Endometrioid Adenocarcinoma With "Burrowing" Invasion of the Cervix Represents a Separate Primary From the Concurrent Uterine Corpus Endometrial Endometrioid Adenocarcinoma: Histology, Immunohistochemistry, and Next-generation Sequencing Study of a Single Case.

A small subset of endometrial endometrioid adenocarcinoma cases first reported in 2003, showed a distinct cervical component with a so-called "burrowing" invasion pattern. Initially, the cervical component was regarded as cervical involvement by the endometrial adenocarcinoma. However, a 2010 study argued that these cases actually might represent separate primary endometrial and cervical endometrioid adenocarcinomas. However, additional data on this topic are scarce. Here, we report a case of endometrioid adenocarcinoma with a "burrowing" cervical invasion that is morphologically distinct from the patient's endometrial endometrioid adenocarcinoma. By comparing the morphology, immunophenotype, and genetic profile obtained by next-generation sequencing, we demonstrated that the cervical and endometrial tumors were of 2 separate primaries. Our report adds additional data to this unique phenomenon, and will hopefully help to reignite interest in investigating this controversial topic.

Structure-activity relationship of the aminomethylcyclines and the discovery of omadacycline.

A series of novel tetracycline derivatives were synthesized with the goal of creating new antibiotics that would be unaffected by the known tetracycline resistance mechanisms. New C-9-position derivatives of minocycline (the aminomethylcyclines [AMCs]) were tested for in vitro activity against Gram-positive strains containing known tetracycline resistance mechanisms of ribosomal protection (Tet M in Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae) and efflux (Tet K in S. aureus and Tet L in E. faecalis). A number of aminomethylcyclines with potent in vitro activity (MIC range of ≤0.06 to 2.0 µg/ml) were identified. These novel tetracyclines were more active against one or more of the resistant strains than the reference antibiotics tested (MIC range, 16 to 64 µg/ml). The AMC derivatives were active against bacteria resistant to tetracycline by both efflux and ribosomal protection mechanisms. This study identified the AMCs as a novel class of antibiotics evolved from tetracycline that exhibit potent activity in vitro against tetracycline-resistant Gram-positive bacteria, including pathogenic strains of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE). One derivative, 9-neopentylaminomethylminocycline (generic name omadacycline), was identified and is currently in human trials for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP).

KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss.

Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.

Are the relationships between mental health issues and being left-behind gendered in China: A systematic review and meta-analysis.

BACKGROUND: While most existing studies reveal left-behind children (LBC) are prone to suffering from mental health issues, some other literature fails to develop a statistical significance between being left-behind and facing mental health dilemmas. In further detail, it is noteworthy that suicide ideation is a gendered issue. Here girls, relative to their male counterparts, are more likely to experience emotional and affective challenges, alongside a higher risk of suicide ideation. Aside from suicide ideation, the rate of suicide attempts is also higher among Chinese female than among male LBC. However, Chang et al. counter-argue that, within the LBC cohorts, it is not statistically significant to state that girls were more likely for suicide attempts than boys. METHODS: In this paper, a systematic review of relevant literature and a meta-analysis of all qualified randomised controlled trial (RCT) studies were conducted. The authors aim to examine all relevant studies with similar methodologies to observe the nuanced relationships between being left-behind and mental health issues in Chinese contexts. Specifically, the authors will, grounded on the findings from the systematic review and meta-analysis, assess whether the relationship between mental health issues and being left-behind is gendered in Chinese contexts by analysing all relevant findings derived from similar methodologies and the same method (i.e., RCT). RESULTS: Aside from Wanjie et al.'s studies, it is noticeable that the rest of the studies share similar point estimates and their CIs overlapped to a large extent. As per the I2, given the presence of Wanjie et al.'s studies that demonstrate an observably higher degree of heterogeneity than the rest of the studies, the I2 values, each for the measurement of anxiety and depression, are 74.8 percent and 34.7 percent respectively. This shows that there is a considerable heterogeneity level for anxiety, while the heterogeneity level for depression is moderate. However, both p-values for the I2 statistics are larger than 0.05. Therefore, at the 0.05 significance level, it is statistically insignificant to reject the null hypothesis that there is no heterogeneity between individual studies in both the subgroups of anxiety and depression. Therefore, the concern of the potentially substantial heterogeneity should be irrelevant in this meta-analysis. Beyond the discussion from the forest plot, when looking at the single study addressing the relationship between being left-behind and having suicide attempts (note: LBC-OR is 1.22; 95 percent CI is 1.22 -and NLBC-OR is 1.42; 95 percent CI is 1.09-1.86 -at the p-value of 0.34), the findings demonstrate that such a relationship per se is not gendered at the 0.05 statistical significance level. However, when examining the relationship between being resilient and left-behind, such an association is gendered where the OR of female left-behind university students being resilient, relative to male left-behind university students, is slightly higher than that of female non-left-behind university students being resilient, relative to their male non-left-behind university student counterparts. It is noteworthy that this study focuses on studying left-behind and non-left-behind samples who entered universities. Since a raft of LBC are socially, educationally disadvantaged, they lack the opportunities to receive higher education. Therefore, the findings of this study might not be indicative of the LBC population at large. CONCLUSIONS: While the findings of this meta-analysis project fail to reflect any gendered issues statistically, the authors are aware of the fact that the data included in this project were collected based on perception. Here samples, or their parents and teachers, were responsible for answering the questions with respect to samples' mental health status and demographic details. In China, especially in less developed rural regions, the discourse on mental health challenges might continue to be seen as taboo, so individuals giving responses might, consciously or not, tend to give socially desirable answers to avoid any potential social stigmatisation. Therefore, there is some extent of reservation regarding the validity of the included studies' data.

Neuronal Glycogen Breakdown Mitigates Tauopathy via Pentose Phosphate Pathway-Mediated Oxidative Stress Reduction.

Tauopathies encompass a range of neurodegenerative disorders, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). Unfortunately, current treatment approaches for tauopathies have yielded limited success, underscoring the pressing need for novel therapeutic strategies. We observed distinct signatures of impaired glycogen metabolism in the Drosophila brain of the tauopathy model and the brain of AD patients, indicating a link between tauopathies and glycogen metabolism. We demonstrate that the breakdown of neuronal glycogen by activating glycogen phosphorylase (GlyP) ameliorates the tauopathy phenotypes in flies and induced pluripotent stem cell (iPSC) derived neurons from FTD patients. We observed that glycogen breakdown redirects the glucose flux to the pentose phosphate pathway to alleviate oxidative stress. Our findings uncover a critical role for increased GlyP activity in mediating the neuroprotection benefit of dietary restriction (DR) through the cAMP-mediated protein kinase A (PKA) activation. Our studies identify impaired glycogen metabolism as a key hallmark for tauopathies and offer a promising therapeutic target in tauopathy treatment.

KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss.

Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we define a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIdney/BRAin (KIBRA) protein (CT-KIBRA). We show that CT-KIBRA restores plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we find that CT-KIBRA binds to and stabilizes protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. In humans we find that reduced KIBRA in brain and increased KIBRA in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. Thus, our results distinguish KIBRA both as a novel biomarker of synapse dysfunction in AD and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.