Gene-based association tests in family samples using GWAS summary statistics.

Genome-wide association studies (GWAS) have led to rapid growth in detecting genetic variants associated with various phenotypes. Owing to a great number of publicly accessible GWAS summary statistics, and the difficulty in obtaining individual-level genotype data, many existing gene-based association tests have been adapted to require only GWAS summary statistics rather than individual-level data. However, these association tests are restricted to unrelated individuals and thus do not apply to family samples directly. Moreover, due to its flexibility and effectiveness, the linear mixed model has been increasingly utilized in GWAS to handle correlated data, such as family samples. However, it remains unknown how to perform gene-based association tests in family samples using the GWAS summary statistics estimated from the linear mixed model. In this study, we show that, when family size is negligible compared to the total sample size, the diagonal block structure of the kinship matrix makes it possible to approximate the correlation matrix of marginal Z scores by linkage disequilibrium matrix. Based on this result, current methods utilizing summary statistics for unrelated individuals can be directly applied to family data without any modifications. Our simulation results demonstrate that this proposed strategy controls the type 1 error rate well in various situations. Finally, we exemplify the usefulness of the proposed approach with a dental caries GWAS data set.

Effects of lidocaine, dexmedetomidine, and their combination infusion on postoperative nausea and vomiting following laparoscopic hysterectomy: a randomized controlled trial.

BACKGROUND: A few studies have reported that administration of lidocaine and dexmedetomidine relieves the incidence of postoperative nausea and vomiting (PONV). We explored whether combined infusion of lidocaine plus dexmedetomidine had lower occurrence of PONV undergoing laparoscopic hysterectomy with general anesthesia. METHODS: A total of 248 women undergoing elective laparoscopic hysterectomy were allocated into the following four groups: the control group (group C, n = 62) received an equal volume of saline, the lidocaine group (group L, n = 62) received intravenous lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion), the dexmedetomidine group (group D, n = 62) received dexmedetomidine administration (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion), and the lidocaine plus dexmedetomidine group (group LD, n = 62) received combination of lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion) and dexmedetomidine administration (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion). The primary outcome was the incidence of nausea, vomiting, and PONV during the first 48 h after surgery. The secondary outcomes included the incidence of total 24 h PONV after surgery, intraoperative remifentanil requirement, postoperative pain visual analogue scale (VAS) scores and fentanyl consumption, the incidence of bradycardia, agitation, shivering, and mouth dry during post-anesthesia care unit (PACU) stay period. RESULTS: The occurrence of nausea and PONV in group LD (5.0 and 8.3%) at 0-2 h after operation was lower than group C (21.7 and 28.3%) (P < 0.05). There was no statistically significant difference with respect to occurrence of nausea and PONV in groups L (13.3 and 20.0%) and D (8.3 and 13.3%) at 0-2 h after operation compared to group C (21.7 and 28.3%). The incidence of nausea, vomiting, and PONV at 2-24 and 24-48 h after surgery in all four groups was not statistically significant. The incidence of total 24 h PONV in group LD (33.3%) was significantly decreased compared to group C (60.0%) (P < 0.05). The cumulative consumption of fentanyl at 6 and 12 h after surgery was significantly reduced in group LD compared to other three groups (P < 0.05). The pain VAS scores were significantly decreased at 2, 6, and 12 h after operation in group LD compared to other three groups (P < 0.05). Remifentanil dose in the intraoperative period was significantly lower in groups LD and D compared with groups C and L (P < 0.05). The number of mouth dry, bradycardia, and over sedation during the PACU stay period was markedly increased in group LD (28.3, 30.0, and 35.0%, respectively) compared with groups C (1.7, 1.7, and 3.3%, respectively) and L (3.3, 5.0, and 6.7%, respectively) (P < 0.05). CONCLUSIONS: Lidocaine combined with dexmedetomidine infusion markedly decreased the occurrence of nausea and PONV at 0-2 h as well as the total 24 h PONV. However, it significantly increased the incidence of mouth dry, bradycardia, and over sedation during the PACU stay period after laparoscopic hysterectomy with general anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03809923 ), registered on January 18, 2019.

Carcinoma cuniculatum in maxillary gingiva mimicking verruciform xanthoma: a case report.

Carcinoma cuniculatum (CC) is a rare and well-differentiated clinicopathological variant of squamous cell carcinoma (SCC) that is not common in head and neck. It is defined histologically by the infiltrative pattern of a deep, broad, and complex proliferation of stratified squamous epithelium with keratin cores and keratin-filled crypts. It has a propensity for local invasion and rare metastasis. This case report describes a 39-year-old man who was referred to our hospital with painful swelling in the right maxillary gingiva for 1 month and restriction of mouth opening for 1 week. Two biopsy examinations were negative for the diagnosis of malignancy, and the patient was misdiagnosed with verruciform xanthoma before an accurate diagnosis of CC. The biopsy reports were not in line with the imaging findings and clinical manifestations. Finally, he was diagnosed based on the combination of clinical manifestations and the pathological findings. Our case report provided a thorough clinical and histopathologic case of CC in maxillary gingiva, together with a brief review of the literature. In addition, we highlighted the difficulties in arriving at this uncommon diagnosis, and discussed the diagnosis of CC based on the combination of clinical manifestations and the pathological findings. To our knowledge, this is a very rare case of CC of the gingiva mimicking verruciform xanthoma.

Organic matter removal and membrane fouling mitigation during algae-rich surface water treatment by powdered activated carbon adsorption pretreatment: Enhanced by UV and UV/chlorine oxidation.

In this work, UV and UV/chlorine (UV/Cl) were employed to enhance powdered activated carbon (PAC) adsorption pretreatment prior to ultrafiltration process for algae-contaminated surface water treatment. Their performance on membrane fouling mitigation and organic pollutant rejection was systematically evaluated. A comparative experiment was conducted under varying pollution degrees of algal extracellular organic matter (EOM) contamination in surface river water. The results indicated that UV/PAC and UV/Cl/PAC pretreatment effectively enhanced the removal of dissolved organic carbon (DOC) and UV-absorbing at 254 nm (UV254). The characteristics of feed water after pretreatments were investigated through apparent molecular-weight (MW) distribution and fluorescence parallel factor analysis (PARAFAC). In regard to membrane fouling mitigation, UV/Cl/PAC noticeably decreased reversible and irreversible fouling resistance simultaneously and UV/PAC preferred reducing reversible membrane fouling. Combined fouling modeling was operated to scrutinize the fouling mitigation mechanisms and standard pore blocking was proved to be dominant during the filtration process. Moreover, the UV/Cl and UV/Cl/PAC pretreatments were proved positive for emerging micropollutants degradation and disinfection by-products formation potential reduction. The results suggested that UV and UV/Cl are likely strategies to enhance the efficiency of PAC adsorption pretreatments prior to ultrafiltration during algae-contaminated water treatment.