From balance to imbalance: disruption of plasma glutathione concentration in micropapillary thyroid carcinoma.

BACKGROUND: Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects. MATERIALS AND METHODS: Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups. RESULTS: The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group (p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects (p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients (p < 0.01). CONCLUSION: These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC.

A computational approach to assessing the prognostic implications of BRAF and RAS mutations in patients with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, posing a growing clinical challenge. PTC exhibits two age-related peaks, with established risk factors including family history and radiation exposure. Managing even low-risk, localized PTC cases remain complex, with growing interest in active surveillance as an alternative to immediate surgery. This study employed single-cell RNA sequencing (scRNA-Seq) to explore the predictive value of BRAF and RAS mutations in PTC, shedding light on their impact on disease progression and outcomes. The analyses emphasized the significance of BRAF and RAS mutations in tumor advancement, particularly the unique BRAF V600E mutation associated with aggressive features. The methodology involved scRNA-Seq analysis of PTC and normal samples, unveiling distinct cell clusters and indicating upregulated BRAF and RAS genes. Pathway enrichment analysis highlighted altered biological processes and immune-related pathways in PTC. The study consolidated previous research showing the prevalence of BRAF and RAS mutations in PTC, subtypes with distinct molecular profiles, and the impact of TERT promoter mutations on disease severity. In summary, this study unveils the complex interplay of genetic mutations and the cellular microenvironment in PTC through scRNA-Seq. The upregulated BRAF and RAS genes suggest their roles as PTC drivers, and pathway enrichment reveals alterations in immune-related processes. This synthesis of prior research enhances our understanding of PTC's molecular foundations, informing better prognosis and personalized treatment approaches. These insights advance the landscape of PTC management and provide directions for further research.

The role of rs2236242 at SERPINA12 gene and vaspin level on papillary thyroid carcinoma.

Several studies showed that adipokines are associated with types of cancer which are documented to be effective in cancer biology. This study aimed to determine the relationship between vaspin rs2236242 polymorphism and the vaspin level with papillary thyroid carcinoma (PTC), and multinodular goiter (MNG). In this cross-sectional study, we recruited 170 candidates. Ninety patients with newly diagnosed (PTC 60 patients and MNG 30 patients), and 80 participants as a control group referred to Shariati Hospital, Tehran, Iran, were enrolled in the study. The vaspin hormone measurements were conducted utilizing the Elisa Kit. Using Tetra amplification resistant-mutation system polymerase chain reaction (T-ARMS-PCR), the genotype of single nucleotide polymorphism (SNP) rs2236242 was determined. The statistical analysis was performed using SPSS software version 20. Our findings showed significant age and genotype frequency differences in three groups (p-value < 0.05). There was no significant difference in vaspin levels between PTC, and control groups. The level of vaspin in MNG compared to the control group had significantly different, but there were no differences after adjustment for age. Results showed the genotypes of vaspin rs2236242 polymorphism are not associated with the level of vaspin. The genotypes and allele frequencies of vaspin rs2236242 in the PTC and MNG groups were significant compared to the control group. We have found vaspin rs2236242 gene polymorphism as a potential marker of papillary thyroid cancer. The A allele of the vaspin SNP rs2236242 plays a protective role against PTC and MNG. SNP at rs2236242 was not significantly associated with vaspin levels.

Metabolite signature of human malignant thyroid tissue: A systematic review and meta-analysis.

BACKGROUND: Thyroid cancer (TC) is the predominant malignancy within the endocrine system. However, the standard method for TC diagnosis lacks the capability to identify the pathological condition of all thyroid lesions. The metabolomics approach has the potential to manage this problem by identifying differential metabolites. AIMS: This study conducted a systematic review and meta-analysis of the NMR-based metabolomics studies in order to identify significant altered metabolites associated with TC. METHODS: A systematic search of published literature in any language in three databases including Embase, PubMed, and Scopus was conducted. Out of 353 primary articles, 12 studies met the criteria for inclusion in the systematic review. Among these, five reports belonging to three articles were eligible for meta-analysis. The correlation coefficient of the orthogonal partial least squares discriminant analysis, a popular model in the multivariate statistical analysis of metabolomic data, was chosen for meta-analysis. The altered metabolites were chosen based on the fact that they had been found in at least three studies. RESULTS: In total, 49 compounds were identified, 40 of which were metabolites. The increased metabolites in thyroid lesions compared normal samples included lactate, taurine, alanine, glutamic acid, glutamine, leucine, lysine, phenylalanine, serine, tyrosine, valine, choline, glycine, and isoleucine. Lipids were the decreased compounds in thyroid lesions. Lactate and alanine were increased in malignant versus benign thyroid lesions, while, myo-inositol, scyllo-inositol, citrate, choline, and phosphocholine were found to be decreased. The meta-analysis yielded significant results for three metabolites of lactate, alanine, and citrate in malignant versus benign specimens. DISCUSSION: In this study, we provided a concise summary of 12 included metabolomic studies, making it easier for future researchers to compare their results with the prior findings. CONCLUSION: It appears that the field of TC metabolomics will experience notable advancement, leading to the discovery of trustworthy diagnostic and prognostic biomarkers.

A global comparative analysis of the the inclusion of priority setting in national COVID-19 pandemic plans: A reflection on the methods and the accessibility of the plans.

BACKGROUND: Despite the swift governments' response to the COVID-19 pandemic, there remains a paucity of literature assessing the degree to which; priority setting (PS) was included in the pandemic plans and the pandemic plans were publicly accessible. This paper reflects on the methods employed in a global comparative analysis of the degree to which countries integrated PS into their COVID-19 pandemic plans based on Kapiriri & Martin's framework. We also assessed if the accessibility of the plans was related to the country's transparency index. METHODS: Through a three stage search strategy, we accessed and reviewed 86 national COVID-19 pandemic plans (and 11 Canadian provinces and territories). Secondary analysis assessed any alignment between the readily accessible plans and the country's transparency index. RESULTS AND CONCLUSION: 71 national plans were readily accessible while 43 were not. There were no systematic differences between the countries whose plans were readily available and those whose plans were 'missing'. However, most of the countries with 'missing' plans tended to have a low transparency index. The framework was adapted to the pandemic context by adding a parameter on the need to plan for continuity of priority routine services. While document review may be the most feasible and appropriate approach to conducting policy analysis during health emergencies, interviews and follow up document review would assess policy implementation.

Stakeholder participation in the COVID-19 pandemic preparedness and response plans: A synthesis of findings from 70 countries.

Stakeholder participation is a key component of a fair and equitable priority-setting in health. The COVID-19 pandemic highlighted the need for fair and equitable priority setting, and hence, stakeholder participation. To date, there is limited literature on stakeholder participation in the development of the pandemic plans (including the priority setting plans) that were rapidly developed during the pandemic. Drawing on a global study of national COVID-19 preparedness and response plans, we present a secondary analysis of COVID-19 national plans from 70 countries from the six WHO regions, focusing on stakeholder participation. We found that most plans were prepared by the Ministry of Health and acknowledged WHO guidance, however less than half mentioned that additional stakeholders were involved. Few plans described a strategy for stakeholder participation and/or accounted for public participation in the plan preparation. However, diverse stakeholders (including multiple governmental, non-governmental, and international organizations) were proposed to participate in the implementation of the plans. Overall, there was a lack of transparency about who participated in decision-making and limited evidence of meaningful participation of the community, including marginalized groups. The critical relevance of stakeholder participation in priority setting requires that governments develop strategies for meaningful participation of diverse stakeholders during pandemics such as COVID-19, and in routine healthcare priority setting.

Plasma metabolites analysis of patients with papillary thyroid cancer: A preliminary untargeted 1H NMR-based metabolomics.

Metabolomics plays a crucial role in identifying molecular biomarkers that can differentiate pathological conditions. In the case of thyroid cancer, it is essential to accurately diagnose malignancy from benignity to avoid unnecessary surgeries. The objective of this research was to apply untargeted NMR-based metabolomics in order to identify metabolic biomarkers that can distinguish between plasma samples of patients with papillary thyroid cancer (PTC) and multinodular goiter (MNG), as well as PTC and healthy individuals. The study included a cohort of 55 patients who were divided into three groups: PTC (n=20), MNG (n=16), and healthy (n=19). Plasma samples were collected from all participants and subjected to 1H NMR spectroscopy. Differential metabolites were identified using chemometric pattern recognition algorithms. The obtained metabolic profile had the potential to differentiate PTC from healthy plasma, but not from MNG. In patients diagnosed with PTC, a total of 18 compounds were discovered, revealing elevated levels of leucine, lysine, and 4-acetamidobutyric acid, while acetate, proline, acetoacetate, 3-hydroxybutyrate, glutamate, pyruvate, cystine, glutathione, asparagine, ethanolamine, histidine, tyrosine, myo-inositol, and glycerol along with a lipid compound were found to be lower in comparison to those of healthy individuals. According to the area under the curve (AUC) of the receiver operating characteristic curve, this particular profile exhibited an impressive capability of 85% to discern PTC from healthy subjects (AUC=0.853, sensitivity=78.95, specificity=84.21). The utilization of the 1H NMR-based metabolomics approach revealed considerable promise in the identification of PTC from healthy plasma specimens. The modifications noticed in the plasma metabolites have the potential to act as practical biomarkers that are non-invasive and could suggest transformations in the metabolic profile of thyroid tumors.

Design and fabrication of a GaN HEMT power amplifier based on hidden Markov model for wireless applications.

Improvement of power amplifier's performance is the desired topic in communication systems. There are many efforts are made to provide good input and output matching, high efficiency, sufficient power gain and appropriate output power. This paper presents a power amplifier with optimized input and output matching networks. In the proposed approach, a new structure of the Hidden Markov Model with 20 hidden states is used for modeling the power amplifier. The widths and lengths of the microstrip lines in the input and output matching networks are defined as the parameters that the Hidden Markov Model should optimize. For validating our algorithm, a power amplifier has been realized based on a 10W GaN HEMT with part number CG2H40010F from the Cree corporation. Measurement results have shown a PAE higher than 50%, a Gain of about 14 dB, and input and output return losses lower than -10 dB over the frequency range of 1.8-2.5 GHz. The proposed PA can be used in wireless applications such as radar systems.

Upper Extremity Crotalid Envenomation: A Review of Incidence and Recent Trends in Management of Snakebites.

PURPOSE: The goal of this study was to evaluate the recent trends in the management of upper extremity Crotalid envenomation in the state of Georgia, United States. METHODS: A retrospective review of the Georgia Poison Center database looking at the reported snakebites to the upper extremity between 2015 and 2020 was performed. Patient demographics, timing and location of injury, severity of envenomation, treatment, including use of antivenin and surgical intervention, and reported complications related to the use of antivenin was extracted. RESULTS: A retrospective review of snakebites between 2015 and 2020 showed 2408 snakebite cases with a mean patient age of 37.4 years. Males incurred 62.8% of all bites. The highest incidence was in summer 52.5%, and between the hours of 5 PM to midnight 57.2%. Overall, 1010 (41.9%) of all bites were categorized as venomous snakebites (55.6% copperhead, 20% rattlesnake, 2.4% cottonmouth, and 22% miscellaneous [including 3 Elapid envenomations] or unidentified. The total number of venomous bites to the upper extremity was 575 (56.9%) and 567 patients received antivenin. Envenomation severity was mild in 29%, moderate in 45%, severe in 10%, and undetermined in 16% of cases. Crotalidae polyvalent immune Fab (Ovine) was the main antivenin used, with overall mean initial therapy dose of 6.2 vials and 59% of patients receiving maintenance therapy. Three patients (0.5%) had a severe anaphylactic reaction to antivenin requiring cessation of therapy. Seven patients had acute compartment syndrome of the upper extremity requiring fasciotomy (3 copperhead, 2 rattlesnake, and 2 unidentified). There was no reported mortality during this period. CONCLUSIONS: Hand surgeons should be familiar with the management of upper extremity Crotalid envenomation. Antivenin remains the main treatment for symptomatic patients. Crotalid snakebites rarely require operative intervention. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Elevated Plasma Levels of MT4-MMP and MT6-MMP; A New Observation in Patients with Thyroid Nodules.

BACKGROUND: Based on the critical role of MT4-MMP and MT6-MMP in carcinogenesis, we focused on MT4-MMP and MT6-MMP circulating levels in patients with thyroid nodules. METHODS: Plasma samples were collected from three groups, including papillary thyroid cancer (PTC; n=30), multinodular goiter (MNG; n=30), and healthy subjects (n=22). Enzyme-linked immunosorbent assay (ELISA) was used to obtain the concentration of MT4-MMP and MT6-MMP in the three groups. RESULTS: Analysis of data demonstrated increased levels of MT4-MMP (PTC: 4.90±1.35, MNG: 4.89±1.37, and healthy: 3.13±1.42) and MT6-MMP (PTC: 8.29±2.50, MNG: 7.34±2.09, and healthy:5.01±2.13) in thyroid nodules by comparison with healthy subjects (P<0.05). There were no significant differences in the levels of the two MT-MMPs between PTC and MNG (P>0.05). Increased plasma levels of MT4-MMP (odds ratio=2.48; 95% CI: 1.46-4.19; P=0.001) or MT6-MMP (odds ratio=1.81; 95% CI: 1.29-2.53; P=0.001) were associated with increased risk of PTC tumorigenesis. Interestingly, a strong positive association was observed between MT4-MMP and MT6-MMP in the three groups (PTC: r=0.766**, P=0.000; MNG: r=0.856**, P=0.000; healthy r=0.947**, P=0.000). Areas under the ROC curve for MT4-MMP and MT6-MMP were 0.82 and 0.96, respectively. At the cutoff value>4.7 (ng/mL), MT4-MMP and MT6-MMP showed a sensitivity of 63.3% and 90.0%, respectively, with 100% specificity. CONCLUSION: Our work has led us to imply that the higher levels of MT4-MMP and MT6-MMP are closely linked with both PTC and MNG tumorigenesis. They may probably promote the development of thyroid lesions; however, more research is needed to further clarify the current findings.

Priority setting for pandemic preparedness and response: A comparative analysis of COVID-19 pandemic plans in 12 countries in the Eastern Mediterranean Region.

Background: The COVID-19 pandemic has significantly disrupted health systems and exacerbated pre-existing resource gaps in the Eastern Mediterranean Region (WHO-EMRO). Active humanitarian and refugee crises have led to mass population displacement and increased health system fragility, which has implication for equitable priority setting (PS). We examine whether and how PS was included in national COVID-19 pandemic plans within EMRO. Methods: An analysis of COVID-19 pandemic response and preparedness planning documents from a sample of 12/22 countries in WHO-EMRO. We assessed the degree to which documented PS processes adhere to twenty established quality parameters of effective PS. Results: While all reviewed plans addressed some aspect of PS, none included all quality parameters. Yemen's plan included the highest number (9) of quality parameters, while Egypt's addressed the lowest (3). Most plans used evidence in their planning processes. While no plans explicitly identify equity as a criterion to guide PS; many identified vulnerable populations - a key component of equitable PS. Despite high concentrations of refugees, migrants, and IDPs in EMRO, only a quarter of the plans identified them as vulnerable. Conclusion: PS setting challenges are exacerbated by conflict and the resulting health system fragmentation. Systematic and quality PS is essential to tackle long-term health implications of COVID-19 for vulnerable populations in this region, and to support effective PS and equitable resource allocation.

Improvement of stability and antioxidant activity of wheat germ by mixed fermentation versus single fermentation.

Wheat germ is a high-nutrient by-product from the milling industry with very limited optimal consumption due to its short shelf life. The severe activity of endogenous lipase and lipoxygenase is associated with the release of fatty acids which are responsible for the rancidity and shelf-life deficiency. Reducing these enzymes activity is essential for prolonging the wheat germ shelf-life. For this purpose, the mixed and simple fermentation of different wheat germ concentrations (10, 15 and 20% w/v wheat germ in distilled water) with Lactobacillus plantarum and Lactobacillus acidophilus was investigated to improve the stability of wheat germ by restraining the activity of the enzymes. Fermentation noticeably reduced the activity of the enzymes in all samples (ranges from 50 to 82.15% for lipase and 55.34 to 72 for lipoxygenase in different treatments), but the mixed-fermented wheat germ with the maximum concentration (20%) achieved the highest reduction level in both enzymes inactivation. Fermentation also resulted in an obvious increase in antioxidant activity from 51.18% in raw wheat germ to more than 72.73% in different samples, which mixed fermentation of 20% wheat germ suspension with the value of 89.76 was ranked first.

Equity, justice, and social values in priority setting: a qualitative study of resource allocation criteria for global donor organizations working in low-income countries.

BACKGROUND: There is increasing acceptance of the importance of social values such as equity and fairness in health care priority setting (PS). However, equity is difficult to define: the term means different things to different people, and the ways it is understood in theory often may not align with how it is operationalized. There is limited literature on how development assistance partner organizations (DAP) conceptualize and operationalize equity in their health care prioritization decisions that affect low-income countries (LIC). This paper explores whether and how equity is a consideration in DAP priority setting processes. METHODS: This was a qualitative study involving 38 in-depth interviews with DAPs involved in health-system PS for LICs and a review of their respective webpages. RESULTS: While several PS criteria were identified, direct articulation of equity as an explicit criterion was lacking. However, the criterion was implied in some of the responses in terms of prioritizing vulnerable populations. Where mentioned, respondents discussed the difficulties of operationalizing equity as a PS criterion since vulnerability is associated with several varying and competing factors including gender, age, geography, and income. Some respondents also suggested that equity could be operationalized in terms of an organization not supporting the pre-existing inequities. Although several organizations' webpages identify addressing inequities as a guiding principle, there were variations in how they spoke about its operationalization. While intersectionalities in vulnerabilities complicate its operationalization, if organizations explicitly articulate their equity focus the other organizations who also have equity as a guiding principle may, instead of focusing on the same aspect, concentrate on other dimensions of vulnerability. That way, all organizations will contribute to achieving equity in all the relevant dimensions. CONCLUSIONS: Since most development organizations support some form of equity, this paper highlights a need for an internationally recognized framework that recognizes the intersectionalities of vulnerability, for mainstreaming and operationalizing equity in DAP priority setting and resource allocation. Such a framework will support consistency in the conceptualization of and operationalization of equity in global health programs. There is a need for studies which to assess the degree to which equity is actually integrated in these programs.

Comparative analysis of protein-protein interaction networks in metastatic breast cancer.

Metastatic lesions leading causes of the majority of deaths in patients with the breast cancer. The present study aimed to provide a comprehensive analysis of the differentially expressed genes (DEGs) in the brain (MDA-MB-231 BrM2) and lung (MDA-MB-231 LM2) metastatic cell lines obtained from breast cancer patients compared with those who have primary breast cancer. We identified 981 and 662 DEGs for brain and lung metastasis, respectively. Protein-protein interaction (PPI) analysis revealed seven shared (PLCB1, FPR1, FPR2, CX3CL1, GABBR2, GPR37, and CXCR4) hub genes between brain and lung metastasis in breast cancer. Moreover, GNG2 and CXCL8, C3, and PTPN6 in the brain and SAA1 and CCR5 in lung metastasis were found as unique hub genes. Besides, five co-regulation of clusters via seven important co-expression genes (COL1A2, LUM, SPARC, THBS2, IL1B, CXCL8, THY1) were identified in the brain PPI network. Clusters screening followed by biological process (BP) function and pathway enrichment analysis for both metastatic cell lines showed that complement receptor signalling, acetylcholine receptor signalling, and gastric acid secretion pathways were common between these metastases, whereas other pathways were site-specific. According to our findings, there are a set of genes and functional pathways that mark and mediate breast cancer metastasis to the brain and lungs, which may enable us understand the molecular basis of breast cancer development in a deeper levele to the brain and lungs, which may help us gain a more complete understanding of the molecular underpinnings of breast cancer development.

Barriers to Equitable Public Participation in Health-System Priority Setting Within the Context of Decentralization: The Case of Vulnerable Women in a Ugandan District.

BACKGROUND: Decentralization of healthcare decision-making in Uganda led to the promotion of public participation. To facilitate this, participatory structures have been developed at sub-national levels. However, the degree to which the participation structures have contributed to improving the participation of vulnerable populations, specifically vulnerable women, remains unclear. We aim to understand whether and how vulnerable women participate in health-system priority setting; identify any barriers to vulnerable women's participation; and to establish how the barriers to vulnerable women's participation can be addressed. METHODS: We used a qualitative description study design involving interviews with district decision-makers (n=12), sub-county leaders (n=10), and vulnerable women (n=35) living in Tororo District, Uganda. Data was collected between May and June 2017. The analysis was conducting using an editing analysis style. RESULTS: The vulnerable women expressed interest in participating in priority setting, believing they would make valuable contributions. However, both decision-makers and vulnerable women reported that vulnerable women did not consistently participate in decision-making, despite participatory structures that were instituted through decentralization. There are financial (transportation and lack of incentives), biomedical (illness/disability and menstruation), knowledge-based (lack of knowledge and/or information about participation), motivational (perceived disinterest, lack of feedback, and competing needs), socio-cultural (lack of decision-making power), and structural (hunger and poverty) barriers which hamper vulnerable women's participation. CONCLUSION: The identified barriers hinder vulnerable women's participation in health-system priority setting. Some of the barriers could be addressed through the existing decentralization participatory structures. Respondents made both short-term, feasible recommendations and more systemic, ideational recommendations to improve vulnerable women's participation. Integrating the vulnerable women's creative and feasible ideas to enhance their participation in health-system decision-making should be prioritized.

Priority setting and equity in COVID-19 pandemic plans: a comparative analysis of 18 African countries.

Priority setting represents an even bigger challenge during public health emergencies than routine times. This is because such emergencies compete with routine programmes for the available health resources, strain health systems and shift health-care attention and resources towards containing the spread of the epidemic and treating those that fall seriously ill. This paper is part of a larger global study, the aim of which is to evaluate the degree to which national COVID-19 preparedness and response plans incorporated priority setting concepts. It provides important insights into what and how priority decisions were made in the context of a pandemic. Specifically, with a focus on a sample of 18 African countries' pandemic plans, the paper aims to: (1) explore the degree to which the documented priority setting processes adhere to established quality indicators of effective priority setting and (2) examine if there is a relationship between the number of quality indicators present in the pandemic plans and the country's economic context, health system and prior experiences with disease outbreaks. All the reviewed plans contained some aspects of expected priority setting processes but none of the national plans addressed all quality parameters. Most of the parameters were mentioned by less than 10 of the 18 country plans reviewed, and several plans identified one or two aspects of fair priority setting processes. Very few plans identified equity as a criterion for priority setting. Since the parameters are relevant to the quality of priority setting that is implemented during public health emergencies and most of the countries have pre-existing pandemic plans; it would be advisable that, for the future (if not already happening), countries consider priority setting as a critical part of their routine health emergency and disease outbreak plans. Such an approach would ensure that priority setting is integral to pandemic planning, response and recovery.

New evidence on tumor suppressor activity of PTEN and KLLN in papillary thyroid carcinoma.

This study aimed to address the hypothesis that the expression of PTEN and KLLN tumor suppressor genes could diminish in papillary thyroid cancer (PTC) compared to paired normal tissue (PNT) and multinodular goiter (MNG). PTEN and KLLN expressions were assessed at both mRNA and protein levels in 82 tissue samples, including 30 PTC, 30 PNT, and 26 MNG using SYBR-Green Real-Time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Bioinformatics studies were performed to evaluate the genomic location and the genes promoter region. The mRNA expression of PTEN and KLLN in PTC was significantly lower than PNT (PTEN, P = 0.0033; KLLN, P = 0.0005). A significant decrease in the mRNA level of KLLN was also observed in PTC than MNG (P = 0.0304). Decreased level of PTEN mRNA (odds ratio=0.391; P = 0.013) or KLLN mRNA (odds ratio=0.023; P = 0.025) was associated with an increased risk of PTC tumorigenesis. Areas under the ROC curve for PTEN and KLLN were 0.69 and 0.78, respectively. PTEN and KLLN protein expressions in PTC compared to PNT or MNG were not significantly different. The bioinformatics studies revealed the sequence near the promoter region is lowly conserved across species. Four GC boxes were found upstream of the PTEN transcription start site (TSS), and one TATA box and one GC box were found upstream of KLLN TSS. The results suggest PTEN and KLLN are the two tumor suppressor genes that decreasing or loss of both of them occurs in sporadic PTC tumorigenesis. It appears they could have a promising application in both diagnostic and therapeutic areas.

Ischemic Complications After Bilateral Nipple-sparing Mastectomy and Implant-based Reconstruction: A Critical Analysis.

PURPOSE: Nipple-sparing mastectomy (NSM) has a higher incidence of mastectomy skin flap necrosis (MSFN) than skin-sparing mastectomy. The purpose of this study is to analyze predisposing factors for nipple and skin necrosis after bilateral NSM with immediate implant reconstruction. METHODS: Sixty-two consecutive patients (124 breasts) from a single breast/plastic surgeon underwent bilateral NSM with immediate implant-based breast reconstruction were included. Factors influencing MSFN were analyzed. RESULTS: The mean age was 45.7 years, and mean body mass index was 22.9. Reconstructive methods were as follows: tissue expander (TE), 76 (61.3%); and direct to implant, 48 (38.7%). Mastectomy skin flap necrosis occurred in 39 (31.5%) breasts, nipple necrosis 38 and skin flap necrosis 19. Thirty-seven breasts healed uneventfully, and 2 (1.6%) required reoperation. Cancer pathology, mastectomy weight greater than 279 g, TE reconstruction, and nipple-notch (N-N) distance greater than 23 cm were predictive of nipple necrosis on univariate analysis. The mean mastectomy weight (380.1 g vs 220.7 g, P < 0.0001), N-N distance greater than 23 cm (30 vs 0, P < 0.0001), and mean implant size (490 cm3 vs 373 cm3, P < 0.0001) were greater in the TE group. On logistic regression model controlling for all significant variables, predictors of MSFN were as follows: diagnosis of cancer (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.41-8.03; P = 0.006), TE reconstruction (OR, 2.87; 95% CI, 1.03-8.03; P = 0.04), and N-N distance (OR, 1.31; 95% CI, 1.03-1.66; P = 0.03). CONCLUSIONS: Mastectomy skin flap necrosis after NSM and implant reconstruction is common. In this series, only 2 (1.6%) cases required surgical intervention with no implant loss. Treatment of breast cancer, TE reconstruction, and increasing N-N notch distance were positive predictors of MSFN.