography columns and cassette filtration units offer many advantages in bioprocessing. These include reduced labor costs and processing times, ease of storage, and enhanced process flexibility. Rectangular formats are particularly attractive as they can be easily stacked and multiplexed together for continuous processing. Cylindrical chromatography beds have dominated bioprocessing even though their bed support and pressure-flow performance vary with bed dimensions. This work presents the performance of novel, rhombohedral chromatography devices with internally supported beds. They are compatible with existing chromatography workstations and can be packed with any standard commercial resin. The devices offer pressure-flow characteristics independent of container-volume, simple multiplexing, and separation performance comparable to cylindrical columns. Their bi-planar, internal bed support allows mechanically less-rigid resins to be used at up to four times higher maximal linear velocities, and productivities approaching 200 g/L/h for affinity resins, compared to the 20 g/L/h typical of many column-based devices. Three 5 L devices should allow processing of up to 3 kg of monoclonal antibody per hour., (© 2023 JSR Life Sciences. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Rationale: The purpose of this case report is to describe a case of successful early rehabilitation intervention for simultaneous liver and kidney transplantation (SLKT)., Patient Concerns: A 51-year-old Japanese man was diagnosed with Caroli disease 27 years ago. Hemodialysis was introduced due to end-stage renal disease 17 years ago., Diagnoses: After successful SLKT, the patient was extubated on postoperative day (POD) 1, liberated from dialysis on POD 4, and discharged from the intensive care unit on POD 9., Interventions: Supervised rehabilitation was started on POD 2, and the patient was able to walk 100 m on POD 9. Electrical muscle stimulation therapy was started to improve muscle weakness in both legs on POD 16, and aerobic exercise using a cycle-ergometer was started on POD 24., Outcomes: The 6-minute walking distance improved from 324 m on POD 14 to 501 m on POD 28. The patient could walk 4000 to 5000 steps per day at hospital discharge, and was discharged home on POD 32. There were no adverse events, including worsening hepatic or renal function, during the rehabilitation period. One month after discharge, the patient was able to perform 30 to 40 minutes of aerobic exercise every day, and returned to work 5 months after discharge., Lessons: This case shows that early rehabilitation intervention immediately after SLKT safely and rapidly improved physical performance without adverse events. The results in the present case suggest that regular physical assessment and appropriate interventions with a variety of exercise modalities can contribute to improved physical performance in SLKT patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder caused by mutation in the dystrophin gene ( DMD ) on the X chromosome. Female DMD carriers occasionally exhibit symptoms such as muscle weakness and heart failure. Here, we investigated the characteristics and representativeness of female DMD carrier ( DMD- X KO X WT ) pigs as a suitable disease model., Methods: In vitro fertilization using sperm from a DMD -X KO Y↔X WT X WT chimeric boar yielded DMD- X KO X WT females, which were used to generate F2 and F3 progeny, including DMD- X KO X WT females. F1-F3 piglets were genotyped and subjected to biochemical analysis for blood creatine kinase (CK), aspartate aminotransferase, and lactate dehydrogenase. Skeletal muscle and myocardial tissue were analyzed for the expression of dystrophin and utrophin, as well as for lymphocyte and macrophage infiltration., Results: DMD -X KO X WT pigs exhibited various characteristics common to human DMD carrier patients, namely, asymptomatic hyperCKemia, dystrophin expression patterns in the skeletal and cardiac muscles, histopathological features of skeletal muscle degeneration, myocardial lesions in adulthood, and sporadic death. Pathological abnormalities observed in the skeletal muscles in DMD -X KO X WT pigs point to a frequent incidence of pathological abnormalities in the musculoskeletal tissues of latent DMD carriers. Our findings suggest a higher risk of myocardial abnormalities in DMD carrier women than previously believed., Conclusions: We demonstrated that DMD- X KO X WT pigs could serve as a suitable large animal model for understanding the pathogenic mechanism in DMD carriers and developing therapies for female DMD carriers., Competing Interests: H.N. is a founder and shareholder of PorMedTec Co., Ltd. These associations do not alter the authors' adherence to the journal's policies on sharing data and materials. The other authors declare that they have no conflicts of interest., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score < 48 points, and prolonged IMV was significantly associated with lower MRC sum score and handgrip strength. Symptoms were similar between groups at ICU discharge, and the symptoms most commonly reported as moderate-to-severe were impaired well-being (52%), anxiety (43%), tiredness (41%), and depression (35%). Although muscle strength and mobility status were significantly improved after ICU discharge, Edmonton Symptom Assessment System score did not improve significantly in the prolonged IMV group. EuroQol five-dimension five-level summary index was significantly lower in the prolonged than short IMV group at 6 months after ICU discharge. We found substantial negative physical function and mental health consequences in the majority of surviving COVID-19 patients requiring IMV, with prolonged period of IMV showing greater negative effects not only immediately but also at 6 months after discharge from the ICU., (© 2023. Springer Nature Limited.)

Although cataracts affect almost all people at advanced age and carry a risk of blindness, the mechanisms of cataract development remain incompletely understood. Oxidative stress, which is a causative factor in cataract, results in DNA breakage, which suggests that DNA damage could contribute to the formation of cataracts. We developed an ex vivo experimental system to study changes in gene expression during the formation of opacities in the lens by culturing explanted rat lenses with Methylmethanesulfonate (MMS) or Bleomycin, which induce DNA damage. Lenses cultured using this experimental system developed cortical opacity, which increased in a concentration- and time-dependent manner. In addition, we compared expression profiles at the whole gene level using microarray analysis of lenses subjected to MMS or Bleomycin stress. Microarray findings in MMS-induced opacity were validated and gene expression was measured from Days 1-4 using RT-qPCR. Altered genes were classified into four groups based on the days of peak gene expression: Group 1, in which expression peaked on Day 1; Group 2, in which expression peaked on Day 2; Group 3, in which expression progressively increased from Days 1-4 or were upregulated on Day 1 and sustained through Day 4; and Group 4, in which expression level oscillated from Days 1-4. Genes involved in lipid metabolism were restricted to Group 1. DNA repair- and cell cycle-related genes were restricted to Groups 1 and 2. Genes associated with oxidative stress and drug efflux were restricted to Group 2. These findings suggest that in temporal changes of MMS-induced opacity formation, the activated pathways could occur in the following order: lipid metabolism, DNA repair and cell cycle, and oxidative stress and drug efflux., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Yamaoka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to investigate the therapeutic effects of histone acetyltransferase (HAT) inhibitors. Among the tested HAT inhibitors, TH1834 was the only one that could reverse most of the opacity once it had formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. In lens cross-sections, vacuoles were present in the tissue of the cortical equatorial region of untreated cataract samples. In treated cataract samples, lens tissue regenerated to fill the vacuoles. To identify the genes regulated by HAT inhibitors, qRT-PCR was performed on treated and untreated cataract samples to determine candidate genes. Expression of Acta1 and Stmn4, both of which are involved in the cytoskeleton, were altered significantly in C646+CPTH2 samples. Expression of Emd, a nuclear membrane protein, and Prtfdc1, which is involved in cancer cell proliferation, were altered significantly in CBP30+CPTH2 samples. Acta1, Acta2, Arrdc3, Hebp2, Hist2h2ab, Pmf1, Ppdpf, Rbm3, RGD1561694, Slc16a6, Slfn13, Tagln, Tgfb1i1, and Tuba1c in TH1834 samples were significantly altered. These genes were primarily related to regulation of cell proliferation, the cytoskeleton, and cell differentiation. Expression levels increased with the onset of cataracts and was suppressed in samples treated with HAT inhibitors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Nagaya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cataract causes vision loss and blindness due to formation of opacities of the lens. The regulatory mechanisms of cataract formation and progression remain unclear, and no effective drug treatments are clinically available. In the present study, we tested the effect of ataxia telangiectasia mutated (Atm) inhibitors using an ex vivo model in which rat lenses were cultured in galactose-containing medium to induce opacity formation. After lens opacities were induced by galactose, the lenses were further incubated with the Atm inhibitors AZD0156 or KU55933, which decreased lens opacity. Subsequently, we used microarray analysis to investigate the underlying molecular mechanisms of action, and extracted genes that were upregulated by galactose-induced opacity, but not by inhibitor treatment. Quantitative measurement of mRNA levels and subsequent STRING analysis revealed that a functional network consisting primarily of actin family and actin-binding proteins was upregulated by galactose treatment and downregulated by both Atm inhibitors. In particular, Acta2 is a known marker of epithelial-mesenchymal transition (EMT) in epithelial cells, and other genes connected in this functional network (Actn1, Tagln, Thbs1, and Angptl4) also suggested involvement of EMT. Abnormal differentiation of lens epithelial cells via EMT could contribute to formation of opacities; therefore, suppression of these genes by Atm inhibition is a potential therapeutic target for reducing opacities and alleviating cataract-related visual impairment., Competing Interests: The authors have declared that no competing interests exist.

Background: Postoperative loss of exercise capacity and pulmonary function is a major concern among lung cancer patients. In this study, the time for a stair-climbing to 12-m height was used to investigate whether preoperative chest 3D-computed tomography (CT) could be a useful tool for predicting postoperative variations in exercise capacity and pulmonary function., Methods: Seventy-eight patients undergoing lobectomy for suspected stage I lung cancer were prospectively enroled. Preoperatively, lobe volume and low attenuation volume (LAV) were evaluated using the SYNAPSE VINCENT system. Preoperative data on stair-climbing time, spirometry and diffusing capacity of the lung for carbon monoxide (DL CO ) at baseline and 6-month postoperative data were used to evaluate variations in exercise capacity and pulmonary function. Maximal oxygen uptake (VO 2 t) was evaluated based on the stair-climbing time., Results: Significant differences in the variation of exercise capacity at 6 months postoperatively were found between the groups categorized by target lobe volume and LAV status: The large volume/LAV (+) group had a greater decline in VO 2 t. Mean loss of VO 2 t was -6.2%, -1.4%, -1.6% and -0.1% in the large volume/LAV (+), large volume/LAV (-), small volume/LAV (+) and small volume/LAV (-) groups, respectively. The large volume/LAV (-) group had a greater decline in forced expiratory volume in 1 s. The small volume/LAV (+) group showed a reduced decline in the DL CO ., Conclusions: Analysis of chest 3D-CT scans is a potential tool for predicting the loss of exercise capacity and pulmonary function after lung lobectomy., (© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Introduction: Previously, we performed gene knockout (KO) of interleukin-2 receptor gamma ( IL2RG ) in porcine fetal fibroblasts using zinc finger nuclease-encoding mRNAs, subsequently generating IL2RG KO pigs using these cells through somatic cell nuclear transfer. The IL2RG KO pigs lacked a thymus and were deficient in T lymphocytes and natural killer cells, similar to human X-linked severe combined immunodeficiency (SCID) patients. The present study aimed to evaluate whether pigs can support the growth of xenografted human cells and have the potential to be an effective animal model., Methods: The IL2RG X KO Y pigs used in this study were obtained by mating IL2RG X KO X females with wild-type boars. This permitted the routine production of IL2RG KO pigs via natural breeding without complicated somatic cell cloning procedures; therefore, a sufficient number of pigs could be prepared. We transplanted human HeLa S3 cells expressing the tandem dimer tomato into the ears and pancreas of IL2RG KO pigs. Additionally, a newly developed method for the aseptic rearing of SCID pigs was used in case of necessity., Results: Tumors from the transplanted cells quickly developed in all pigs and were verified by histology and immunohistochemistry. We also transplanted these cells into the pancreas of designated pathogen-free pigs housed in novel biocontainment facilities, and large tumors were confirmed., Conclusions: IL2RG KO pigs have the potential to become useful animal models in a variety of translational biology fields., Competing Interests: The authors have no conflicts of interest., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, manifesting as the progressive development of fluid-filled renal cysts. In approximately half of all patients with ADPKD, end-stage renal disease results in decreased renal function. In this study, we used CRISPR-Cas9 and somatic cell cloning to produce pigs with the unique mutation c.152&#95;153insG (PKD1 insG/+ ). Pathological analysis of founder cloned animals and progeny revealed that PKD1 insG/+ pigs developed many pathological conditions similar to those of patients with heterozygous mutations in PKD1. Pathological similarities included the formation of macroscopic renal cysts at the neonatal stage, number and cystogenic dynamics of the renal cysts formed, interstitial fibrosis of the renal tissue, and presence of a premature asymptomatic stage. Our findings demonstrate that PKD1 insG/+ pigs recapitulate the characteristic symptoms of ADPKD., (© 2022. The Author(s).)

Introduction: The spread of third-generation cephalosporin-resistant Gram-negative bacteria is a serious concern in acute and post-acute care settings. This study aimed to understand the epidemiology and molecular background of fecal colonization of resistant Enterobacterales in elderly people., Methods: In December 2015-December 2017, stool or rectal swab samples were collected from 101 elderly patients receiving home care, using long-term care facilities (LTCF), and living in nursing homes repeatedly at 3-9-month intervals. Patient clinical background data were collected from medical records. After phenotypic screening for extended-spectrum β-lactamase (ESBL), AmpC-type β-lactamase or carbapenemase production, drug resistance genes of isolates were analyzed using polymerase chain reaction (PCR). ESBL-producing Escherichia coli isolates obtained from the same patients in repetitive screenings were analyzed using PCR-based ORF typing. Risk factors for persistent carriage of resistant Enterobacterales were analyzed using multivariate analysis., Results: Resistant Enterobacterales isolates were detected in 37 of 101 (36.6%) and 29 of 80 (36.3%) residents in first and second screenings, respectively. ESBL-producing E. coli accounted for 80% isolates, the most common being CTX-M-9-group β-lactamase producers. Molecular epidemiological analysis revealed probable transmissions of ESBL-producing E. coli; 58% of ESBL-producing E. coli colonizers were persistent colonizers at least after 3 -month intervals. Age > 87 years and LTCF residence were independent risk factors for persistent carriage of ESBL-producing E. coli., Conclusions: We showed, for the first time, high persistent colonization rate of ESBL-producing E. coli among elderly people in post-acute care settings with probable horizontal transmission. We also identified significant risk factors for persistent colonization., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study., Methods: Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed., Results: Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27-2.92, 2.01-5.58, 3.64-23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively., Conclusions: Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment., (© 2021. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)