Perioperative outcomes of bilateral axillo-breast approach robotic thyroidectomy (BABART) versus minimally invasive thyroidectomy (MIT): a systematic review and meta-analysis.

Minimally invasive thyroidectomy (MIT) is increasingly being used for the thyroid tumors. The comparison of bilateral axillo-breast approach robotic thyroidectomy (BABART) with other MIT has not yet led to a unified conclusion with regard to surgical outcomes. To conduct a systematic review and meta-analysis of the literature on the surgical outcomes of BABART compared with MIT. We performed a systematic search in PubMed, Web of Science, Embase and Cochrane Library database for randomized control trials (RCTs) and non-RCTs that compare BABART to MIT. The primary outcomes included perioperative, postoperative complications. The odds ratio (OR) and mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CIs). Nine studies, comprising 3645 patients, were included in the meta-analysis. Our findings indicated that there were no significant differences in hospital stay, number of retrieved lymph nodes, recurrent laryngeal nerve (RLN) injury, and vocal cord dysfunction between BABRT and MIT. However, BABART was associated with a shorter operation time (MD = - 21.45 min, 95% CI [- 47.27, 4.38], p = 0.1) and lower rate of permanent hypoparathyroidism (OR = 0.42, 95% CI [0.20, 0.88], p = 0.02). Additionally, the MIT group had reduced postoperative pain score (MD = 0.45, 95% CI [0.02, 0.88], p = 0.04) and lower rate of hypocalcemia (OR = 2.31, 95% CI [1.04, 5.13], p = 0.04) than the BABART group. In comparison with MIT, BABART exhibits better results in terms of operative time and the rate of permanent hypoparathyroidism, with no significant difference in hospital stay, number of retrieved lymph nodes, RLN injury, and vocal cord dysfunction. However, the postoperative pain score and the rate of hypocalcemia of MIT are slightly better that of BABART.

ER+/PR- phenotype exhibits more aggressive biological features and worse outcome compared with ER+/PR+ phenotype in HER2-negative inflammatory breast cancer.

The loss of progesterone receptor (PR) often predicts worse biological behavior and prognosis in estrogen receptor-positive (ER +) breast cancer. However, the impact of PR status on inflammatory breast cancer (IBC) has not been studied. Therefore, the purpose of our study was to investigate the influence of PR on IBC. Patients with ER+ and HER2-negative IBC were selected from the Surveillance, Epidemiology and End Results database. Pearson's χ2 test was used to compare the clinicopathological characteristics between patients with estrogen receptor-positive/progesterone receptor-positive (ER+/PR +) and patients with estrogen receptor-positive/progesterone receptor-negative (ER+/PR-). Univariate and multivariate analyses were performed to investigate the effects of PR status on the breast cancer-specific survival (BCSS) and overall survival (OS) in IBC. Overall, 1553 patients including 1157 (74.5%) patients with ER+/PR+ and 396 (25.5%) patients with ER+/PR- were analyzed in our study. The patients with ER+/PR- were more likely to be high histological grade (p < 0.001) and liver metastasis (p = 0.045) compared to patients with ER+/PR+. Despite higher chance of receiving chemotherapy (83.6% vs 77.3%, P = 0.008), patients with ER+/PR- showed worse BCSS (5-year BCSS rate, 34.3% vs 51.3%, P < 0.001) and OS (5-year OS rate, 31.3% vs 46.1%, P < 0.001) compared with ER+/PR+ phenotype. Multivariate survival analysis showed that patients with ER+/PR- still had worse BCSS (hazard ratios [HR]: 1.764, 95% confidence intervals [CI] 1.476-2.109, P < 0.001) and OS (HR: 1.675, 95% CI 1.411-1.975, P < 0.001) than ER+/PR+ phenotype. Furthermore, patients with ER+/PR- showed worse outcomes than ER+/PR+ phenotype in most subgroups, especially in patients with younger age (≤ 60 years), lower histological grade, lymph node involved and distant metastasis. Patients with ER+/PR- had more aggressive biological behaviors and worse outcomes than patients with ER+/PR+ in IBC. Stronger treatments maybe needed for IBC patients with ER+/PR-.

Mechanical transmission of dengue virus by Aedes aegypti may influence disease transmission dynamics during outbreaks.

BACKGROUND: Dengue virus outbreaks are increasing in number and severity worldwide. Viral transmission is assumed to require a minimum time period of viral replication within the mosquito midgut. It is unknown if alternative transmission periods not requiring replication are possible. METHODS: We used a mouse model of dengue virus transmission to investigate the potential of mechanical transmission of dengue virus. We investigated minimal viral titres necessary for development of symptoms in bitten mice and used resulting parameters to inform a new model of dengue virus transmission within a susceptible population. FINDINGS: Naïve mice bitten by mosquitoes immediately after they took partial blood meals from dengue infected mice showed symptoms of dengue virus, followed by mortality. Incorporation of mechanical transmission into mathematical models of dengue virus transmission suggest that this supplemental transmission route could result in larger outbreaks which peak sooner. INTERPRETATION: The potential of dengue transmission routes independent of midgut viral replication has implications for vector control strategies that target mosquito lifespan and suggest the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes. FUNDING: This study was funded by grants from the National Health Research Institutes, Taiwan (04D2-MMMOST02), the Human Frontier Science Program (RGP0033/2021), the National Institutes of Health (1R01AI143698-01A1, R01AI151004 and DP2AI152071) and the Ministry of Science and Technology, Taiwan (MOST104-2321-B-400-016).

Use of unmanned ground vehicle systems in urbanized zones: A study of vector Mosquito surveillance in Kaohsiung.

Dengue fever is a vector-borne disease that has become a serious global public health problem over the past decade. An essential aspect of controlling and preventing mosquito-borne diseases is reduction of mosquito density. Through the process of urbanization, sewers (ditches) have become easy breeding sources of vector mosquitoes. In this study, we, for the first time, used unmanned ground vehicle systems (UGVs) to enter ditches in urban areas to observe vector mosquito ecology. We found traces of vector mosquitoes in ~20.7% of inspected ditches, suggesting that these constitute viable breeding sources of vector mosquitoes in urban areas. We also analyzed the average gravitrap catch of five administrative districts in Kaohsiung city from May to August 2018. The gravitrap indices of Nanzi and Fengshan districts were above the expected average (3.26), indicating that the vector mosquitoes density in these areas is high. Using the UGVs to detect positive ditches within the five districts followed by insecticide application generally yielded good control results. Further improving the high-resolution digital camera and spraying system of the UGVs may be able to effectively and instantly monitor vector mosquitoes and implement spraying controls. This approach may be suitable to solve the complex and difficult task of detecting mosquito breeding sources in urban ditches.

Comparison of Fan-Traps and Gravitraps for Aedes Mosquito Surveillance in Taiwan.

A key component of integrated vector management strategies is the efficient implementation of mosquito traps for surveillance and control. Numerous trap types have been created with distinct designs and capture mechanisms, but identification of the most effective trap type is critical for effective implementation. For dengue vector surveillance, previous studies have demonstrated that active traps utilizing CO2 attractant are more effective than passive traps for capturing Aedes mosquitoes. However, maintaining CO2 supply in traps is so labor intensive as to be likely unfeasible in crowded residential areas, and it is unclear how much more effective active traps lacking attractants are than purely passive traps. In this study, we analyzed Aedes capture data collected in 2019 from six urban areas in Kaohsiung City to compare Aedes mosquito catch rates between (passive) gravitraps and (active) fan-traps. The average gravitrap index (GI) and fan-trap index (FI) values were 0.68 and 3.39 respectively at peak catch times from June to August 2019, with consistently higher FI values calculated in all areas studied. We compared trap indices to reported cases of dengue fever and correlated them with weekly fluctuations in temperature and rainfall. We found that FI trends aligned more closely with case numbers and rainfall than GI values, supporting the use of fan-traps for Aedes mosquito surveillance and control as part of broader vector management strategies. Furthermore, combining fan-trap catch data with rapid testing for dengue infections may improve the early identification and prevention of future disease outbreaks.

Use of seroprevalence to guide dengue vaccination plans for older adults in a dengue non-endemic country.

A shift in dengue cases toward the adult population, accompanied by an increased risk of severe cases of dengue in the elderly, has created an important emerging issue in the past decade. To understand the level of past DENV infection among older adults after a large dengue outbreak occurred in southern Taiwan in 2015, we screened 1498 and 2603 serum samples from healthy residents aged ≥ 40 years in Kaohsiung City and Tainan City, respectively, to assess the seroprevalence of anti-DENV IgG in 2016. Seropositive samples were verified to exclude cross-reaction from Japanese encephalitis virus (JEV), using DENV/JEV-NS1 indirect IgG ELISA. We further identified viral serotypes and secondary DENV infections among positive samples in the two cities. The overall age-standardized seroprevalence of DENV-IgG among participants was 25.77% in Kaohsiung and 11.40% in Tainan, and the seroprevalence was significantly higher in older age groups of both cities. Although the percentages of secondary DENV infection in Kaohsiung and Tainan were very similar (43.09% and 44.76%, respectively), DENV-1 and DENV-2 spanned a wider age range in Kaohsiung, whereas DENV-2 was dominant in Tainan. As very few studies have obtained the serostatus of DENV infection in older adults and the elderly, this study highlights the need for further investigation into antibody status, as well as the safety and efficacy of dengue vaccination in these older populations.

Releasing Intracellular NS1 from Mosquito Cells for the Detection of Dengue Virus-Infected Mosquitoes.

Dengue virus (DENV), the pathogen that causes dengue fever, is mainly transmitted by Aedes aegypti. Surveillance of infected mosquitoes is a major component of integrated mosquito control methods for reducing the risk of vector-born disease outbreaks. However, a specialized rapid test for DENV detection in mosquitoes is not currently available. Utilizing immunoblotting, we found that the secretion of NS1 from both a DENV-infected mosquito cell line and mosquito bodies was below the detection threshold. However, when Triton X-100 was used to lyse infected mosquitoes, intracellular NS1 was released, and could then be effectively detected by the NS1 rapid test. The distribution of DENV NS1 in intrathoracically infected mosquitoes was different from that of orally infected mosquitoes. Next, we performed sensitivity tests by bisecting mosquitoes longitudinally; one half of each mosquito was subjected to the NS1 rapid test while the other half was used for qPCR confirmation. This modified test had a sensitivity of nearly 90% from five days post-infection onwards, while DENV had escaped from the midgut barrier. This adapted test offers a valuable, easy-to-use tool for mosquito surveillance, which is a crucial component of DENV disease control.

Epidemiological analysis of the Kaohsiung city strategy for dengue fever quarantine and epidemic prevention.

BACKGROUND: Dengue is endemic in over 100 countries and is an important public health problem worldwide. Dengue fever is not endemic in Taiwan; the importation of dengue viruses from neighboring countries via close commercial links and air travel is considered to be the cause of local outbreaks. Therefore, efforts toward disease control have focused on preventing the importation of dengue into Taiwan. In this study, we investigated the relationships between the numbers of imported and indigenous dengue cases to test the validity of this strategy. METHODS: Data on cases of dengue fever that occurred between 2013 and 2018 were obtained from the surveillance systems of the Taiwan Center for Disease Control and Kaohsiung City Health Department. Standard epidemiological data, including the monthly numbers of indigenous and imported cases of dengue, were calculated. Potential associations between the numbers of indigenous and imported cases were investigated using correlation analyses. RESULTS: We identified a possible relationship between the period of disease concealment and the number of imported dengue cases, which resulted in epidemics of indigenous dengue fever within local communities. Further analysis of confirmed cases during previous epidemics in Kaohsiung City found that the risk of indigenous dengue fever may be related to the likelihood that patients with imported dengue fever will stay within local communities. CONCLUSION: Given the correlations found between imported and indigenous cases of dengue fever, as well as the relationship between the disease concealment period and the risk of indigenous dengue fever, prevention of disease importation and efficient identification of dengue cases within high-risk communities remain the major priorities for disease control.

Elevation of cell wall chitin via Ca2+ -calcineurin-mediated PKC signaling pathway maintains the viability of Candida albicans in the absence of ß-1,6-glucan synthesis.

ß-1,6-glucan is an important cell wall component of Candida albicans. Deleted mutants of the two ß-1,6-glucan synthase genes KRE6 and SKN1 are viable albeit with a range of defects including slow growth. It remains unclear whether ß-1,6-glucan synthesis is not required under culture conditions or compensatory mechanisms exist in C. albicans. Here, we report that depleting ß-1,6-glucan synthases leads to a significant increase in cell wall chitin levels through the posttranscriptional regulation of the chitin synthase Chs3 which maintains cell viability. And depleting ß-1,6-glucan synthases in chs3Δ/Δ cells results in cell death. The elevation of cell wall chitin is mediated by the activation of the PKC signaling pathway and an unknown pathway(s) involving Ca2+ -calcineurin. Also, kre6Δ/Δ skn1Δ/Δ cells are not more susceptible to caspofungin, the antifungal drug that inhibits ß-1,3-glucan synthases, suggesting that ß-1,3-glucan has no role in compensating ß-1,6-glucan synthesis. Given the vital importance of elevating chitin synthesis in the absence of ß-1,6-glucan synthesis in C. albicans, antifungal drugs targeting ß-1,6-glucan and chitin synthesis could be used in combination therapies.

The PP2A regulatory subunits, Cdc55 and Rts1, play distinct roles in Candida albicans' growth, morphogenesis, and virulence.

Protein phosphatase-2A (PP2A) is a heterotrimeric enzyme composed of a catalytic subunit, a regulatory subunit, and a structural subunit. In Candida albicans, Cdc55 and Rts1 have been identified as possible regulatory subunits of PP2A containing the catalytic subunit Pph21 and structural subunit Tpd3. The Tpd3-Pph21 phosphatase regulates cell morphogenesis and division. However, the functions of Cdc55 and Rts1 remain unclear. Here, we constructed cdc55Δ/Δ and rts1Δ/Δ mutants and found that they exhibit different defects in multiple phenotypes although both show similar hyperphosphorylation of the septin Sep7 and aberrant septin organization. Under yeast growth conditions, the cdc55Δ/Δ mutant grows slowly as pseudohyphae with some cells lacking the nucleus, while rts1Δ/Δ cells are round and enlarged and seem to undergo incomplete cell separation producing multinucleated cells. Strong chitin deposition occurs at the septum of cdc55Δ/Δ cells and on the surface of rts1Δ/Δ cells, which likely contributes to increased susceptibility to caspofungin. Also, cdc55Δ/Δ exhibits severe defects in hyphal and biofilm formation, while rts1Δ/Δ is partially defective. Both mutants show reduced virulence in mice, suggesting that PP2A-B subunits could serve as potential antifungal targets.

Phosphatidate phosphatase Pah1 has a role in the hyphal growth and virulence of Candida albicans.

Phosphatidate phosphatases play essential roles in lipid metabolism by converting phosphatidic acid to diacylglycerol. Here, we have investigated the roles of a phosphatidate phosphatase, Pah1, in the fungal pathogen Candida albicans. Deleting PAH1 causes multiple phenotypes, especially severe hyphal defects, increased sensitivity to cell wall stress, and reduced virulence in mice. By qPCR, we detected a significant downregulation of hyphal-specific genes including two key hyphal-promoting genes UME6 and HGC1. Overexpression of UME6 in pah1Δ/Δ cells largely restored the hyphal growth, indicating that the reduced expression of UME6 is primarily responsible for the hyphal defects. We also detected decreased expression of three hyphal-promoting transcription factors EFG1, FLO8, and CPH1 in pah1 mutants, consistent with the reduced expression of UME6. Furthermore, the pah1Δ/Δ mutant exhibited increased sensitivity to cell wall stress. During systemic infection of mice, the mutant showed significantly impaired ability to colonize the kidney and to kill the host. Together, C. albicans PAH1 plays an important role in hyphal growth, adaptability to environmental stresses, and virulence. Thus, Pah1 could be targeted for the development of new antifungal drugs.

PP2A-Like Protein Phosphatase (Sit4) Regulatory Subunits, Sap155 and Sap190, Regulate Candida albicans' Cell Growth, Morphogenesis, and Virulence.

PP2A-like phosphatases share high homology with PP2A enzymes and are composed of a catalytic subunit and a regulatory subunit. In Candida albicans, the PP2A-like catalytic subunit SIT4 regulates cell growth, morphogenesis, and virulence. However, the functions of its regulatory subunits remain unclear. Here, by homology analysis and co-IP experiments, we identified two regulatory subunits of SIT4 in C. albicans, SAP155 (orf19.642) and SAP190 (orf19.5160). We constructed sit4Δ/Δ, sap155Δ/Δ, sap190Δ/Δ, and sap155Δ/Δ sap190Δ/Δ mutants and found that deleting SAP155 had no apparent phenotypic consequence, while deleting SAP190 caused slow growth, hypersensitivity to cell wall stress, abnormal morphogenesis in response to serum or genotoxic stress (HU and MMS), less damage to macrophages, and attenuated virulence in mice. However, deleting both SAP155 and SAP190 caused significantly stronger defects, which was similar to deleting SIT4. Together, our results suggest that SAP190 is required for the function of SIT4 and that SAP155 can partially compensate for the loss of SAP190 in C. albicans. Given the vital role of these regulatory subunits of SIT4 in C. albicans physiology and virulence, they could serve as potential antifungal targets.

Dengue fever scoring system: new strategy for the early detection of acute dengue virus infection in Taiwan.

BACKGROUND/PURPOSE: Dengue fever is an important public health problem in Southern Taiwan. The purpose of this study was to develop a dengue scoring system using a three-stage process, which may be used as a guidance tool for the early diagnosis of dengue fever. METHODS: A retrospective study was conducted to identify factors useful for the early diagnosis of dengue fever. We assessed the clinical and laboratory features of 89 adult patients with dengue from 2002 to 2004 at a community-based hospital. They were compared with 14 patients with scrub typhus, 104 with Q fever, and 35 with murine typhus, which might present similar symptoms and signs as dengue infection. A scoring system was designed after analysis of the retrospective study and with the assistance of 10 expert clinicians. For the second stage, we evaluated efficiency in differentiating dengue fever from Q fever, scrub typhus and murine typhus in three hospitals from 2002 to 2005. For the third stage, we prospectively used the dengue scoring system for 498 cases that clinically were suspected as having dengue infection in the city of Kaohsiung from January 2006 to September 2006. RESULTS: The performance of the scoring system was 88.1% sensitivity, 94.9% specificity, 95.7% positive predictive value (PPV), and 86.1% negative predictive value (NPV). Evaluation of the scoring system at the third stage revealed 90.7% sensitivity, 86.9% specificity, 81.4% PPV, and 93.6% NPV. CONCLUSION: The dengue scoring system had a high NPV that might be helpful in the early diagnosis of dengue fever in adults before laboratory data are available.