Background: Cerebral vasospasm has been reported following various forms of bacterial meningitis; however, there have been no prior reports of meningitis caused by the non-K1 strain of Escherichia coli. Case Report: A 63-year-old man with chronic thrombocytopenia presented with new-onset seizures that progressed to coma. Cerebrospinal fluid (CSF) analysis showed Gram-negative rods, but CSF culture and the Biofire FilmArray Meningitis/Encephalitis Panel were negative. Additional 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction and sequencing of the CSF sample indicated E. coli meningitis when correlated with the results of urine culture. The patient eventually developed diffuse cerebral arterial vasospasms with multifocal brain infarcts that progressed to brain death. Conclusion E. coli meningitis in adults may be missed if diagnostic tests include only K1 strains. Clinicians should be aware of cerebral vasospasm as a potentially serious complication of E. coli meningitis, and should consider screening for it, particularly in patients with associated risk factors.

Objective: The Cancer Genome Atlas study revealed an association between copy-number high (p53 abnormal) genetic mutation and poor prognosis in endometrial cancer in 2013.This retrospective study investigated outcomes in patients with abnormal p53 expression and stage I, low-grade endometrial endometrioid carcinoma (EEC). Methods: We enrolled women with stage I, grade 1 or 2 EEC who received comprehensive staging and adjuvant therapy between January 2019 and December 2022 at MacKay Memorial Hospital, Taipei, Taiwan. Pathologists interpreted immunohistochemistry stains of cancerous tissues to detect p53 mutation. We compared recurrence, survival, progressionfree survival, and overall survival between p53 abnormal and p53 normal groups. Results: Of the 115 patients included, 26 had pathologically confirmed abnormal p53 expression. Of these 26 patients, five (19.2%) experienced recurrence, and two died due to disease progression. By contrast, no patients in the normal p53 group experienced disease recurrence or died due to disease progression. Significant intergroup differences were discovered in recurrent disease status (19.4% vs. 0%, p<0.001), mortality (7.7% vs.0%, p<0.001), and progression-free survival (p<0.001). The overall survival (p=0.055) also showed powerful worse trend. Conclusion For patients with stage I, low-grade EEC, abnormal p53 expression may be used as an indicator of poor prognosis. Therefore, we suggest considering aggressive adjuvant therapies for these patients.

Objective: The Cancer Genome Atlas study revealed an association between copy-number high (p53 abnormal) genetic mutation and poor prognosis in endometrial cancer in 2013.This retrospective study investigated outcomes in patients with abnormal p53 expression and stage I, low-grade endometrial endometrioid carcinoma (EEC). Methods: We enrolled women with stage I, grade 1 or 2 EEC who received comprehensive staging and adjuvant therapy between January 2019 and December 2022 at MacKay Memorial Hospital, Taipei, Taiwan. Pathologists interpreted immunohistochemistry stains of cancerous tissues to detect p53 mutation. We compared recurrence, survival, progressionfree survival, and overall survival between p53 abnormal and p53 normal groups. Results: Of the 115 patients included, 26 had pathologically confirmed abnormal p53 expression. Of these 26 patients, five (19.2%) experienced recurrence, and two died due to disease progression. By contrast, no patients in the normal p53 group experienced disease recurrence or died due to disease progression. Significant intergroup differences were discovered in recurrent disease status (19.4% vs. 0%, p<0.001), mortality (7.7% vs.0%, p<0.001), and progression-free survival (p<0.001). The overall survival (p=0.055) also showed powerful worse trend. Conclusion For patients with stage I, low-grade EEC, abnormal p53 expression may be used as an indicator of poor prognosis. Therefore, we suggest considering aggressive adjuvant therapies for these patients.

Background: Cerebral vasospasm has been reported following various forms of bacterial meningitis; however, there have been no prior reports of meningitis caused by the non-K1 strain of Escherichia coli. Case Report: A 63-year-old man with chronic thrombocytopenia presented with new-onset seizures that progressed to coma. Cerebrospinal fluid (CSF) analysis showed Gram-negative rods, but CSF culture and the Biofire FilmArray Meningitis/Encephalitis Panel were negative. Additional 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction and sequencing of the CSF sample indicated E. coli meningitis when correlated with the results of urine culture. The patient eventually developed diffuse cerebral arterial vasospasms with multifocal brain infarcts that progressed to brain death. Conclusion E. coli meningitis in adults may be missed if diagnostic tests include only K1 strains. Clinicians should be aware of cerebral vasospasm as a potentially serious complication of E. coli meningitis, and should consider screening for it, particularly in patients with associated risk factors.

Objective: The Cancer Genome Atlas study revealed an association between copy-number high (p53 abnormal) genetic mutation and poor prognosis in endometrial cancer in 2013.This retrospective study investigated outcomes in patients with abnormal p53 expression and stage I, low-grade endometrial endometrioid carcinoma (EEC). Methods: We enrolled women with stage I, grade 1 or 2 EEC who received comprehensive staging and adjuvant therapy between January 2019 and December 2022 at MacKay Memorial Hospital, Taipei, Taiwan. Pathologists interpreted immunohistochemistry stains of cancerous tissues to detect p53 mutation. We compared recurrence, survival, progressionfree survival, and overall survival between p53 abnormal and p53 normal groups. Results: Of the 115 patients included, 26 had pathologically confirmed abnormal p53 expression. Of these 26 patients, five (19.2%) experienced recurrence, and two died due to disease progression. By contrast, no patients in the normal p53 group experienced disease recurrence or died due to disease progression. Significant intergroup differences were discovered in recurrent disease status (19.4% vs. 0%, p<0.001), mortality (7.7% vs.0%, p<0.001), and progression-free survival (p<0.001). The overall survival (p=0.055) also showed powerful worse trend. Conclusion For patients with stage I, low-grade EEC, abnormal p53 expression may be used as an indicator of poor prognosis. Therefore, we suggest considering aggressive adjuvant therapies for these patients.

Background: Cerebral vasospasm has been reported following various forms of bacterial meningitis; however, there have been no prior reports of meningitis caused by the non-K1 strain of Escherichia coli. Case Report: A 63-year-old man with chronic thrombocytopenia presented with new-onset seizures that progressed to coma. Cerebrospinal fluid (CSF) analysis showed Gram-negative rods, but CSF culture and the Biofire FilmArray Meningitis/Encephalitis Panel were negative. Additional 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction and sequencing of the CSF sample indicated E. coli meningitis when correlated with the results of urine culture. The patient eventually developed diffuse cerebral arterial vasospasms with multifocal brain infarcts that progressed to brain death. Conclusion E. coli meningitis in adults may be missed if diagnostic tests include only K1 strains. Clinicians should be aware of cerebral vasospasm as a potentially serious complication of E. coli meningitis, and should consider screening for it, particularly in patients with associated risk factors.

The spleen is the largest lymphoid organ that can affect the immunological microenvironment in the liver via the portal system. Patients with liver cancer, often develop hypersplenism and splenomegaly from underlying cirrhosis and portal hypertension. The malfunction of the spleen not only induces hepatic fibrogenesis, but also changes the immune responses in the liver, so that liver cirrhosis accelerates while liver regeneration subdues. As a result, the hepatic microenvironment and the rest of the immune system reach a “tumor progressing” or “tumor tolerant” state. Splenectomy has been shown to improve immune responses, liver function and general condition in patients with liver cancer. Hence, splenectomy may possibly improve the tolerance in live cancer patients for other anticancer treatments. However, the long-term benefits and effects on the overall survival of concomitant hepatectomy and splenectomy for liver cancer patients with portal hypertension and hypersplenism still remain controversial.

Mutations in genes encoding amyloid precursor protein (APP) and presenilins (PSs) cause familial forms of Alzheimer's disease (AD), a neurodegenerative disorder strongly associated with aging. It is currently unknown whether and how AD risks affect early brain development, and to what extent subtle synaptic pathology may occur prior to overt hallmark AD pathology. Transgenic mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD pathogenesis. Among these lines, the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloid β (Aβ)-induced neurodegeneration. We reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons, and performed detailed synaptic physiological characterization of layer 5 (L5) neurons from the prefrontal cortex (PFC) of 5XFAD and wild-type littermate controls. L5 PFC neurons from 5XFAD mice show early APP/Aβ immunolabeling. Whole-cell patch-clamp recording at an early post-weaning age (P22-30) revealed functional impairments; although 5XFAD PFC-L5 neurons exhibited similar membrane properties, they were intrinsically less excitable. In addition, these neurons received smaller amplitude and frequency of miniature excitatory synaptic inputs. These functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse maturation. Slice biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit GluN2A. Consistent with this, patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio, and an increased level of AMPAR-lacking silent synapses. These results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early developmental defects of cortical circuits, which could contribute to the age-dependent synaptic pathology and neurodegeneration later in life.
Mice ; Animals ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Neurons/metabolism* ; Receptors, AMPA/metabolism* ; Disease Models, Animal

Despite tremendous efforts to fight cancer,it remains a major public health problem and a leading cause of death worldwide.With increased knowledge of cancer pathways and improved technological platforms,precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes.Nevertheless,a primary cause of unsuccessful cancer therapy remains cancer drug resistance.In this review,we summarize the broad classes of resistance to cancer therapy,particularly pharmacokinetics,the tumor microenvironment,and drug resistance mechanisms.Furthermore,we describe how bacterial-mediated cancer therapy,a bygone mode of treatment,has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies.Through genetic engineering,we discuss how bacteria can be potent anticancer agents given their tumor targeting potential,anti-tumor activity,safety,and coordinated delivery of anti-cancer drugs.

Despite tremendous efforts to fight cancer,it remains a major public health problem and a leading cause of death worldwide.With increased knowledge of cancer pathways and improved technological platforms,precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes.Nevertheless,a primary cause of unsuccessful cancer therapy remains cancer drug resistance.In this review,we summarize the broad classes of resistance to cancer therapy,particularly pharmacokinetics,the tumor microenvironment,and drug resistance mechanisms.Furthermore,we describe how bacterial-mediated cancer therapy,a bygone mode of treatment,has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies.Through genetic engineering,we discuss how bacteria can be potent anticancer agents given their tumor targeting potential,anti-tumor activity,safety,and coordinated delivery of anti-cancer drugs.