Laparoscopic totally extraperitoneal repair for recurrent inguinal bladder hernia: A case report.

We present a case of a recurrent inguinal bladder hernia that was previously unsuccessfully operated on three times and was repaired using totally extraperitoneal repair (TEP). A 79-year-old man presented with a right inguinal swelling that had been treated three times on the same side with anterior approaches. Computed tomography confirmed a recurrent inguinal bladder hernia. TEP was performed after identifying the bladder hernia preoperatively, with previous surgeries that used a plug-and-patch technique through an anterior approach. The extraperitoneal approach allowed the bladder to be reduced without injury and the hernia to be safely repaired using a 3D Max® Light Mesh. The postoperative recovery was uneventful, with no recurrence after 1 year. TEP facilitates the diagnosis and repair of bladder hernias, emphasizing the importance of preoperative diagnosis and the efficacy of endoscopic procedures in bladder hernia repair, even in recurrent cases.

Single-nucleus RNA sequencing reveals loss of DCT1 renal tubules in HIV Vpr transgenic mice.

Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the distal tubules and on the expression level of the Slc12a3 gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, single-nucleus RNA sequencing was performed on kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice, Slc12a3 expression was not significantly different in DCT cells. The Pvalb+ DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT mice (P < 0.01). Immunohistochemistry demonstrated fewer Slc12a3+Pvalb+ DCT1 segments in Vpr Tg mice. Differential gene expression analysis between Vpr Tg and WT in the DCT cluster showed downregulation of Ier3 gene, which is an inhibitor of apoptosis. The in vitro knockdown of Ier3 by siRNA transfection induced apoptosis in mouse DCT cells. These observations suggest that the salt-wasting effect of Vpr in Vpr Tg mice is likely mediated by Ier3 downregulation in DCT1 cells and loss of Slc12a3+Pvalb+ DCT1 segments.

CDP-DAG synthesis by peripheral membrane-bound Tam41-type enzymes.

Cytidine diphosphate diacylglycerol (CDP-DAG) is a critical intermediate that is converted to multiple phospholipids in prokaryotes and eukaryotes. In budding yeast, CDP-DAG synthesis from cytidine triphosphate (CTP) and phosphatidic acid (PA) is catalyzed by the membrane-integrated protein Cds1 in the endoplasmic reticulum and the peripheral membrane-bound protein Tam41 in mitochondria. Although a recent study revealed that the fission yeast SpTam41 consists of a nucleotidyltransferase domain and a winged helix domain, forming an active-site pocket for CTP binding between the two domains together with a C-terminal amphipathic helix for membrane association, how CTP and Mg2+, a most-favored divalent cation, are accommodated with PA remains obscure. A more recent report by Kimura et al. (J. Biochem. 2022; 171:429-441) solved the crystal structure of FbTam41, a functional ortholog from a Firmicutes bacterium, with CTP-Mg2+, successfully providing a detailed molecular view of CDP-DAG synthesis. In this commentary, our current understanding of Tam41-mediated reaction is discussed.

Bone loss on the femoral side in knees with medial osteoarthritis: Implications for kinematically-aligned total knee arthroplasty - A comparative study of lateral distal femoral angle in knees with and without osteoarthritis in the same patients.

BACKGROUND: This study aimed to investigate the difference in lateral distal femoral angle (LDFA) between knees with medial osteoarthritis (mOA) and knees without osteoarthritis, and to explore the validity of the assumption that there is no bone wear on the femoral articular surface in kinematic alignment total knee arthroplasty (KA-TKA). METHODS: The study included 69 patients with mOA on one side of the knee and but no OA on the other side. LDFA, medial proximal tibial angle (MPTA), mechanical hip-knee-ankle angle (mHKA), and arithmetic hip-knee-ankle angle (aHKA) were measured and compared between the knees. Pearson's correlation coefficient and paired t-tests were used for statistical analysis. RESULTS: The LDFA and MPTA were significantly more varus in mOA knees than in knees non-OA knees, with differences of 1.0° ± 2.3° and 0.9° ± 2.0°, respectively. The difference between mHKA of the non-OA side and aHKA of the mOA side was not significant, indicating that it is appropriate to use aHKA as an estimation of postoperative alignment after kinematically-aligned total knee arthroplasty without anatomical correction. However, there was a significant difference in MPTA and aHKA between male and female patients in both mOA and non-OA knees. CONCLUSIONS: The assumption that there is no bone wear on the femoral articular surface is rejectable, and the constant compensation thickness of 2 mm for cartilage wear may not be sufficient. Further research is needed to estimate the amount of bone wear in both femur and tibia side to develop more individualized surgical planning strategies in KA-TKA.

Pre-milling technique improves the accuracy of posterior femoral condyle cut and reduces the tibial recut in Oxford unicompartmental knee arthroplasty.

BACKGROUND: Recuts are sometimes needed in UKA because of inadequate posterior tibial cut thickness. We investigated the efficacy of a pre-milling technique (the first milling is done prior to the posterior condylar cut) in Oxford unicompartmental knee arthroplasty to enhance bone cut thickness and to minimize tibial recuts. PATIENTS AND METHODS: Between January 2021 and January 2023, a posterior condyle cut was made before milling in 213 knees in 152 patients (conventional group), while the pre-milling technique was used in 198 knees in 140 patients (pre-milling group). The thickness of the posterior condyle and the rate of tibial recuts were compared between the groups. RESULTS: The bone cut thickness was thinner in the conventional group than in the pre-milling group in small-size (4.7 mm ± 0.6 mm and 5.0 mm ± 0.6 mm, P = 0.0001) and in medium-size (5.1 mm ± 0.5 mm and 5.4 mm ± 0.5 mm, 0.0001) femoral components, whereas there was no difference in large-size femoral components. However, the thickness was still less than the component thickness (5.17 mm for small, 5.57 mm for medium and 6.17 mm for large) in both groups. Tibial recuts were more prevalent in the conventional group than in the pre-milling group (14 knees, 7%, 3 knees 2%, P = 0.002). CONCLUSIONS: The pre-milling technique was found to increase the bone cut thickness in small and medium femoral components, reducing the need for tibial recuts. Further research is warranted to optimize the pre-milling technique and to investigate its long-term impact on patient outcomes.

Propensity of the tight mid-flexion and loose flexion gap despite the adjustment of extension and flexion gaps in Oxford unicompartmental knee arthroplasty: retrospective study.

PURPOSE: A well-balanced joint gap is necessary in Oxford unicompartmental knee arthroplasty (OUKA) to prevent mobile-bearing dislocation. While the gaps between 20° (extension) and 100° (flexion) are precisely adjusted using the incremental mill system, there has been insufficient evaluation of gaps in other angles. We hypothesized that the gap is not always the same in other angles. This retrospective study aimed to evaluate the gap in full-extension (0°), mid-flexion (60°) and deep flexion (130°) for comparison with those in extension and flexion gaps. METHODS: We evaluated 119 knees in 83 patients (51 females, 31 males, aged 71.9 years). The full-extension and mid-flexion gaps were compared with the extension gap, and the deep flexion gap was contrasted with the flexion gap. Each gap was classified into isometric, tight or loose, for evaluation of contributing factors. RESULTS: Although the full-extension gap tended to be isometric (45%), the mid-flexion tended to be tight (48%), whereas the deep-flexion was loose in most knees (84%) (P = 0.002). The tight mid-flexion and loose deep flexion gap pattern accounted for 44% of the total knees, especially so with smaller femoral components (P = 0.004). CONCLUSION: Our results highlight the propensity of tight mid-flexion and loose flexion gap despite the adjustment of extension and flexion gaps in OUKA. Although the effect of such a minor gap imbalance is still unknown, the pattern was more prevalent in patients with smaller-sized femoral components. Use of a larger femoral component may equalize the gap throughout the motion arc.

Laparoscopic Repair Following a Delayed Presentation of Traumatic Diaphragmatic Hernia: A Case Report.

Traumatic diaphragmatic hernia is a rare condition that occurs after trauma, and some patients have a delayed presentation. A laparoscopic approach is rarely used to repair traumatic diaphragmatic hernias. We encountered a case of asymptomatic diaphragmatic hernia diagnosed after a comprehensive medical examination. A 71-year-old woman was diagnosed with a delayed presentation of traumatic diaphragmatic hernia with prolapse of the greater omentum owing to a traffic injury 20 years ago. Surgery was performed laparoscopically using three ports, and intraoperative respiratory management was performed using a double-lumen tube. The 2.5-cm-diameter hernial orifice was sutured under contralateral one-lung ventilation after the greater omentum was returned to the abdominal cavity. The patient's postoperative course was uneventful, and she was discharged on the third day. Intraoperative strategies such as respiratory management and the laparoscopic approach play a crucial role in ensuring favorable postoperative outcomes. The last follow-up was at six months post-operation, and the patient was doing well.

Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer.

Ovarian clear cell carcinoma (OCCC) is a gynecological cancer with a dismal prognosis; however, the mechanism underlying OCCC chemoresistance is not well understood. To explore the intracellular networks associated with the chemoresistance, we analyze surgical specimens by performing integrative analyses that combine single-cell analyses and spatial transcriptomics. We find that a chemoresistant OCCC subpopulation with elevated HIF activity localizes mainly in areas populated by cancer-associated fibroblasts (CAFs) with a myofibroblastic phenotype, which is corroborated by quantitative immunostaining. CAF-enhanced chemoresistance and HIF-1α induction are recapitulated in co-culture assays, which show that cancer-derived platelet-derived growth factor (PDGF) contributes to the chemoresistance and HIF-1α induction via PDGF receptor signaling in CAFs. Ripretinib is identified as an effective receptor tyrosine kinase inhibitor against CAF survival. In the co-culture system and xenograft tumors, ripretinib prevents CAF survival and suppresses OCCC proliferation in the presence of carboplatin, indicating that combination of conventional chemotherapy and CAF-targeted agents is effective against OCCC.

Preoperative Arithmetic Hip-Knee-Ankle Angle as a Predictor of Postoperative Leg Alignment in Medial Oxford Unicompartmental Knee Arthroplasty.

Introduction This study aimed to evaluate whether the arithmetic hip-knee-ankle angle (aHKA) can be used to predict the postoperative HKA. Methods This study included 248 knees in 166 patients who underwent Oxford unicompartmental knee arthroplasty (UKA) between February 2021 and November 2022. Through preoperative and postoperative long-leg radiography, the medial proximal tibial angle (MPTA) and the lateral distal femoral angle (LDFA) were expressed as the deviation from the perpendicular line to the mechanical axes, and the mechanical HKA (mHKA) was defined as the angle between the femoral and tibial mechanical axes. Using the MPTA and LDFA, the arithmetic HKA (aHKA; MPTA + LDFA) and the joint line obliquity (JLO; MPTA - LDFA) were calculated, and the preoperative and postoperative values were compared. Results The preoperative aHKA and the postoperative mHKA values were similar (-0.38° ± 2.96°) and significantly smaller than the difference between the preoperative and postoperative mHKAs (4.58° ± 3.60°, P < 0.05). Meanwhile, the MPTA tended to be varus, and the LDFA tended to be valgus. Eventually, the JLO inclined more medially from -6.33° ± 3.42° preoperatively to -8.97° ± 3.92° postoperatively, representing a significant difference (P < 0.05). Conclusion The preoperative aHKA was similar to the postoperative mHKA. Therefore, it can be regarded as a predictor of postoperative leg alignment after Oxford UKA. Meanwhile, there was a medial incline of the joint line. Further investigation is required to evaluate the effect of such a joint line alteration.

Tibial Lateral Condyle Fracture After Cementless Oxford Unicompartmental Knee Arthroplasty (UKA): A Report of Four Cases.

Cementless unicompartmental knee arthroplasty (UKA) has a lower rate of radiolucency in postoperative follow-up than cemented UKA. However, the rate of tibial plateau fracture, one of the complications, has been reported to be higher in cementless UKA than in cemented UKA. We report four cases of postoperative tibial lateral condyle fractures after cementless Oxford UKA. Four patients underwent cementless Oxford UKA. Immediate postoperative radiography and CT showed no fracture lines. At five to six weeks postoperatively, MRI showed a fracture line from the intersection of the longitudinal and transverse tibial osteotomies through the lateral pinhole to the end of the lateral tibial diaphysis. At three months, bone union was observed without surgical treatments. Lateral tibial fracture after cementless Oxford UKA has a good clinical course without the need for surgical intervention. Medial fractures should thus be more actively prevented. MRI is useful for less symptomatic tibial lateral condyle fractures.

Prediction of Postoperative Range of Motion after Mobile-Bearing Medial Unicompartmental Knee Arthroplasty from the Preoperative Range of Motion and Other Preoperative Factors.

Postoperative flexion after unicompartmental knee arthroplasty might be predicted from the preoperative range of motion and other preoperative factors, but this has not been sufficiently investigated. Between 2013 and 2017, 198 patients (198 knees) underwent unilateral knee arthroplasty with medial mobile-bearing unicompartmental knee arthroplasty. Range of motion was measured preoperatively and at the time of final follow-up. To investigate the accuracy of the prediction of preoperative to postoperative gain or loss of the flexion angle, we performed receiver operating characteristic analysis. Logistic regression analysis was used to evaluate other predictive factors. Change in flexion angle was significantly strongly and negatively correlated with the preoperative flexion angle (R = - 0.688; 95% confidence interval: -0.755 to -0.607; p < 0.001). Preoperative flexion angle was suggested to be a significant predictor of gain or loss of the flexion angle with the area under the curve of 0.781; the cutoff value calculated using the Youden index was 140 degrees. Logistic regression analysis showed that in addition to the preoperative flexion angle of the operated side, the postoperative flexion range was significantly affected by the patient's height and by the preoperative flexion angle of the contralateral knee. If the preoperative flexion angle in Oxford mobile-bearing medial unicompartmental knee arthroplasty is <140 degrees, the postoperative flexion angle may be improved; if it exceeds 140 degrees, the postoperative flexion angle may worsen. This predictive ability is further improved by consideration of the patient's height and the range of motion on the contralateral side.

Caliper-Based Restricted Kinematic Alignment Total Knee Arthroplasty.

Restricted kinematic alignment total knee arthroplasty (rKA-TKA) is a reasonable selection for avoiding an extreme alignment that has been conceded to induce implant failure. However, computer-aided devices (CAS), such as navigation, robotics, and patient-specific instrumentation, are necessary to perform rKA-TKA. This paper reports on the surgical technique of kinematic alignment total knee arthroplasty (KA-TKA) using mechanical instruments. The lateral distal femoral angle (LDFA) and the medial proximal tibial angle (MPTA) are measured from preoperative long radiographs or CT of the lower limb, and the arithmetic hip-knee-ankle angle (aHKA) is calculated from the MPTA - LDFA. The predefined restriction boundaries are used to determine the osteotomy angle. In our practice, the LDFA is 85° to 93°, the MPTA is 85° to 90°, and the aHKA is 5° varus to 3° valgus. If correction of the femoral osteotomy is required, this can be achieved by changing the thickness of the paddle set on the distal articular surface or by adjusting the angle of the variable angle femoral cutting guide. For the tibia, the distal end of the extramedullary rod, with the proximal part placed in the center of the knee joint, should be adjusted so that it does not exceed the lateral malleolus. This limits the medial tilt of the osteotomy plane to within 5.5°. These techniques allow restricted KA to be performed with existing mechanical instruments without using CAS.

Varus placement of the tibial component reduces the potential risk of fracture with adequate bony coverage in the Oxford unicompartmental knee arthroplasty.

A short keel-cortex distance (KCD), especially to the posterior cortex, is a potential risk factor for tibial plateau fracture after Oxford mobile-bearing unicompartmental knee arthroplasty (OUKA). This study aimed to evaluate the effect of tibial component alignment in the coronal plane and tibial proximal morphology on the KCD. Included in this study were 51 patients scheduled for primary Oxford medial unicompartmental knee arthroplasty (UKA). The anterior and posterior KCD were preoperatively assessed using 3D simulation software with the component set perpendicular to the tibial mechanical axis (neutral), 3° valgus, 3° varus, and 6° varus, relative to neutral alignment. We evaluated the existence of overhanging medial tibial condyle where the medial eminence line, the line including the medial tibial eminence parallel to the tibial axis, passes outside of the tibial shaft. In all component alignments, patients with a medial overhanging condyle had significantly shorter posterior KCD than those without. In patients with a medial overhanging condyle, the posterior KCD significantly increased when the tibial component was placed in 3° varus (4.6 ± 1.5 mm, P = 0.003 vs neutral, P < 0.001 vs 3° valgus) and 6° varus (5.0 ± 1.4 mm, P < 0.001 vs neutral, P < 0.001 vs 3° valgus) compared with in neutral (3.5 ± 1.9 mm) or 3° valgus (2.8 ± 1.8 mm). In OUKA, varus implantation increased the KCD. This could potentially decrease the risk of fracture, even in knees with the overhanging medial condyle. Conversely, valgus implantation of the tibial component shortened the KCD, and should therefore be avoided.

The nascent polypeptide-associated complex subunit Egd1 is required for efficient selective mitochondrial degradation in budding yeast.

Selective degradation of dysfunctional or excess mitochondria is a fundamental process crucial for cell homeostasis in almost all eukaryotes. This process relies on autophagy, an intracellular self-eating system conserved from yeast to humans and is thus called mitophagy. Detailed mechanisms of mitophagy remain to be fully understood. Here we show that mitochondrial degradation in budding yeast, which requires the pro-mitophagic protein Atg32, is strongly reduced in cells lacking Egd1, a beta subunit of the nascent polypeptide-associated complex acting in cytosolic ribosome attachment and protein targeting to mitochondria. By contrast, loss of the sole alpha subunit Egd2 or the beta subunit paralogue Btt1 led to only a partial or slight reduction in mitophagy. We also found that phosphorylation of Atg32, a crucial step for priming mitophagy, is decreased in the absence of Egd1. Forced Atg32 hyperphosphorylation almost completely restored mitophagy in egd1-null cells. Together, we propose that Egd1 acts in Atg32 phosphorylation to facilitate mitophagy.

Public Health Centers' Training Session Programs to Develop Programs on Infection Control Practices for Multidrug-Resistant Organisms in Hospitals in Kawaguchi City, Japan.

Introduction The Kawaguchi City Public Health Center (PHC) conducted training sessions focusing on infection control practices on multidrug-resistant organisms (MDROs) for 19 hospitals and eight affiliated clinics (AFs) with beds in June 2022. Issues with infection control programs were identified via a survey implemented following the training sessions. These included providing feedback on infection control policies for MDROs, hand hygiene compliance programs (HHCPs), environmental cleaning (EC), and training sessions programs that hospitals or AFs with beds (hospitals) intended to implement in the future or develop (to be developed). We planned to examine whether the PHC training sessions programs have an effect on the development of hospital infection control programs designed to address these issues. The purpose of this study is to clarify the training session program provided by the Kawaguchi City PHC, which was effective in developing hospital infection control programs based on the results of the survey conducted after the training session. Methods In June 2023, a second training session that offered information on infection control practices was completed for 30 hospitals. This was followed by sending a questionnaire. We examined infection control programs to be developed and analyzed associations with the first learned information by training session (the first learned information). Results Twenty-four hospitals responded to the survey with a response rate of 80.0%. Half the respondents (12, 50.0%) had prepared for the infection control policy on carbapenem-resistant Enterobacteriaceae (CRE), 11 hospitals (45.8%) had provided feedback on HHC, and four (16.7%) planned to conduct feedback on HHC. HHCPs were planned to be developed by 19 hospitals (79.2%), EC by five hospitals (20.8%), training session by 12 hospitals (50.0%), and screening of MDROs upon hospital admission (AS) by nine hospitals (37.5%). The first learned information, "the prevention of healthcare-associated infections and cost savings by implementing cleaning bundles (the effects of cleaning bundles)," was identified by 10 hospitals (41.7%), and "specific programs on providing feedback effective for developing hand hygiene compliance (specific feedback)" was learned by eight hospitals (33.3%). The first learned information regarding specific feedback was significantly associated with HHCPs to be developed (p = 0.044). The first learned information on the effects of cleaning bundles was significantly associated with HHCPs and HHC feedback to be developed (p = 0.023, 0.034). The training session programs were not significantly connected to EC, training session, or AS to be developed. Conclusions Infection control programs to be developed were linked to the provision of information on numerical effects by implementing specific feedback and cleaning bundles. We suggest that the PHC should develop infection control programs for the hospitals and provide training sessions, including numerical effects.

Elevated stress response marks deeply quiescent reserve cells of gastric chief cells.

Gastrointestinal tract organs harbor reserve cells, which are endowed with cellular plasticity and regenerate functional units in response to tissue damage. However, whether the reserve cells in gastrointestinal tract exist as long-term quiescent cells remain incompletely understood. In the present study, we systematically examine H2b-GFP label-retaining cells and identify a long-term slow-cycling population in the gastric corpus but not in other gastrointestinal organs. The label-retaining cells, which reside near the basal layers of the corpus, comprise a subpopulation of chief cells. The identified quiescent cells exhibit induction of Atf4 and its target genes including Atf3, a marker of paligenosis, and activation of the unfolded protein response, but do not show elevated expression of Troy, Lgr5, or Mist. External damage to the gastric mucosa induced by indomethacin treatment triggers proliferation of the quiescent Atf4+ population, indicating that the gastric corpus harbors a specific cell population that is primed to facilitate stomach regeneration.

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.

The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain-containing ion transport regulator 3 (FXYD3), a component of the Na+/K+ pump. Accordingly, FXYD3+ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3+ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na+/K+ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.

Restricted Kinematically Aligned Total Knee Arthroplasty Following Failed Oxford Unicompartmental Knee Arthroplasty.

In this report, we describe how to revise a failed Oxford unicompartmental knee arthroplasty to kinematically aligned total knee arthroplasty (TKA). Its benefits are the maintenance of the native joint line along with the avoidance of supplemental parts, such as metal augments and stems. This can be applied to patients whose medial tibial cortex is well preserved. The distal cutting plane and rotation alignment are decided before the removal of the femoral component. The tibial cutting plane is up to 12 mm below the lateral joint surface and the varus is up to 5° below the extramedullary rod. Eventually, the native joint line and alignment along with the soft tissue envelope can be well maintained, similar to the restricted kinematically aligned TKA.