The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.

Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria.

In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery.

S100A9 and EGFR gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy.

BACKGROUND: In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. PATIENTS AND METHODS: Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. RESULTS: Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. CONCLUSIONS: The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.

Forced collapse of the blastocoel cavity improves developmental potential in cryopreserved bovine blastocysts by slow-rate freezing and vitrification.

This study was conducted to evaluate the effectiveness of forced collapse of the blastocoel before slow-rate freezing and vitrification of bovine blastocysts. Cryopreservation of bovine blastocysts has been proposed as a tool to improve the feasibility of cattle production using the embryo transfer technique. However, the low efficiency of frozen-thawed embryos survival and further development is a crucial problem. In this study, bovine in vitro and in vivo blastocysts were slow-rate frozen and vitrified after forced blastocoele collapse (FBC) of the blastocyst cavity by puncturing the blastocoele with a pulled Pasteur pipet. Differences in the developmental potential of frozen-thawed blastocysts derived from FBC and non-FBC groups were found in both slow-rate freezing and vitrification. Furthermore, we found that the total cell number of blastocysts in FBC groups was increased and the index of apoptosis in FBC groups was decreased. Consistent with these results, real-time RT-PCR analysis data showed that expression of the anti-apoptotic Bcl-XL gene was significantly increased by FBC groups, whereas expression of the pro-apoptotic Bax gene was significantly decreased by FBC groups. Our results also showed that pregnancy outcomes in both slow-rate frozen and vitrified bovine in vivo blastocysts could be improved by reducing the fluid content after FBC of the blastocyst cavity. Therefore, we suggest that FBC of the blastocyst cavity with a pulled Pasteur pipet is an effective pre-treatment technique for both slow-rate freezing and vitrification of bovine blastocysts.

Models of Care for Postacute COVID-19 Clinics: Experiences and a Practical Framework for Outpatient Physiatry Settings.

ABSTRACT: After surviving infection with the SARS-CoV-2 virus, individuals may have persistent symptoms and prolonged impairments that may last for weeks to months. The frequency and heterogeneity of persistent post-COVID conditions have created challenges in care. Specialty clinics are being established in response to an increasing need to care for patients with postacute sequelae of SARS-CoV-2 or long COVID syndrome. Although many post-COVID conditions can be bettered through a comprehensive rehabilitation plan, various clinical settings may benefit from differing models of coordinated care. We present five models of care in varying degrees of development and compare processes and adaptations to address the unique needs of each center and their unique patient populations. Forging a path to recovery will necessitate a multidisciplinary team with physiatry involvement to meet the distinctive needs of patients with postacute sequelae of SARS-CoV-2. Furthermore, it is imperative that there be equitable access to this care and commitment from healthcare institutions to provide resources for these programs.

Ultrastructural changes in platelet activating factor-induced epithelial damage in rabbit maxillary sinus mucosa.

Platelet activating factor (PAF), a potent chemical mediator in inflammation and allergic reaction, has been thought to induce mucociliary inhibition and epithelial damage in the airway mucosa. However, several recent papers have reported that PAF may not readily damage the airway epithelium. The aim of this study was to elucidate the pathogenesis of PAF-induced epithelial damage in terms of ultrastructural changes. Sixteen micrograms of PAF (1 mL of 16 microg/mL) was administered into the maxillary sinuses of rabbits. The rabbits were divided into 2 groups according to time intervals, and the antral mucosa was taken 1 and 3 days after administration of PAF. The tissue was processed for routine transmission electron microscopy. No epithelial degeneration was observed other than platelet aggregation, red blood cell stasis, and swelling of the endothelial cells 1 day after administration of PAF. Migration of inflammatory cells into the perivascular connective tissue, infiltration of eosinophils into the subepithelial and intraepithelial spaces, and vacuolar degeneration of the epithelial cells with focal loss of cilia were seen 3 days after administration of PAF. In conclusion, PAF induced infiltration of eosinophils into the epithelium, and resulted in epithelial degeneration that varied according to the time interval. Our findings suggest that PAF may cause epithelial damage through a series of secondary events, probably due to cytotoxicity of eosinophils infiltrating the epithelium.

Effect of platelet activating factor and its antagonist on the mucociliary clearance of the eustachian tube in guinea pigs.

The purpose of this study was to test whether platelet activating factor (PAF) impairs the mucociliary clearance function of the eustachian tube (ET) in a dose-dependent manner and whether PAF antagonist can prevent the impairment of mucociliary function of the ET induced by PAF. Coomassie brilliant blue dye transport time (DTT) in normal guinea pigs was 69 seconds. The DTTs after the application of normal saline and PAF at I and 2 microg/mL into bullae were 66, 74, and 157 seconds. The time was over 15 minutes when 4, 8, and 16 microg/mL of PAF were applied. The DTT was 62 seconds when the animals were pretreated with PAF antagonist (WEB 2170). There were significant delays of the DTTs after treatment with 2, 4, 8, and 16 microg/mL of PAF. Histopathologic examination of ETs from groups with a significant delay in DTTs showed intact cilia, mucous plugs, increased inflammatory cells, and exfoliation of cells. This study demonstrated that PAF impaired the mucociliary clearance function of the ET in a dose-dependent manner. This impairment of mucociliary clearance function was prevented by pretreatment with PAF antagonist. The findings of the study suggest that PAF plays an important role in the pathogenesis of otitis media with effusion by impairing the ET clearance function.

RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: potential role in the prediction of tumor progression.

PURPOSE: Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RESULTS: RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression. CONCLUSIONS: RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR.

Effects of germination and osmopriming treatment on enhancement of isoflavone contents in various soybean cultivars and cheonggukjang (fermented unsalted soybean paste).

To develop soybean products containing high isoflavone contents, the effects of germination and osmopriming on the isoflavone contents of 3 soybean cultivars (Ilmi, Daehwang, and Taekwang) were investigated. Total isoflavone contents of Ilmi and Daehwang cultivars were not significantly different with soaking time at 20 and 25 degrees C. Ilmi and Taekwang cultivars had higher total isoflavone contents at 0.243 to 0.256 and 0.072 to 0.079 g/100 g, respectively, after 12 h of germination at 20 degrees C than those at 0.232 and 0.064 g/100 g at the initial stage. After 48 h of germination at 20 degrees C, contents of total isoflavone, daidzein, and genistein were 0.246, 0.094, and 0.147 g/100 g, respectively. In contrast, after 48 h of germination and 0.2 M NaCl treatment at 20 degrees C, those contents increased up to 0.346, 0.140, and 0.203 g/100 g, respectively. Total isoflavone and genistein contents of cheonggukjang prepared with germinated soybean or soybeans treated with osmopriming were 0.322 and 0.198 g/100 g, 0.332 and 0.201 g/100 g, respectively, at 48 h of fermentation, and were higher than those of the control group (0.277 and 0.169 g/100 g). We concluded that cheonggukjang would contain higher isoflavone contents after the treatment of germination and osmopriming.

Solution structure of a designed amphipathic antimicrobial synthetic peptide, PGAa.

A designed peptide, PGAa showed an excellent antifungal activity as well as an efficient bactericidal activity toward gram-positive, especially in the pathogenic yeast Candida albicans 28838. The solution structures of PGAa have been determined both in 40% TFE/water solution and DPC micelle by CD and NMR spectroscopy. Based on NOEs, vicinal coupling constants, backbone amide exchange rates, and chemical shift indices, PGAa formed a long amphipathic alpha-helical conformation in both TFE and DPC micelle environments, spanning the residues Ile(2)-Ala(19) in TFE and Lys(5)-Ala(19) in DPC micelle, respectively. Solution structures suggested that the hydrophobic residues would interact with the fatty acyl chains of the lipid bilayer, while the positively charged side-chains exposed to aqueous environments. Therefore, we conclude that the alpha-helical structure as well as the highly amphiphatic nature of PGAa peptide may play a critical role in its antimicrobial activity as well as selectivities in different species.

HWY-289, a novel semi-synthetic protoberberine derivative with multiple target sites in Candida albicans.

The antifungal properties of 515 synthetic and semi-synthetic protoberberines were investigated. HWY-289 was chosen for further study because it exhibited the most significant anti-Candida activity (MICs were 1.56 mg/L for Candida albicans and Candida krusei; 6.25 mg/L for Candida guilliermondii) but did not demonstrate toxicity in rats. HWY-289 inhibited the incorporation of L-[methyl-(14)C]methionine into the C-24 of ergosterol in whole cells of C. albicans (IC(50) 20 microM). However, HWY-289 (100 microM) had no effect on mammalian cholesterol biosynthesis in rat microsomes while miconazole (100 microM) was a potent inhibitor of cholesterol biosynthesis under identical assay conditions. A second major target site for HWY-289 was identified that involves cell wall biosynthesis in C. albicans. HWY-289 was a potent inhibitor of the chitin synthase isozymes CaCHS1 and CaCHS2, with IC(50) values of 22 microM for each enzyme. The effect was highly specific in that HWY-289 had no significant effect on C. albicans CaCHS3 (IC(50) > 200 microM). Thus, HWY-289 compared favourably with well-established antifungal agents as an inhibitor of the growth of Candida species in vitro, and may have considerable potential as a new class of antifungal agent that lacks toxic side effects in the human host.