Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception.

A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the "gain-of-editing" variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the "loss-of-editing" (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors-both Unc80 deficient (Unc80+/-) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80's neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity.

Pathogenicity and Genomic Characterization of a Novel Genospecies, Bacillus shihchuchen, of the Bacillus cereus Group Isolated from Chinese Softshell Turtle (Pelodiscus sinensis).

The Chinese softshell turtle (CST; Pelodiscus sinensis) is a freshwater aquaculture species of substantial economic importance that is commercially farmed across Asia, particularly in Taiwan. Although diseases caused by the Bacillus cereus group (Bcg) pose a major threat to commercial CST farming systems, information regarding its pathogenicity and genome remains limited. Here, we investigated the pathogenicity of Bcg strains isolated in a previous study and performed whole-genome sequencing. Pathogenicity analysis indicated that QF108-045 isolated from CSTs caused the highest mortality rate, and whole-genome sequencing revealed that it was an independent group distinct from other known Bcg genospecies. The average nucleotide identity compared to other known Bcg genospecies was below 95%, suggesting that QF108-045 belongs to a new genospecies, which we named Bacillus shihchuchen. Furthermore, genes annotation revealed the presence of anthrax toxins, such as edema factor and protective antigen, in QF108-045. Therefore, the biovar anthracis was assigned, and the full name of QF108-045 was Bacillus shihchuchen biovar anthracis. In addition to possessing multiple drug-resistant genes, QF108-045 demonstrated resistance to various types of antibiotics, including penicillins (amoxicillin and ampicillin), cephalosporins (ceftifour, cephalexin, and cephazolin), and polypeptides, such as vancomycin.

Comprehensive functional genomic analyses link APC somatic mutation and mRNA-miRNA networks to the clinical outcome of stage-III colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is a major health concern globally, but exhibits regional and/or environmental distinctions in terms of outcome especially for patients with stage III CRC. METHODS: From 2014 to 2016, matched pairs of tumor and adjacent normal tissue samples from 60 patients with stage I-IV CRC from Chang Gung Memorial Hospital in Taiwan were analyzed using next-generation sequencing. The DNA, mRNA, and miRNA sequences of paired tumor tissues were profiled. An observational study with survival analysis was done. Online datasets of The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) were also integrated and compared. RESULTS: The gene that exhibited the highest mutation rate was adenomatous polyposis coli (APC) (75.0%), followed by TP53 (70.0%), KRAS (56.6%), and TTN (48.3%). APC was also the most frequently mutated gene in TCGA and ICGC datasets. Surprisingly, for non-metastatic cases (stages I-III), CRC patients with mutated APC had better outcome in terms of overall survival (p = 0.041) and recurrence free survival (p = 0.0048). Particularly for stage III CRC, the overall survival rate was 94.4% and 67.7%, respectively (p = 0.018), and the recurrence free survival rate was 94.4% and 16.7%, respectively (p = 0.00044). Further clinical and gene expression analyses revealed that the APC wt specimens to a greater extent exhibit poor differentiation state as well as EGFR upregulation, providing molecular basis for the poor prognosis of these patients. Finally, based on integrated transcriptome analysis, we constructed the mRNA-miRNA networks underlying disease recurrence of the stage III CRC and uncovered potential therapeutic targets for this clinical condition. CONCLUSION: For stage III CRC, patients with mutated APC had better overall and recurrence free survival.

Dissociation of polyethylene insert from the tibial baseplate following revision total knee arthroplasty.

Dissociation of a modular tibial insert from the metal baseplate is a rare complication after revision total knee arthroplasty. We herein report an unusual presentation of a polyethylene insert failure that occurred in a posterior-stabilized constrained total knee arthroplasty. The polyethylene insert was posteriorly displaced, which has never been reported in the literature. The assumed mechanism is disengagement of the locking screw after repetitive motion. During knee full extension while standing from a chair, a sudden downward force on the anterior half of the insert caused posterior lift-off of the insert from the tibial baseplate and promoted a sliding force to push the insert posterior when the locking mechanism failed. This unique complication in a fully constrained posterior-stabilized implant should be considered as a cause for implant failure.

Treatment of diabetic foot infection with hyperbaric oxygen therapy.

BACKGROUND: This study was performed to evaluate the effectiveness of hyperbaric oxygen therapy (HBOT) in the treatment of the infected diabetic foot. METHODS: Forty-two patients with 44 infected diabetic feet receiving HBOT were divided into two groups. One group of 21 patients with 21 feet received <10 sessions of HBOT. The other 21 patients with 23 feet received >10 sessions of HBOT. RESULTS: In patients who received <10 sessions of HBOT, seven patients achieved satisfactory wound healing. Feet were preserved in 33.3%. In patients with >10 sessions of HBOT, 16 patients with 18 feet achieved good wound healing. Of these patients, 78.3% preserved their feet. This group of patients received an average of 22.8 HBOT treatments. CONCLUSIONS: Adjunctive HBOT has a positive effect on wound healing in diabetic foot with infection. The effect of HBOT seems dose dependent because the amputation rate is decreased in patients who receive adequate HBOT.

Anterior-inferior plating of middle-third fractures of the clavicle.

INTRODUCTION: Various techniques have been reported for the treatment of middle-third clavicle (collar bone) fractures. This prospective study was conducted to evaluate the results of anterior-inferior plating using a 3.5-mm reconstruction plate for the treatment of middle-third clavicle fractures. PATIENTS AND METHODS: Twenty-six patients with middle-third clavicle fractures were treated with anterior-inferior plating. The indications for surgery included complete displacement, severe comminution, and marked shortening of the clavicle (>2 cm). RESULTS: The mean time to union was 14 weeks (range 8-20 weeks). At the time of latest follow-up, all of the patients had returned to their pre-injury activity level. The plates were removed in ten patients after the fractures healed. No patients required plate removal due to implant-related problems. CONCLUSION: Anterior-inferior plating is an effective treatment modality for middle-third clavicle fractures, with few complications and early return of shoulder function. The procedure provides stable fixation, avoids risk to vital structures below the clavicle, and is associated with a low rate of implant-prominence problems.

Management of nonunion associated with broken intramedullary nail of the femur.

This study analyzed 14 patients with 17 broken intramedullary nails for the treatment of femoral fractures. Average distance from the fracture site was 7.9 cm in cases in which nail breakage occurred at the junction between the cylindrical and cloverleaf portions and 6.4 cm in cases in which nail breakage occurred at the screw hole. Eleven patients with 14 broken nails were treated with exchange nailing and bone grafting, 2 were treated with plating and bone grafting, and 1 was treated with extracorporeal shock wave therapy. Nonunion or delayed union is the main cause of nail breakage. Exchange nailing with bone grafting is a safe and effective method of treatment for a broken intramedullary nail with nonunion.

Surgical treatment of fractures of the greater trochanter associated with osteolytic lesions. Surgical technique.

BACKGROUND: A fracture of the greater trochanter through an osteolytic lesion may occur as a late complication after total hip arthroplasty. The optimal treatment for this difficult complication remains controversial. We have treated this problem with internal fixation and allogeneic bone-grafting at the time of revision of a loose acetabular component. METHODS: We retrospectively reviewed the results of treatment of a fracture through an osteolytic lesion of the greater trochanter in nineteen patients seen from 1996 to 2002. All fractures were treated with morselized allogeneic bone grafts and wire fixation at the time of revision of a failed acetabular component. Postoperative care included the use of an abduction orthosis and protected weight-bearing for at least three months. Follow-up of all patients consisted of radiographic examinations and clinical evaluation with use of the Harris hip score. RESULTS: At an average duration of 3.8 years after the revision, eighteen of the nineteen fractures had healed. The average time to healing was five months. The one treatment failure occurred in a patient who did not comply with the use of an abduction orthosis. The average Harris hip score for all patients improved from 32.5 points preoperatively to 91.2 points at the time of the latest follow-up. Polyethylene wear and recurrent osteolysis of the greater trochanter was noted in one hip at the eight-year follow-up examination. CONCLUSIONS: Fractures of the greater trochanter associated with osteolytic lesions can be effectively treated with open reduction, internal fixation with wire, and allogeneic bone-grafting.

Pathogenesis of partial tear of the rotator cuff: a clinical and pathologic study.

This prospective study investigated the clinical and pathologic results in 66 patients with partial tears of the rotator cuff from January 1996 to December 1998. The pathologic change in the rotator cuff was graded from the magnetic resonance images by using the criteria described by Zlatkin and Iannotti. A modified grading system from Ozaki and Panni was used for pathologic grading of the anterior acromion. The functional score of Constant and Murley was used for clinical assessment. The pathologic change in the rotator cuff revealed by the magnetic resonance imaging study was more severe in patients with articular side tears compared with patients who had bursal side tears. On the contrary, the pathologic changes in the acromion were significantly milder in patients with articular side tears compared with bursal side tears. These observations indicate that articular side tears of the rotator cuff are mainly associated with intrinsic pathologic changes of the rotator cuff, whereas bursal side tears are associated with subacromial impingement on an underlying milder pathologic change of the rotator cuff.

Surgical treatment of fractures of the greater trochanter associated with osteolytic lesions.

BACKGROUND: A fracture of the greater trochanter through an osteolytic lesion may occur as a late complication after total hip arthroplasty. The optimal treatment for this difficult complication remains controversial. We have treated this problem with internal fixation and allogeneic bone-grafting at the time of revision of a loose acetabular component. METHODS: We retrospectively reviewed the results of treatment of a fracture through an osteolytic lesion of the greater trochanter in nineteen patients seen from 1996 to 2002. All fractures were treated with morselized allogeneic bone grafts and wire fixation at the time of revision of a failed acetabular component. Postoperative care included the use of an abduction orthosis and protected weight-bearing for at least three months. Follow-up of all patients consisted of radiographic examinations and clinical evaluation with use of the Harris hip score. RESULTS: At an average duration of 3.8 years after the revision, eighteen of the nineteen fractures had healed. The average time to healing was five months. The one treatment failure occurred in a patient who did not comply with the use of an abduction orthosis. The average Harris hip score for all patients improved from 32.5 points preoperatively to 91.2 points at the time of the latest follow-up. Polyethylene wear and recurrent osteolysis of the greater trochanter was noted in one hip at the eight-year follow-up examination. CONCLUSIONS: Fractures of the greater trochanter associated with osteolytic lesions can be effectively treated with open reduction, internal fixation with wire, and allogeneic bone-grafting.

Results of vancomycin-impregnated cancellous bone grafting for infected tibial nonunion.

INTRODUCTION: Bone grafting plays a critical role in promoting bone healing in infected nonunion, although recurrent infection is of concern. Cancellous bone grafting as an antibiotic delivery system has been reported as an effective method to combat infections. In this study, we report the clinical results of vancomycin-impregnated cancellous bone grafting for the treatment of infected tibial nonunion. MATERIALS AND METHODS: Between January 1996 and March 2001, 18 patients with infected tibial nonunion treated with vancomycin-impregnated cancellous bone grafting were available for follow-up. According to the Cierny-Mader classification, all patients belonged to type IVA and IVB osteomyelitis. Adequate debridement, stabilization with external fixation, and staged vancomycin-impregnated cancellous bone grafting were used in all patients. Regular clinical and radiographic follow-ups were conducted. RESULTS: Infection control was obtained in all 18 patients with a 100% infection arrest rate. Bone union was achieved in 13 of 18 patients at an average of 5.8 months. Bone union was obtained subsequently in the remaining five patients after closed nailing in four, and plating and bone grafting in one patient. Radiographs showed good consolidation and hypertrophy of grafted bone at an average follow-up of 48 months. CONCLUSION: We conclude that vancomycin-impregnated cancellous bone grafting is a safe method for the treatment of infected tibial nonunion.

Femoral head preservation in non-united femoral neck fracture and head osteonecrosis in Cushing's disease.

There have been few reports associating avascular necrosis of bone with Cushing's disease. Patients with Cushing's disease and avascular necrosis of the femoral head usually receive total hip arthroplasty. However, hip prosthetic replacement in younger patients has been criticized due to a high incidence of component loosening. We report a case of successful femoral head preservation in non-united femoral neck fracture and head osteonecrosis in a 14-year-old girl with Cushing's disease (adrenocorticotropic hormone-secreting pituitary adenoma) who developed avascular necrosis of the right femoral head and pathologic fracture of the right femoral neck 2 years after the onset of hypercortisolism. Subtrochanteric valgus osteotomy was performed to preserve the femoral head after successful transsphenoidal surgery to remove pituitary microadenoma. At follow-up 10 years after the osteotomy, the femoral head had revascularized and the femoral neck fracture were united with much improvement of hip function. Dual energy X-ray absorptiometry scan of the right hip showed +0.86 SD from the normal bone densitometry. Aggressive femoral head preservation may be an effective alternative to treat this rare situation in a teenager.

Results of curettage and high-speed burring for chondroblastoma of the bone.

BACKGROUND: Chondroblastomas of the bone are rare lesions. Most of these lesions can be successfully treated by curettage and bone grafting. However, a considerable rate of recurrence has been reported, especially in aggressive lesions. The purpose of this study was to report the results of 10 cases of chondroblastomas of the bone treated with curettage and high-speed burring. METHODS: Ten patients with histologically confirmed chondroblastoma of the bone were treated with curettage and high-speed burring between October 1991 and August 2000. There were 7 men and 3 women with an average age of 18.9 (range, 12 to 30) years. Radiographically, 3 were classified as having aggressive lesions, and 7 were classified as having non-aggressive ones. For treatment, 8 of them had defects packed with either bone grafts or bone substitutes; 1 defect was packed with bone cement; and the other was left alone because the lesion was small. RESULTS: At an average follow-up period of 62 (range, 8 to 112) months, all patients had painless, normal function of the affected limb without local recurrence or distant metastasis. Complete healing of the lesion was seen in 8 patients including the one without a bone graft. The lesion in 1 patient who had received bone cement remained unchanged radiographically. One patient experienced incomplete healing of the lesion, which was caused by inadequate packing of the bone substitute. CONCLUSION: Curettage and high-speed burring represent an effective method for the treatment of chondroblastoma of the bone whether in the non-aggressive or aggressive stage.