Effect of protopanaxadiol derivatives in high glucose-induced fibronectin expression in primary cultured rat mesangial cells: Role of mitogen-activated protein kinases and Akt

A lot of anti-diabetic agents using natural plants have been extensively studied. Ginsenosides are known to be used as a remedy for diabetes in Asian countries and American Societies. Diabetic nephropathy is a major complication of diabetes mellitus. Extracellular matrix in mesangial cells is mainly composed of fibronectin and the increase of fibronectin is a hallmark of diabetic nephropathy. Protopenaxadiol (PPD) is a major component of total ginseng. Thus, we examined the regulatory mechanism of PPD derivatives-induced preventive effect of fibronectin expression in mesangial cells cultivated under diabetic condition. In present study, ginsenoside Rb1 prevented the high glucose-induced increase of fibronectin expression in mesangial cells. Ginsenoside Rb2 and Rg3 also mildly inhibited it. However, ginsenoside Rc and Rd did not prevent the high glucose-induced increase of fibronectin expression in mesangial cells. In addition, ginsenoside Rb1 prevented high glucose-induced phosphorylation of p44/42 mitogen activated protein kinase (MAPK), p38 MAPK, JNK/SAPK, and Akt. These results suggest that ginsenoside Rb1 is the most powerful component of PPD derivatives. In conclusion, ginsenoside Rb1 prevented high glucose-induced increase of fibronectin expression via the inhibition of MAPK-Akt signaling cascade.     

Debate on annual influenza vaccination in healthcare workers for the same subtype under the vaccine shortage.

BACKGROUND: Influenza vaccination is the primary method for preventing influenza and its severe complications. Healthcare workers (HCWs) are one of the priority groups for the influenza vaccination. OBJECTIVES: To determine whether healthy HCWs, who were vaccinated with the same subtype for the two previous years, could be given less priority for influenza immunization under the vaccine shortage. STUDY DESIGN: We measured hemagglutination-inhibition antibody titers from sequential serum samples in 50 pre-immune subjects and 50 age-matched vaccine-naive subjects: immediately prior to the administration of the vaccine, 4-6 weeks, and 6 months after the vaccination. RESULTS: Prevaccination titers were maintained above protective level and high protection rates were observed for all three strains in pre-immune subjects: A/H1N1, A/H3N2, and B strains. As for the sequential changes, the protection rates for all three strains still remained above 70% until 6 months following the vaccination. CONCLUSION: Skipping influenza vaccination for a year could be considered in healthy pre-immune HCWs under the epidemic of the same subtype as two previous years.     

Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.     

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02165878","term_id":"NCT02165878"}}NCT02165878     

Developing a Framework for Pandemic COVID-19 Vaccine Allocation: a Modified Delphi Consensus Study in Korea

BackgroundThis study presents a framework for determining the allocation and distribution of the limited amount of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsAfter analyzing the pandemic strategies of the major organizations and countries and with a literature review conducted by a core panel, a modified Delphi survey was administered to 13 experts in the fields of vaccination, infectious disease, and public health in the Republic of Korea. The following topics were discussed: 1) identifying the objectives of the vaccination strategy, 2) identifying allocation criteria, and 3) establishing a step-by-step vaccination framework and prioritization strategy based on the allocation criteria. Two rounds of surveys were conducted for each topic, with a structured questionnaire provided via e-mail in the first round. After analyzing the responses, a meeting with the experts was held to obtain consensus on how to prioritize the population groups.ResultsThe first objective of the vaccination strategy was maintenance of the integrity of the healthcare system and critical infrastructure, followed by reduction of morbidity and mortality and reduction of community transmission. In the initial phase, older adult residents in care homes, high-risk health and social care workers, and personal support workers who work in direct contact with coronavirus disease 2019 (COVID-19) patients would be prioritized. Expansion of vaccine supply would allow immunization of older adults not included in phase 1, followed by healthcare workers not previously included and individuals with comorbidities. Further widespread vaccine supply would ensure availability to the extended adult age groups (50–64 years old), critical workers outside the health sector, residents who cannot socially distance, and, eventually, the remaining populations.ConclusionThis survey provides the much needed insight into the decision-making process for vaccine allocation at the national level. However, flexibility in adapting to strategies will be essential, as new information is constantly emerging.     

Pediatric Femoral Shaft Fracture: An Age-Based Treatment Algorithm

PurposeFractures of the femoral shaft in children are common. The rates of bone growth and remodeling in children vary according to their ages, which affect their respective management. MethodsThis paper evaluates the incidence and patterns of pediatric femoral shaft fracture and the current concepts of treatments available.ResultsThe type of fracture—closed or open; stable or unstable—needs to be taken into account. Child abuse should be suspected in fractures sustained by infants. For younger children, non-surgical management is preferred, which include Pavlik harness (< 6 months old) and early spica casting (6 months to 6 years old). Older children (> 6 years old) usually benefit from surgical treatments as outcomes of non-surgical alternatives are worse and are associated with prolonged recovery times. These operative measures for older children that are 6–12 years old include elastic stable intramedullary nailing and submuscular plating. Factors to be considered when devising an appropriate intervention include body mass, location of injury, and nature of fracture. For adolescent and skeletally mature teenagers (> 12 years old), rigid antegrade entry intramedullary fixation is indicated. In the event of open fractures or polytrauma, external fixation should be considered as a temporary treatment method for initial fracture stabilization.ConclusionAn age-based and evidence-based algorithm has been proposed to guide surgeons in the process of evaluating an appropriate treatment.     

From skin allograft coverage to allograft–micrograft sandwich method: A retrospective review of severe burn patients who received conjunctive application of cultured epithelial autografts

A 12-year retrospective review of severe burn patients who received cultured epithelial autografts (CEA) at the Singapore General Hospital Burns Centre from January 2005 to December 2016 was carried out. During this period, two different surgical modalities were employed to manage these burn injuries. In the earlier period, following early excision of the burn wounds, exposed surfaces were covered with a combination of split thickness skin autografts (STSG) and allografts. Surfaces covered with skin allografts were subsequently debrided of the allo-epidermis in about 3 weeks later, exposing the allodermis with granulating tissues for grafting of CEA; a technique known as the Cuono’s method. In the later period, allograft–autologous micrograft sandwich technique was used to graft on the early excised burns with subsequent CEA grafting. The former and latter groups represented by STSG/C (n = 10) and M/CEA (n = 14) respectively, were compared in terms of clinical profiles, outcomes, allograft/CEA usage and total graft cost. No significant differences were found based on mean age and presence of inhalation burns between the two treatment methods However, percentage total body surface area (TBSA) and Revised Baux Score were significantly higher (p < 0.05) in the M/CEA group compared to the STSG/C group. Differences in clinical outcomes of mortality and length of hospital stay between the 2 groups were statistically insignificant. The average area amount of skin allografts used per patient in the M/CEA group was significantly lower compared to the STSG/C method group which contributed to lower total average cost of grafts used per % TBSA in the M/CEA method group. This might be attributed to the presence of micrografts which seemed to improve stabilization of the wound bed resulting in less operating procedures and improving CEA take. To conclude, the M/CEA method introduced was able to treat more severe burn patients at lower graft costs without compromising critical clinical outcomes significantly.     

Tactile assessment for the reversibility of rocuronium-induced neuromuscular blockade during propofol or sevoflurane anesthesia

We sought to determine whether tactile train-of-four (TOF) count can predict the efficacy of neostigmine administration for rocuronium-induced blockade during propofol or sevoflurane anesthesia, and to follow subsequent recovery until the TOF ratio reached 0.9. One-hundred-sixty patients, divided into eight equal groups, were randomly allocated to maintenance of anesthesia with propofol or sevoflurane. The tactile response of the adductor pollicis to TOF stimulation was evaluated on one arm, and the mechanomyographic response was recorded on the other. Neuromuscular block was induced with rocuronium 0.6 mg/kg and maintained with rocuronium to 15% of the control first twitch in TOF. Neostigmine 0.07 mg/kg was administered on reappearance of the first (Group I), second (Group II), third (Group III), or fourth (Group IV) tactile TOF response in each anesthesia. At this time, sevoflurane or the propofol dosage was reduced in each group (n = 20 in each group). The times from administration of neostigmine until the TOF ratio recovered to 0.7, 0.8, and 0.9 were recorded. The times [median (range)] to TOF ratio = 0.9 were 8.6 (4.7-18.9), 7.5 (3.4-9.8), 5.4 (1.6-8.6), and 4.7 (1.3-7.2) min in Groups I-IV during propofol anesthesia, respectively, and 28.6 (8.8-75.8), 22.6 (8.3-57.4), 15.6 (7.3-43.9), and 9.7 (5.1-26.4) min in corresponding groups during sevoflurane anesthesia, respectively (P < 0.0001). We recommend more than 2 TOF responses with propofol anesthesia and 4 TOF responses with sevoflurane anesthesia for adequate reversal within 10 and 15 min, respectively. The more tactile TOF responses present at the time of reversal achieved greater adequate recovery; however, tactile TOF responses are not a completely reliable predictor within a reasonable time period.