The emergence and successful elimination of SARS-CoV-2 dominant strains with increasing epidemic potential in Taiwan's 2021 outbreak.

Taiwan's experience with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 guided its development of strategies to defend against SARS-CoV-2 in 2020, which enabled the successful control of Coronavirus disease 2019 (COVID-19) cases from 2020 through March 2021. However, in late-April 2021, the imported Alpha variant began to cause COVID-19 outbreaks at an exceptional rate in Taiwan. In this study, we aimed to determine what epidemiological conditions enabled the SARS-CoV-2 Alpha variant strains to become dominant and decline later during a surge in the outbreak. In conjunction with contact-tracing investigations, we used our bioinformatics software, CoVConvert and IniCoV, to analyze whole-genome sequences of 101 Taiwan Alpha strains. Univariate and multivariable regression analyses revealed the epidemiological factors associated with viral dominance. Univariate analysis showed the dominant Alpha strains were preferentially selected in the surge's epicenter (p = 0.0024) through intensive human-to-human contact and maintained their dominance for 1.5 months until the Zero-COVID Policy was implemented. Multivariable regression found that the epidemic periods (p = 0.007) and epicenter (p = 0.001) were two significant factors associated with the dominant virus strains spread in the community. These dominant virus strains emerged at the outbreak's epicenter with frequent human-to-human contact and low vaccination coverage. The Level 3 Restrictions and Zero-COVID policy successfully controlled the outbreak in the community without city lockdowns. Our integrated method can identify the epidemiological conditions for emerging dominant virus with increasing epidemiological potential and support decision makers in rapidly containing outbreaks using public health measures that target fast-spreading virus strains.

Use of everolimus following kidney transplantation during pregnancy: A case report and systematic review.

OBJECTIVE: There is limited safety data on the use of everolimus during pregnancy. In this study, we present the maternal and neonatal outcomes of everolimus used throughout the course of pregnancy and conducted a systematic review of reports of everolimus use after organ transplantation during pregnancy. CASE REPORT: A woman with type 1 diabetes who underwent kidney transplantation was treated with tacrolimus, everolimus, and prednisolone. Two years later, she became pregnant. At 27 weeks of gestation, an emergent cesarean delivery was performed owing to severe preeclampsia and fetal distress. No congenital malformation was noted in the baby at a corrected age of 4 months, and the maternal renal function remained stable. CONCLUSION: Our systematic review did not identify evidence of teratogenicity in babies exposed to everolimus as an immunosuppressant after transplantation. To better assess the risk of exposure to everolimus during pregnancy, all cases of new pregnancies occurring in transplant recipients receiving treatment with mammalian target of rapamycin inhibitor inhibitors should be reported.

Clinical evaluation of 3D-printed zirconia crowns fabricated by selective laser melting (SLM) for posterior teeth restorations: Short-term pilot study.

Background/purpose: Zirconia crowns (ZrC) without veneering porcelain have become an effective alternative in clinical practice. Monolithic zirconia restorations fabricated by the dry milling method do not have acceptable clinical properties. This study evaluated the periodontal qualities of three-dimensional printed ZrC using the modified United States Public Health Service (USPHS) criteria. Materials and methods: A total of 15 patients who required dental crowns were recruited, and all 15 teeth were restored with digital 3D-printed ZrC. All crowns were assessed at the time of crown placement and 2, 6, and 24 weeks post-placement. Clinical parameters, including plaque index, gingival index, probing depth, crown marginal integrity, and attrition of the antagonist's teeth, were evaluated and recorded. Results: According to the Modified California Dental Association quality evaluation system, 100% of the crowns received satisfactory grades. Despite the significant increase in plaque index and gingival index at two weeks post-ZrC placement, there was no deterioration in probing depth. Moreover, there was discard usage of ZrC on the antagonist's teeth at 24 weeks posttreatment. Of the 15 crowns, one tooth had to be extracted due to a vertical root fracture. Overall, the digital 3D-printed crowns showed no adverse effects on periodontal tissues after 24 weeks of follow-up. Conclusion: The 3D-printed ZrC showed no periodontal problems. It can serve as an alternative for patients, particularly those with high esthetic expectations.

Synergistic Effect of Static Magnetic Fields and 3D-Printed Iron-Oxide-Nanoparticle-Containing Calcium Silicate/Poly-ε-Caprolactone Scaffolds for Bone Tissue Engineering.

In scaffold-regulated bone regeneration, most three-dimensional (3D)-printed scaffolds do not provide physical stimulation to stem cells. In this study, a magnetic scaffold was fabricated using fused deposition modeling with calcium silicate (CS), iron oxide nanoparticles (Fe3O4), and poly-ε-caprolactone (PCL) as the matrix for internal magnetic sources. A static magnetic field was used as an external magnetic source. It was observed that 5% Fe3O4 provided a favorable combination of compressive strength (9.6 ± 0.9 MPa) and degradation rate (21.6 ± 1.9% for four weeks). Furthermore, the Fe3O4-containing scaffold increased in vitro bioactivity and Wharton's jelly mesenchymal stem cells' (WJMSCs) adhesion. Moreover, it was shown that the Fe3O4-containing scaffold enhanced WJMSCs' proliferation, alkaline phosphatase activity, and the osteogenic-related proteins of the scaffold. Under the synergistic effect of the static magnetic field, the CS scaffold containing Fe3O4 can not only enhance cell activity but also stimulate the simultaneous secretion of collagen I and osteocalcin. Overall, our results demonstrated that Fe3O4-containing CS/PCL scaffolds could be fabricated three dimensionally and combined with a static magnetic field to affect cell behaviors, potentially increasing the likelihood of clinical applications for bone tissue engineering.

Early diagnosis of Gitelman syndrome in a young child: A case report.

BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterized by renal wasting hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is usually caused by mutations in the gene SLC12A3, which encodes the thiazide-sensitive Na-Cl cotransporter. GS is not usually diagnosed until late childhood or adulthood. CASE SUMMARY: Here, we report the case of a one-year-old girl who was brought to the emergency department due to persistent vomiting for two days. On admission to our hospital, generalized weakness was observed, and laboratory investigations revealed severe hypokalemia (1.9 mmol/L). However, persistent hypokalemia was observed during outpatient follow-up. Suspicion of the GS phenotype was assessed via the patient's clinical presentation, family history, and biochemical analysis of blood and urine. Further genetic analysis was performed for her and her family by exon-wide sequencing analysis of the gene SLC12A3. The genetic diagnosis of GS was established in the Taiwanese family with three affected individuals, two of whom were children (7 years/17 years) without obvious symptoms, with the youngest being only one year old (patient in our case). CONCLUSION: We successfully demonstrated the early diagnosis of GS using family genetic analysis. Any instances of hypokalemia should not be neglected, as early detection of GS with suitable treatment can prevent patients from potentially life-threatening complications.

Impact of intrinsic sphincter deficiency on mid-urethral sling outcomes.

INTRODUCTION AND HYPOTHESIS: Our primary objective was to study outcomes of patients with intrinsic sphincter deficiency (ISD) following mid-urethral slings (MUS) at 1-year. Our secondary objective was to delineate factors affecting success in these patients. METHODS: Six hundred eighty-eight patients who had MUS between January 2004 and April 2017 were reviewed retrospectively; 48 women were preoperatively diagnosed with ISD. All completed urodynamic studies and validated quality-of-life (QOL) questionnaires at baseline and 1 year. Primary outcomes were objective and subjective cure of stress incontinence, defined as no involuntary urine leakage during filling cystometry and 1-h pad test < 2 g and negative response to Urogenital Distress Inventory-6 Question 3. Ultrasound was performed to determine tape position, urethral mobility and kinking at 1 year. RESULTS: Women with ISD had significantly lower objective and subjective cure rates of 52.1% and 47.9%, respectively, compared to an overall of 88.2% and 85.9%. QOL scores significantly improved in those with successful surgeries. The sling type did not make a difference. Multivariate logistic regression identified reduced urethral mobility [OR 2.11 (1.24-3.75)], lower maximum urethral closure pressure (MUCP) [OR 1.61 (1.05-3.41)] and tape position [OR 3.12 (1.41-8.71)] to be associated with higher odds of failed slings for women with ISD. CONCLUSIONS: Although there are good overall success in women undergoing MUS, those with ISD have significantly lower cure rates at 1 year. Factors related to failure include reduced urethral mobility, low MUCP and relative tape position further away from the bladder neck. Optimal management of patients with ISD and reduced urethral mobility remains challenging.

Microencapsulated rhEGF to facilitate epithelial healing and prevent scar formation of cesarean wound: A randomized controlled trial.

OBJECTIVE: Cesarean section (CS) is a major surgical intervention that affects women at childbearing age. Scarring from CS potentially causes discomfort and psychological distress. Emerging evidence indicates that epidermal growth factor (EGF) plays crucial roles in wound healing with the potential of minimizing scar formation. This study aims to investigate the effect of microencapsulated recombinant human EGF (Me-EGF) in scar prevention. Silicone gel was incorporated as part of the routine scar treatment. MATERIALS AND METHODS: Healthy women scheduled for cesarean delivery were enrolled and randomized to three groups: (1) no scar treatment, (2) silicone gel only, or (3) silicone gel plus Me-EGF. Vancouver Scar Scale (VSS: vascularity, pigmentation, elasticity, and height) was used for scar assessment at the 6th month and 9th month after CS. RESULTS: A total of 60 women were enrolled, but one patient withdrew due to noncompliance with the follow-up visit requirement. Me-EGF-containing treatment group consistently scored the lowest on every parameter in the VSS scale, followed by silicone gel group, and the group with no scar treatment. Kruskal-Wallis tests indicated significant differences (p < 0.05) between Me-EGF-containing treatment group and the other two groups in vascularity, pigmentation, elasticity, and the VSS total score, at either 6th month, 9th month, or both time points. The only parameter not showing any significant between-group difference was scar height, but the pattern still remained the same, in which Me-EGF group scored better in both month 6 and 9. CONCLUSION: Surgical incisions in lower abdomen posed challenge in scar management. Our findings suggest that Me-EGF is a potential therapeutic option for better wound healing and scar prevention.

Correction: Wei, Y.; et al. Quantify the Protein-Protein Interaction Effects on Adsorption Related Lubricating Behaviors of α-Amylase on a Glass Surface. Polymers 2020, 12, 1658.

The authors wish to make the following corrections to this paper [...].

Quantify the Protein-Protein Interaction Effects on Adsorption Related Lubricating Behaviors of α-Amylase on a Glass Surface.

Dental ceramic material is one of the widely preferred restorative materials to mimic the natural tooth enamel surface. However, it has continuously been degraded because of low wear resistance during mastication in the oral cavity. The friction involved was reduced by introducing the lubricant saliva protein layers to improve the wear resistance of the dental materials. However, little is understood regarding how the protein-protein interactions (PPI) influence the adsorbed-state structures and lubricating behaviors of saliva proteins on the ceramic material surface. The objective of this study is to quantify the influences of PPI effects on the structural changes and corresponding oral lubrications of adsorbed α-amylase, one of the abundant proteins in the saliva, on the dental ceramic material with glass as a model surface. α-Amylase was first adsorbed to glass surface under varying protein solution concentrations to saturate the surface to vary the PPI effects over a wide range. The areal density of the adsorbed protein was measured as an indicator of the level of PPI effects within the layer, and these values were then correlated with the measurements of the adsorbed protein's secondary structure and corresponding friction coefficient. The decreased friction coefficient value was an indicator of the lubricated surfaces with higher wear resistance. Our results indicate that PPI effects help stabilize the structure of α-amylase adsorbed on glass, and the correlation observed between the friction coefficient and the conformational state of adsorbed α-amylase was apparent. This study thus provides new molecular-level insights into how PPI influences the structure and lubricating behaviors of adsorbed protein, which is critical for the innovations of dental ceramic material designs with improved wear resistance.

EPS8 regulates an NLRP3 inflammasome-independent caspase-1 activation pathway in monosodium urate crystal-treated RAW264.7 macrophages.

Gout is an inflammatory arthritis caused by the phagocytosis of monosodium urate (MSU) crystal deposition in joints. NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome-dependent caspase-1 activation is implicated in the processing of interleukin-1ß (IL-1ß), which is the major effector cytokine in the acute inflammatory response of gout. Mechanisms underlying caspase-1 activation remain unclear. Epidermal growth factor receptor pathway substrate no. 8 (Eps8) is a signal transducer and actin filament organizer that plays a key role in lipopolysaccharide-stimulated phagocytosis in macrophages. Here, RAW264.7 macrophages that have no intact NLRP3 inflammasomes were used to investigate the role of Eps8 in MSU crystal-mediated caspase-1 activation. A kinetic study revealed that the induction of Eps8 expression by MSU crystals occurred before NLRP3, p46/p33 caspase-1, and mature IL-1ß in RAW 264.7 cells. In addition, actin cytoskeleton dynamics was required for Eps8 induction and caspase-1 activation in MSU crystal stimulation. Silencing Eps8 had no effect on the basal expression of p46/p33 caspase-1 and NLRP3, but nearly abolished MSU crystal-induced NLRP3 expression and caspase-1 activation. Furthermore, MSU crystals induced Eps8-pro-caspase-1 complex formation and Eps8 formed a stable complex with p33 caspase-1, but not with NLRP3. In summary, our results demonstrated for the first time the importance of Eps8 in MSU crystal-mediated caspase-1 activation without the involvement of NLRP3 inflammasomes.

Urodynamics mixed type urinary incontinence with advanced pelvic organ prolapse, management and outcomes.

Patients with pelvic organ prolapse (POP) often have accompanying lower urinary tract symptoms. Symptoms such as stress urinary incontinence(SUI-UD) and detrusor overactivty(DO) would co-exist in a number of patients. Management entails relieving the obstructive element. To determine the clinical outcome of patients with urodynamics mixed type urinary incontinence(MUI-U) after vaginal pelvic reconstructive surgery(PRS), a retrospective study was conducted. MUI-U was defined as having urodynamic findings of both of DO/DOI (derusor overactivity incontinence) and SUI-UD. Main outcome measures: Objective cure- absence of involuntary detrusor contraction on filling cystometry and no demonstrable leakage of urine during increased abdominal pressure; Subjective cure- assessment index score of <1 on UDI-6 question #2 and #3. Of the 82 patients evaluated, 14 underwent vaginal PRS with concomitant mid-urethral sling(MUS) insertion while 68 had vaginal PRS alone. Pre-operatively, 49(60%) patients had stage III and 33(40%) had stage IV prolapse. Post-operatively, 1-year data shows an objective cure of 56% (46/82) and subjective cure of 54% (44/82). MUI-U was significantly improved. Improvement of SUIUD and results of the 1-hour pad test were more pronounced in patients with concomitant MUS insertion. Ergo, vaginal PRS cures symptoms of MUI-U in >50% of patients and concomitant MUS can be offered to SUI predominant MUI.

Increased Soluble Epoxide Hydrolase in Human Gestational Tissues from Pregnancies Complicated by Acute Chorioamnionitis.

Chorioamnionitis (CAM) is primarily a polymicrobial bacterial infection involving chorionic and amniotic membranes that is associated with increased risk of preterm delivery. Epoxyeicosatrienoic acids (EETs) are eicosanoids generated from arachidonic acid by cytochrome P450 enzymes and further metabolized mainly by soluble epoxide hydrolase (sEH) to produce dihydroxyeicosatrienoic acids (DHETs). As a consequence of this metabolism of EETs, sEH reportedly exacerbates several disease states; however, its role in CAM remains unclear. The objectives of this study were to (1) determine the localization of sEH and compare the changes it undergoes in the gestational tissues (placentas and fetal membranes) of women with normal-term pregnancies and those with pregnancies complicated by acute CAM; (2) study the effects of lipopolysaccharide (LPS) on the expression of sEH in the human gestational tissues; and (3) investigate the effect of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a specific sEH inhibitor, on LPS-induced changes in 14,15-DHET and cytokines such as interleukin- (IL-) 1ß and IL-6 in human gestational tissues in vitro and in pregnant mice. We found that women with pregnancies complicated by acute CAM had higher levels of sEH mRNA and protein in fetal membranes and villous tissues compared to those in women with normal-term pregnancies without CAM. Furthermore, fetal membrane and villous explants treated with LPS had higher tissue levels of sEH mRNA and protein and 14,15-DHET than those present in the vehicle controls, while the administration of AUDA in the media attenuated the LPS-induced production of 14,15-DHET in tissue homogenates and IL-1ß and IL-6 in the media of explant cultures. Administration of AUDA also reduced the LPS-induced changes of 14,15-DHET, IL-1ß, and IL-6 in the placentas of pregnant mice. Together, these results suggest that sEH participates in the inflammatory changes in human gestational tissues in pregnancies complicated by acute CAM.

UNC13C Suppress Tumor Progression via Inhibiting EMT Pathway and Improves Survival in Oral Squamous Cell Carcinoma.

Potential function of UNC13C in variety of cancers including, oral squamous cell carcinoma (OSCC) remains obscure. In the present study, immunohistochemical staining in tissue microarrays containing 268 OSCC samples showed that UNC13C protein levels were inversely correlated with AJCC Stage III and IV (P = 0.002) and death (P = 0.0134). Patients with lower UNC13C expression had a significantly shorter survival (P = 0.0231) than those with higher UNC13C expression. We also identified decreased overall UNC13C expression in oral cancer cell lines. In addition, our functional analysis of UNC13C shows that overexpression of UNC13C inhibited migration and invasion capacities of SCC-9 and SAS cells compared with the empty plasmid transfected cells. Further experiments suggested that transcription factors (Slug, Snail, Twist, and ZEB1) and mesenchymal marker (Vimentin) were down regulated and Tight Junction Protein (Claudin1) was up regulated after UNC13C overexpression in SCC9 and SAS cells. The novel role of UNC13C is revealed for the first time in OSCC. In summary, these results suggest that UNC13C as a novel tumor suppressor and an essential regulator of EMT signaling pathway during OSCC progression, and thus it could be used as a target for preventing oral cancer metastasis.

Clinical relevance and treatment outcomes of vesicovaginal fistula (VVF) after obstetric and gynecologic surgery.

OBJECTIVE: Vesicovaginal fistulas (VVF) are consequences from obstetric and gynecologic surgery. Treatment approach from either abdominal or vaginal route have its own pros and cons. The study aims to present the anatomical, clinical and lower urinary tract symptom outcomes of women with VVF. MATERIALS AND METHODS: A retrospective case series conducted patients with VVF. Data regarding pre-operative evaluation, surgical treatment, and post-operative follow-ups were collected. Surgical approach depended on the cause, type, number, size, location, and time of onset of the fistula. Post-operatively, foley catheter was maintained for at least 1 week with cystoscopy performed prior to removal. Follow-up evaluation included cystoscopy, bladder diary, UDI-6 and IIQ-7 questionnaires and multi-channel urodynamic study. RESULTS: Of the 15 patients that were evaluated, 1 had spontaneous closure, 8 were repaired vaginally and 6 abdominally. Patients repaired vaginally were significantly noted to have a mean age of 50.3 ± 7.1 years with VVFs located adjacent the supra-trigone area having a mean distance of 1.7 ± 0.5 cm from the ureteric orifice. Its operative time and hospital stay were significantly shorter. In contrast, abdominally repaired patients had mean age of 38.0 ± 8.2 years and VVFs with mean distance of 0.4 ± 0.4 cm from the ureteric orifice. Post-operatively, 2 cases (14.2%, 2/14) of VVF recurrence and de novo urodynamic stress incontinence (USI) (25%, 2/8) were noted after vaginal repair and 3 cases (50%, 3/6) of concurrent ureteric injury and overactive bladder after abdominal repair. CONCLUSION: Treatment outcomes for vaginal and abdominal repair yielded good results. Though the vaginal route had higher incidence of recurrence and de novo USI, its less invasiveness, faster recovery period, and no association with post-op overactive bladder made it more preferable than the abdominal approach.

Anterior-apical single-incision mesh surgery (uphold): 1-year outcomes on lower urinary tract symptoms, anatomy and ultrasonography.

INTRODUCTION AND HYPOTHESIS: Our primary objective is to determine the presence of SUI at 6-12 months after surgery. The secondary objective is to determine the objective and subjective outcomes of POP. METHODS: A retrospective study conducted between February 2015 and July 2016 at Chang Gung Memorial Hospital. The subjects had had symptomatic anterior or apical prolapse with stage III or IV and undergone pelvic reconstructive surgery using Uphold™ LITE. Patients completed a 3-day voiding diary, urodynamic study, real-time ultrasonography and validated quality-of-life questionnaires at baseline and 12-month follow-up. Primary outcome was the absence of USI. Secondary outcomes included the objective cure rate of POP, ≤ stage 1 at the anterior/apical vaginal wall, and the subjective cure rate, negative feedback to POPDI-6. RESULTS: Ninety-five women were eligible. Six were excluded because of incomplete data. The postoperative de novo USI and SUI were 22.7 and 19.7%, respectively. There was significant improvement of USI in patients who had MUS insertion (93.8%) and bladder outlet obstruction (96.7%). The objective and subjective cure rate for prolapse was 95.5 and 94.3%, respectively. POP-Q measurements pre- and postoperatively were significantly improved at all points except for Gh and Pb. There was a significant difference in the distance between the bladder neck to the distal end of the mesh during straining both at both the postoperative 3rd month and 1 year. CONCLUSIONS: Uphold™ mesh has a 20% incidence of de novo USI with acceptable objective and subjective cure rates at 1 year postoperatively. The de novo USI rate was high but not bothersome enough to require surgery.

Prophylactic midurethral sling insertion during transvaginal pelvic reconstructive surgery for advanced prolapse patients with high-risk predictors of postoperative de novo stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate the clinical outcome of continent women with high-risk predictors for de novo stress urinary incontinence (SUI) offered prophylactic midurethral sling (MUS) insertion during vaginal pelvic reconstructive surgery (PRS) for advanced pelvic organ prolapse (POP). MATERIALS AND METHODS: This was a prospective cohort study in patients with POP stage ≥ 3 and maximum urethral closure pressure (MUCP) <60 cmH2O and functional urethral length (FUL) <2 cm. Patients were divided into PRS and PRS + MUS groups. Surgery commenced with vaginal hysterectomy, application of Uphold® and insertion of MUS to the PRS + MUS group. Main outcome measures were incidence of de novo urodynamic stress incontinence (USI), lower urinary tract symptoms (LUTS), quality of life (QoL), and topographic and anatomical relationship of implanted mesh. RESULTS: Based on sample size calculation, 40 patients were recruited-20 in each group. Rate of de novo USI in PRS + MUS was 5% objectively and 10% subjectively, while in the PRS it was 50% objectively and 60% subjectively. No significant difference was noted in patient demographics. Intraoperative blood loss was greater for PRS + MUS but was not statistically significant. No organ injuries, mesh exposure, or infections occurred. Postoperatively, MUCP significantly increased from 43.3 ± 8.9 to 58.5 ± 19.2 cmH2O and FUL from 17.2 ± 1.9 to 20.3 ± 3.1 mm in the PRS + MUS group. Residual urine significantly decreased. No patient had bladder outlet obstruction (BOO). Sonographic assessment showed no difference in mesh mobility with urethral kinking observed in 11 (55%) patients with MUS. CONCLUSION: Based on a validated small sample, prophylactic MUS for continent women at high risk for postoperative USI with advanced POP lowers its incidence to 5%. Continence is achieved in 95%. Concern for complications, LUTS, and QoL did not significantly differ.