BACKGROUND: Recruitment and homing cells into graft materials from host tissue is crucial for bone regeneration. METHODS: Highly porous, multi-level structural, hydroxyapatite bone void filler (HA-BVF) have been investigated to restore critical size bone defects. The aim was to investigate a feasibility of bone regeneration of synthetic HA-BVF compared to commercial xenograft (Bio-Oss). HA-BVF of 0.7 mm in average diameter was prepared via template coating method. Groups of animals (n = 6) were divided into two with normal (Sham) or induced osteoporotic conditions (Ovx). Subsequently, subdivided into three treated with HA-BVF as an experiment or Bio-Oss as a positive control or no treatment as a negative control (defect). The new bone formation was analyzed by micro-CT and histology. RESULTS: At 4 weeks post-surgery, new bone formation was initiated from all groups. At 8 weeks post-surgery, new bone formation in the HA-BVF groups was greater than Bio-Oss groups. Extraordinarily greater bone regeneration within the Ovx-HA group than Sham-Bio-Oss or Ovx-Bio-Oss group (p<0.05). CONCLUSION: This study suggests that the immediate wicking property of HA-BVF from host tissue activates a natural healing cascade without the addition of exogeneous factors or progenitor cells. HA-BVF may be an effective alternative for repairing bone defects under both normal and osteoporotic bone conditions.
Animals ; Bone Regeneration* ; Capillary Action* ; Durapatite ; Heterografts ; Methods ; Models, Animal* ; Osteogenesis ; Osteoporosis ; Rats* ; Stem Cells ; Transplants*

Adipsia is a rare disorder that occurs due to damage to the osmoreceptor and not feeling thirst despite hyperosmolality. Adipsic hypernatremia can occur when there is damage to the anterior communicating artery that supplies blood to osmoreceptors, and the level of arginine vasopressin secretion varies widely. A 37-year-old woman, suffering from severe headache, was consulted to the nephrology department for hypernatremia and polyuria after clipping of a ruptured aneurysm in the anterior communicating artery. Despite her hypernatremic hyperosmolar state, she denied thirst and did not drink spontaneously. She was diagnosed adipsic hypernatremia by evaluating the osmoregulatory and baroregulatory function tests.Because adipsic hypernatremia is caused by not enough drinking water even for hyperosmolality due to the lack of thirst stimulus, the strategies of treatment are that setting the target body weight when serum osmolality is normal and have the patient drink water until patient reach the target body weight. Adipsic hypernatremia should be considered to be a rare complication of subarachnoid hemorrhage associated with an anterior communicating artery aneurysm.

PURPOSE: There is increasing epidemiological evidence of an association between childhood obesity and atopic dermatitis, but little is known about the underlying mechanism(s). In the present study, we used a rat model of atopic dermatitis to assess whether juvenile obesity, induced by reduction of litter size, aggravated the signs of atopic dermatitis and, if so, whether this aggravation was associated with changes in plasma concentration of adipokines, such as leptin and adiponectin. METHODS: Dermatitis was induced by neonatal capsaicin treatment. Body weight, dermatitis score, serum IgE, skin nerve growth factor (NGF), serum leptin and adiponectin, and cytokine mRNA expression in the skin lesion were compared between small (SL, 5 pups) and large litters (LL, 15 pups). RESULTS: The body weight of juvenile rats up to 6 weeks of age was significantly heavier in the SL group, compared with those in the LL group. The SL group showed more robust development of dermatitis, and higher levels of serum IgE and skin NGF than the LL group. Additionally, the SL group demonstrated higher levels of leptin and pro-inflammatory cytokine mRNA but lower levels of adiponectin than the LL group. CONCLUSIONS: These results suggest a causal link between a decrease in immunological tolerance, induced by juvenile obesity, and aggravation of atopic dermatitis.
Adipokines ; Adiponectin ; Animals ; Body Weight ; Capsaicin ; Dermatitis ; Dermatitis, Atopic* ; Immunoglobulin E ; Leptin ; Litter Size ; Models, Animal* ; Nerve Growth Factor ; Obesity* ; Pediatric Obesity ; Plasma ; Rats ; RNA, Messenger ; Skin

X-linked juvenile retinoschisis (XLRS) is characterized by the progressive loss of visual acuity and vitreous hemorrhage. XLRS is caused by a mutation of retinoschisin 1 (RS1) gene at Xp22.13. In the current report, a 2-year-old Korean patient with XLRS was described. The germline deletion of exon 1 was identified in the RS1 gene. Considering X-linked inheritance pattern, validation of a carrier state of a patient's mother is important for the genetic counseling of other family members and for the future reproductive plan. To confirm the carrier state of his mother, the multiplex ligation-dependent probe amplification analysis was done using peripheral leukocytes and found the heterozygous deletion of exon 1 in his mother.
Carrier State ; Child, Preschool ; Exons ; Genes, X-Linked ; Genetic Counseling ; Humans ; Leukocytes ; Mothers ; Multiplex Polymerase Chain Reaction ; Retinoschisis* ; Visual Acuity ; Vitreous Hemorrhage

PURPOSE: We have summarized the experience of our institution related to what treatment has been performed in patients with pancreatic fistula and their outcome.METHODS: Seventy-eight pancreatico-enteric anastomosis failure (PEAF) patients of 403 pancreaticoduodenectomy (PD) were included for this retrospective study. PEAF was defined by the presence of rich amylase (over 10,000 IU/L) in drainage fluid at postoperative day 5 to 7 and radiographic demonstration of the anastomotic breakdown and associated local fluid collection. The management was analyzed by observation group (O group), intervention (I group) and surgery group (S group).RESULTS: Preoperative clinical status of the PEAF group and non-PEAF group was similar. Bile duct cancer was the highest risk subgroup of the PEAF (P=0.001) and the pancreatic adenocarcinoma showed the least risk for the PEAF (P<0.001). Among the 78 PEAF patients, 50 were managed as a conservative treatment, 15 patients were received radiologic intervention and 13 patients performed rescue surgery. Among these three subgroups, there was no statistical significance in the patient's demographics, clinical status, surgical factors and disease nature. However, mortality was significantly higher in the S group (P<0.001). The mortality cases were developed one and six patients in O and S group, respectively. Surgical procedures in S group were completion total pancreatectomy with or without splenectomy (n=12) and pancreatectomy preserving spleen in four (28.6%). Pancreaticogastrostomy repair and Roux-en-Y pancreaticojejunostomy reconstruction were performed each case, respectively.CONCLUSION: Proper drainage catheter indwelling during the PD or postoperative radiological intervention can effectively manage the PEAF without surgical interventional treatment.
Adenocarcinoma ; Amylases ; Bile Duct Neoplasms ; Catheters ; Demography ; Drainage ; Humans ; Mortality ; Pancreatectomy ; Pancreatic Fistula ; Pancreaticoduodenectomy ; Pancreaticojejunostomy ; Retrospective Studies ; Spleen ; Splenectomy

Background: This nationwide study aimed to investigate the blood transfusion status of elderly hip fracture patients and to examine the effect of packed red blood cell transfusion on all-cause mortality. Methods: From the Korean National Health Insurance Service-Senior cohort consisting of 588,147 participants aged over 60 years in 2002, a total of 14,744 new-onset hip fracture patients aged 65–99 years were followed up for 11 years. The adjusted hazard ratios (aHRs), risk ratios, and their 95% confidence intervals were estimated by the Cox proportional hazard model and Poisson regression model. Results: There were 10,973 patients (74.42%) in the transfusion group and 3,771 (25.58%) patients in the non-transfusion group. The mean volume of blood transfusion was 1,164.51 mL (± 865.25; median, 800 mL; interquartile range, 640–1,440). In the multivariable-adjusted Cox proportional hazard model, the transfusion group had 1.34-fold more risk of all-cause mortality than the non-transfusion group (aHR, 1.34; 95% confidence interval [CI], 1.26–1.42). In the multivariate-adjusted Poisson regression model, hip fracture patients in the transfusion group were 1.43 (adjusted risk ratio [aRR], 1.43; 95% CI, 1.09–1.87; p = 0.009) folds more likely to die within 30 days than those in the non-transfusion group. The mortality risk was highest at 90 days (aRR, 1.64; 95% CI, 1.40–1.93; p < 0.001) and slightly decreased at 180 days (aRR, 1.58;95% CI, 1.40–1.79; p < 0.001) and 1 year (aRR, 1.43; 95% CI, 1.31–1.58; p < 0.001). Conclusion In this nationwide representative cohort study, blood transfusion was performed in 75% of hip fracture patients. Even after adjusting for comorbidity and anticoagulant use, the postoperative results (hospitalization, mortality) of the transfusion group did not show significantly worse results than the non-transfusion group. Therefore, adequate patient blood management can only improve the patient's outcome after hip fracture surgery.

Staphylococcus aureus (S. aureus ) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S.aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ+/IL-4+ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V+/7-AAD+ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163+ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.