Patient Selection for Living Donor Liver Transplantation in Acute-on-chronic Liver Failure.

Background and objectives: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality without liver transplantation (LT). The selection criteria for LT in these patients are not well defined. The objective of this study was to determine factors associated with post-transplant survival in ACLF. Methods: This was a single-center retrospective study of patients who underwent living donor liver transplantation (LDLT) for ACLF between 2012 and 2022. Out of 1093 transplants, 110 patients had underlying ACLF, based on the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. We looked at factors associated with 1-year posttransplant survival. Results: The median model for end-stage liver disease (MELD) score was 33.5 (31-38), and the 1-year posttransplant survival was 72%. Six risk factors were associated with posttransplant survival, namely, body mass index > 30 kg/m2 [HR, 4.4; 95% CI, 1.8-10.7], platelet count < 66,000/µl [HR, 2.91; CI,1.2-6.6], poor response to medical treatment [HR, 2.6; CI, 1.1-5.7], drug-resistant bacterial or fungal cultures [HR, 4.2; CI, 1.4-12.4], serum creatinine > 2.5 mg/dl [HR, 3.4; CI, 1.5-7.7], and graft-to-recipient weight ratio < 0.7 [HR, 4.8; CI, 1.4-16.3]. The 1-year post-transplant survival was 84% in patients with 0-2 risk factors (n = 89) and was 6% with 3 risk factors (n = 15) (P < 0.001). For 1-year posttransplant survival, the area under curve (AUC) for the current model was 0.8 (0.69-0.9). The AUC for CLIF-ACLF, Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and EASL-CLIF ACLF grades was < 0.5. Conclusion: In LT for ACLF, acceptable survival can be achieved when less than three high-risk factors are present.

Longitudinal tracking of intrabreath respiratory impedance in preschool children.

BACKGROUND: Longitudinal measurements of intrabreath respiratory impedance (Zrs) in preschool-aged children may be able to distinguish abnormal lung function trajectories in children with a history of wheezing compared to healthy ones. METHODS: Children from a prospective, longitudinal community-based cohort performed annual intrabreath oscillometry (IB-OSC) measurements from age 3- to 7-years. IB-OSC was performed using a single 10 Hz sinusoid while clinically asymptomatic. Linear mixed-effects models were developed to explore the effects of wheezing phenotypes, growth, and sex on seven IB-OSC outcome variables over time: resistance at end-expiration (ReE), resistance at end-inspiration (ReI), the tidal change in resistance (∆R=ReE-ReI), reactance at end-expiration (XeE), reactance at end-inspiration (XeI), the tidal change in reactance (∆X=XeE-XeI), and ∆X normalized by tidal volume (∆X/VT). RESULTS: Eighty-five children produced 374 acceptable IB-OSC measurements. Subjects were classified into one of three wheeze groups: never (n = 36), transient (n = 34), or persistent (n = 15). After adjusting for height, children with persistent wheezing, compared to those who never wheezed, had +0.814 hPa s L-1 ReE (95% confidence interval [CI] +0.178 to +1.451, p = 0.015), -0.792 hPa s L-1 XeE (95% CI -1.203 to -0.381, p = 0.003), -0.538 hPa s L-1 ∆X (95% CI -0.834 to -0.242, p = 0.007) and -1.672 hPa s L-2 ∆X/VT (95% CI -2.567 to -0.777, p < 0.001). Increasing height had a significant effect on all IB-OSC resistance and reactance variables when adjusted for the effect of preschool wheezing. CONCLUSIONS: IB-OSC is feasible for tracking lung function growth in preschool-aged children and may allow abnormal lung function to be identified early in asymptomatic preschoolers with a history of persistent wheezing.

Macroprolactin over time: Is there any point in rechecking it in people with a persistently elevated serum prolactin?

OBJECTIVE AND DESIGN: Macroprolactinemia may influence the interpretation of serum prolactin levels-a recognised phenomenon since 1981. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation) varied by analysing serial measurements in hyperprolactinaemic individuals over a period of 9 years. PATIENTS AND MEASUREMENTS: Results from 1810 individuals were included. All serum total prolactin results (measured using Roche Cobas 8000 analyser) were extracted from the laboratory information system for the period 1 January 2012 to 1 April 2021, along with relevant patient demographic/test data. Samples with a macroprolactin screening test performed (on samples with prolactin > 700 miu/L) were included in the main analysis. RESULTS: During the study period, 2782 macroprolactin checks were performed (12.5% of all prolactin tests) in 1810 individuals (599 males/2183 females, median-age: 35, interquartile range: 25-47, range: 16-93 years). Multiple macroprolactin checks were carried out on 465 patients (1437 measurements) with 94 patients (141 measurements) screening positive (<60% recovery). Only 19 patients (18 female) had at least one result above and one below the 60% screening cut-off, with 10 of these patients having results close to the 60% cut-off; in 9 patients, results were clearly different between repeat samples. In seven cases, the adjusted monomeric prolactin showed a potentially clinically significant difference. CONCLUSIONS: In this study, only 19/465 patients appeared to change macroprolactin status based on a 60% PEG recovery cut-off. The majority of these 19 patients were on antipsychotic/antidepressant medication(s) or had a prolactinoma; in only 7 did monomeric prolactin change significantly. This suggests that once macroprolactin status has been determined, clinical decision making is rarely affected by repeating it.

The Effects of poly-GA and poly-PR C9orf72 Dipeptide Repeats on Sleep Patterns in Drosophila melanogaster.

C9orf72 is the most common familial gene associated with amyotrophic lateral sclerosis (ALS). Dipeptide repeats (DPRs) encoded by an expanded nucleotide repeat sequence in the C9orf72 gene were found in the sleep-related neurons of patients, indicating a role of DPRs in ALS-associated sleep disruptions. Poly-GA or poly-PR DPRs were expressed in male Drosophila melanogaster to study their effect on sleep . Poly-PR expression caused sleep disruptions while poly-GA expression did not. This study validates the use of Drosophila as an in vivo model system for exploring the roles of DPRs in perturbing the underlying molecular mechanisms in sleep regulation.

Prevalence of dual sensory impairment in veterans: a rapid systematic review.

Dual sensory impairment (DSI) is prevalent in the older population, but due to exposure to military-related risk factors, it is a particular problem for veterans, older and younger. This rapid review aimed to critically review and summarise the prevalence of DSI in military veteran populations, as well as any associative factors and outcomes that were assessed. This was done in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. Several databases (Scopus, Web of Science, AMED, CINAHL Plus, Ultimate, and MEDLINE via EBSCOHost) were searched and five studies were selected for final review. All studies provided a prevalence rate for DSI in a veteran sample. One study also looked at functional independence as an outcome. Three of the studies considered blast injuries and traumatic brain injury (TBI) by using samples from TBI patient populations. Overall, results of this review suggest that age and presence of TBI and/or exposure to blast may increase prevalence of DSI in veterans. Prevalence rates ranged from 5.0-34.6% but there are caveats. There is a lack of universal or standardised definition for DSI, making it difficult to determine true prevalence. Future research should also include veterans who may not be receiving support from Veterans Affairs, consider factors such as TBI aetiology and severity based on clinical measures, and utilise a more standardised definition for DSI based on clinical measures.

Interpretable deep learning model for major depressive disorder assessment based on functional near-infrared spectroscopy.

BACKGROUND: Major depressive disorder (MDD) affects a substantial number of individuals worldwide. New approaches are required to improve the diagnosis of MDD, which relies heavily on subjective reports of depression-related symptoms. AIM: Establish an objective measurement and evaluation of MDD. METHODS: Functional near-infrared spectroscopy (fNIRS) was used to investigate the brain activity of MDD patients and healthy controls (HCs). Leveraging a sizeable fNIRS dataset of 263 HCs and 251 patients with MDD, including mild to moderate MDD (mMDD; n = 139) and severe MDD (sMDD; n = 77), we developed an interpretable deep learning model for screening MDD and staging its severity. RESULTS: The proposed deep learning model achieved an accuracy of 80.9% in diagnostic classification and 78.6% in severity staging for MDD. We discerned five channels with the most significant contribution to MDD identification through Shapley additive explanations (SHAP), located in the right medial prefrontal cortex, right dorsolateral prefrontal cortex, right superior temporal gyrus, and left posterior superior frontal cortex. The findings corresponded closely to the features of haemoglobin responses between HCs and individuals with MDD, as we obtained a good discriminative ability for MDD using cortical channels that are related to the disorder, namely the frontal and temporal cortical channels with areas under the curve of 0.78 and 0.81, respectively. CONCLUSION: Our study demonstrated the potential of integrating the fNIRS system with artificial intelligence algorithms to classify and stage MDD in clinical settings using a large dataset. This approach can potentially enhance MDD assessment and provide insights for clinical diagnosis and intervention.

Safety and Efficacy of Powered Non-Thermal Endoscopic Resection Device for Removal of Colonic Polyps: A Systematic Review and Meta-Analysis.

Background: Endoscopic mucosal resection is a frequently employed method for removing colonic polyps. Nonetheless, the recurrence of these polyps over a healed submucosal base can complicate the extraction of leftover lesions through standard procedures. EndoRotor®, a non-thermal device specifically designed for endoscopic mucosal resection, has recently been assessed for its utility in removing colonic polyps, non-dysplastic Barrett's esophagus, and pancreatic necrosis. We conducted a systematic review and meta-analysis to ascertain the safety and efficacy of EndoRotor® in resecting scared or recurrence colonic polyps. Methods: We conducted an exhaustive review of existing literature using databases such as Medline, Embase, Web of Science, and the Cochrane Library until January 2023. Our aim was to find all studies that assessed the safety of non-thermal endoscopic resection devices in removing colonic polyps. The primary outcome we focused on was the rate of technical success. Secondary outcomes that we considered included the frequency of remaining lesions and instances of adverse events. To analyze these data, we used comprehensive meta-analysis software. Results: Our analysis incorporated three studies comprising 54 patients who underwent resection of 60 lesions. The combined technical success rate was 93.9% (95% confidence interval (CI): 77.7-98.6%, I2 = 25.5%). In patients who had another endoscopic examination, 20 were found to have a residual lesion. After the initial session, the combined rate of remaining lesions was 39.8% (95% CI: 15.3-70.8%, I2 = 74.5%). There were eight occurrences of intraoperative bleeding and four instances of bleeding post-procedure. The combined rate of intraoperative bleeding was 13.2% (95% CI: 6.7-24.3%, I2 = 0%), and post-procedure bleeding stood at 8.5% (95% CI: 3.4-19.8%, I2 = 0%). Only one major bleeding event was recorded, and no cases of perforation were reported. Conclusion: Our research indicates that the EndoRotor® effectively removes scarred colonic polyps, though the rate of remaining lesions is significant, potentially necessitating several sessions for a thorough removal. There is a need for broader prospective studies, mainly randomized controlled trials, to further assess EndoRotor®'s efficiency and safety in eliminating colonic polyps.

Small molecular exogenous modulators of active forms of MMPs.

Matrix metalloproteinases (MMPs) are endopeptidases, and their activity depends on calcium and zinc metal ions. These enzymes are expressed originally in zymogenic form, where the active site of proteins is closed by a prodomain which is removed during activation. A homeostatic balance of their activity is primarily regulated by a 'cysteine switch' located on a consensus sequence of the prodomain and natural endogenous inhibitors, called tissue inhibitors of metalloproteinases (TIMPs). Breakage of this homeostasis may lead to various pathological conditions, which may require further activation and/or inhibition of these enzymes to regenerate that balance. Here, we report four modulators, more specifically, three inhibitors (I1, I2 and I3), and one exogenous activator (L) of the active form of human collagenase MMP-1 (without prodomain). The results were confirmed by binding studies using fluorescence-based enzyme assays.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. EVIDENCE ACQUISITION: We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. EVIDENCE SYNTHESIS: The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. CONCLUSIONS: Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Differentiating people with schizophrenia from healthy controls in a developing Country: An evaluation of portable functional near infrared spectroscopy (fNIRS) as an adjunct diagnostic tool.

Introduction: This study aimed to evaluate portable functional near-infrared spectroscopy (fNIRS) device as an adjunct diagnostic tool in Vietnam to assess hemodynamics when people with schizophrenia and healthy controls performed cognitive tasks. Methods: One hundred fifty-seven participants were divided into schizophrenia (n = 110) and healthy controls group (n = 47), which were recruited by match of age, and gender. Hemodynamic responses in the frontal cortex were monitored with a 48-channel portable device during the Stroop Color-Word Test (SCWT) and Verbal Fluency Test (VFT). General linear model compared the differences in oxyhemoglobin (HbO2) levels between the two groups. The Receiver Operating Characteristic (ROC) graph was generated for each neuroanatomical area. Results: People with schizophrenia did not show significant activation in the frontal lobe during the SCWT and VFT as compared to pre-task. During the VFT, the area under the ROC curve of the bilateral dorsolateral prefrontal cortex, bilateral orbitofrontal cortex, bilateral frontopolar prefrontal cortex, and bilateral ventrolateral prefrontal cortex were greater than 0.7 (p < 0.001). The area under the ROC curve (AUC) for the right orbitofrontal cortex was maximal during the VFT (AUC = 0.802, 95%CI = 0.731-0.872). The Youden's index reached a peak (0.57) at the optimal cut-point value (HbO2 cutoff <0.209 µmol/ml for schizophrenia) in which the sensitivity was 85%; specificity was 72%; positive predictive value (PPV) was 0.88; negative predictive value (NPV) was 0.68 and correct classification rate was 76%. Discussion: Assessing hemodynamics during VFT by portable fNIRS offers the potential as an adjunct diagnostic tool for schizophrenia in developing countries.

Utility of portable functional near-infrared spectroscopy (fNIRS) in patients with bipolar and unipolar disorders: A comparison with healthy controls.

BACKGROUND: This study aimed to evaluate portable functional near-infrared spectroscopy (fNIRS) device as an adjunct diagnostic tool for bipolar and unipolar disorders while performing cognitive tasks. METHODS: 150 participants were divided into three groups including bipolar, unipolar disorder, and healthy controls (50:50:50), matched by age, gender, and family history of mood disorder. Hemodynamics in the frontal cortex were monitored by fNIRS during the Stroop Color-Word Test and Verbal Fluency Test. The GLM compared the differences in oxy-hemoglobin levels between the two groups. The Receiver Operating Characteristic (ROC) graph was generated for each neuroanatomical area. RESULTS: For people with BD group, the area under the ROC curve (AUC) for the left orbitofrontal cortex was maximal during the VFT [AUC = 0.727, 95%CI = 0.617-0.824]. The Youden's index reached a peak (0.40) at the optimal cut-point value (HbO2 cutoff <0.180 µmol/ml for BD) in which the sensitivity was 82 %; specificity was 58 %; PPV was 0.66; NPV was 0.76 and correct classification rate was 70 %. Regarding the UD group, during VFT, the highest value AUC [AUC = 0.822, 95%CI = 0.740-0.903] was recorded in the left dorsolateral prefrontal cortex with the optimal cut-off value (HbO2cutoff ≥0.163 µmol/ml for healthy controls; <0.163 for unipolar disorder), the sensitivity was 72 %; specificity was 82 %; PPV was 0.80; NPV was 0.75, correct classification rate was 77 %, and the Youden's index was 0.54. CONCLUSION: Assessing hemodynamics during VFT using portable fNIRS offers the potential as an adjunct diagnostic tool for mood disorders in low-resource environments.

Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder.

War and conflict are global phenomena, identified as stress-inducing triggers for epigenetic modifications. In this state-of-the-science narrative review based on systematic principles, we summarise existing data to explore the outcomes of these exposures especially in veterans and show that they may result in an increased likelihood of developing gastrointestinal, auditory, metabolic and circadian issues, as well as post-traumatic stress disorder (PTSD). We also note that, despite a potential "healthy soldier effect", both veterans and civilians with PTSD exhibit the altered DNA methylation status in hypothalamic-pituitary-adrenal (HPA) axis regulatory genes such as NR3C1. Genes associated with sleep (PAX8; LHX1) are seen to be differentially methylated in veterans. A limited number of studies also revealed hereditary effects of war exposure across groups: decreased cortisol levels and a heightened (sex-linked) mortality risk in offspring. Future large-scale studies further identifying the heritable risks of war, as well as any potential differences between military and civilian populations, would be valuable to inform future healthcare directives.

Co-application of ACC deaminase-producing rhizobial bacteria and melatonin improves salt tolerance in common bean (Phaseolus vulgaris L.) through ion homeostasis.

A comprehensive body of scientific evidence indicates that rhizobial bacteria and melatonin enhance salt tolerance of crop plants. The overall goal of this research was to evaluate the ability of Rhizobium leguminoserum bv phaseoli to suppress salinity stress impacts in common bean treated with melatonin. Treatments included bacterial inoculations (inoculated (RI) and non-inoculated (NI)), different salinity levels (non-saline (NS), 4 (S1) and 8 (S2) dS m-1 of NaCl) and priming (dry (PD), melatonin (PM100) and hydro (PH) priming) with six replications in growing media containing sterile sand and perlite (1:1). The results showed that the bacterial strain had the ability to produce indole acetic acid (IAA), ACC deaminase and siderophore. Plants exposed to salinity stress indicated a significant decline in growth, yield, yield components, nitrogen fixation and selective transport (ST), while showed a significant increase in sodium uptake. However, the combination of PM100 and RI treatments by improving growth, photosynthesis rate and nitrogen fixation positively influenced plant performance in saline conditions. The combined treatment declined the negative impacts of salinity by improving the potassium translocation, potassium to sodium ratio in the shoot and root and ST. In conclusion, the combination of melatonin and ACC deaminase producing rhizobium mitigated the negative effects of salinity. This result is attributed to the increased ST and decreased sodium uptake, which significantly reduced the accumulation of sodium ions in shoot.

Snapshot of health-related behaviours in adults living with disabilities 1 year into the COVID-19 pandemic: a cross-sectional survey study.

OBJECTIVES: This survey aimed to assess the status of a range of health-related behaviours 1 year after the coronavirus outbreak was declared a pandemic in adults living with disabilities comparative with those with no disabilities. DESIGN: This cross-sectional study reports findings from an online survey conducted in March 2021. Mann-Whitney U and Χ2 tests were used to compare a range of health behaviours including time spent self-isolating, smoking, alcohol consumption, exercise frequency and diet in adults with and without disabilities. SETTING: A convenience sample of UK adults was recruited through the researchers' personal and professional networks including UK-based sight loss sector charities, social media platforms and professional forums. PARTICIPANTS: A total of 123 UK participants completed the survey. OUTCOME MEASURES: COVID-19 diagnosis, time spent self-isolating, alcohol consumption frequency, exercise frequency, change in smoking habit and eating habits. RESULTS: No significant differences were found in alcohol consumption, smoking, water intake, breakfast, or fruit and vegetable intake. There were statistically significant differences in the time spent self-isolating (U=2061, p=0.001), exercise frequency (U=1171.5, p=0.005) and the amount of food eaten (χ2 (2)=9.60, p=0.008, Cramer's V=0.281). Although the majority in both groups reported exercising three to four times per week and eating what they should, those with disabilities were more likely to eat less than they should, not exercise at all and to have been self-isolating for over 6 months than participants with no disabilities. CONCLUSIONS: The data in this study present some key differences between the two groups, with those living with disabilities being more likely to report that they had been self-isolating for prolonged periods of time, not exercising at all, and not eating as much as they should . This raises concerns for the health and well-being of individuals with disabilities.

Integral effects of brassinosteroids and timber waste biochar enhances the drought tolerance capacity of wheat plant.

Drought stress is among the major threats that affect negatively crop productivity in arid and semi-arid regions. Probably, application of some additives such as biochar and/or brassinosteroids could mitigate this stress; however, the mechanism beyond the interaction of these two applications is not well inspected. Accordingly, a greenhouse experiment was conducted on wheat (a strategic crop) grown under deficit irrigation levels (factor A) i.e., 35% of the water holding capacity (WHC) versus 75% of WHC for 35 days while considering the following additives, i.e., (1) biochar [BC, factor B, 0, 2%] and (2) the foliar application of 24-epibrassinolide [BR, factor C, 0 (control treatment, C), 1 (BR1) or 3 (BR2) µmol)]. All treatments were replicated trice and the obtained results were statistically analyzed via the analyses of variance. Also, heat-map conceits between measured variables were calculated using the Python software. Key results indicate that drought stress led to significant reductions in all studied vegetative growth parameters (root and shoot biomasses) and photosynthetic pigments (chlorophyll a, b and total contents) while raised the levels of oxidative stress indicators. However, with the application of BC and/or BR, significance increases occurred in the growth attributes of wheat plants, its photosynthetic pigments, especially the combined additions. They also upraised the levels of enzymatic and non-enzymatic antioxidants while decreased stress indicators. Furthermore, they increased calcium (Ca), phosphorus (P) and potassium (K) content within plants. It can therefore be deduced that the integral application of BR and BC is essential to mitigate drought stress in plants.

Identifying neuroimaging biomarkers of major depressive disorder from cortical hemodynamic responses using machine learning approaches.

BACKGROUND: Early diagnosis of major depressive disorder (MDD) could enable timely interventions and effective management which subsequently improve clinical outcomes. However, quantitative and objective assessment tools for the suspected cases who present with depressive symptoms have not been fully established. METHODS: Based on a large-scale dataset (n = 363 subjects) collected with functional near-infrared spectroscopy (fNIRS) measurements during the verbal fluency task (VFT), this study proposed a data representation method for extracting spatiotemporal characteristics of NIRS signals, which emerged as candidate predictors in a two-phase machine learning framework to detect distinctive biomarkers for MDD. Supervised classifiers (e.g., support vector machine (SVM), k-nearest neighbors (KNN)) cooperated with cross-validation were implemented to evaluate the predictive capability of selected features in a training set. Another test set that was not involved in developing the algorithms enabled the independent assessment of the model's generalization. FINDINGS: For the classification with the optimal fusion features, the SVM classifier achieved the highest accuracy of 75.6% ± 4.7% in the nested cross-validation, and the correct prediction rate of 78.0% with a sensitivity of 75.0% and a specificity of 81.4% in the test set. Moreover, the multiway ANOVA test on clinical and demographic factors confirmed that twenty out of 39 optimal features were significantly correlated with the MDD-distinctive consequence. INTERPRETATION: The abnormal prefrontal activity of MDD may be quantified as diminished relative intensity and inappropriate activation timing of hemodynamic response, resulting in an objectively measurable biomarker for assessing cognitive deficits and screening MDD at the early stage. FUNDING: This study was funded by NUS iHeathtech Other Operating Expenses (R-722-000-004-731).

Primary Pulmonary Choriocarcinoma Treated With Neoadjuvant Chemotherapy and Lobectomy: A Case Report.

Primary pulmonary choriocarcinomas (PPC) are a rare form of extragonadal germ cell tumors (GCT). They present as lung nodules and secrete beta-human chorionic gonadotropin (ß-HCG). This is a rare case of PPC that presented insidiously in a postmenopausal woman. Clinical suspicion arose due to markedly elevated serum ß-HCG and lung tumor biopsy immunohistochemical staining negative for markers of small cell and non-small cell carcinomas of the lung. The diagnosis of PPC was made after staining positive for markers of GCTs including ß-HCG in the absence of a primary tumor in the reproductive organs. The patient was treated with neoadjuvant vincristine, ifosfamide, and cisplatin (VIP) chemotherapy, followed by video-assisted thoracoscopic surgery (VATS) with lobectomy and mediastinal lymph node dissection. This is the first reported case of PPC treated with VIP induction chemotherapy. The patient initially had complete pathologic response and remission; however, she presented with relapse at a nine-month follow-up with new pulmonary nodules and metastatic disease to the brain.

Cerebral Folate Metabolism in Post-Mortem Alzheimer's Disease Tissues: A Small Cohort Study.

We investigated the cerebral folate system in post-mortem brains and matched cerebrospinal fluid (CSF) samples from subjects with definite Alzheimer's disease (AD) (n = 21) and neuropathologically normal brains (n = 21) using immunohistochemistry, Western blot and dot blot. In AD the CSF showed a significant decrease in 10-formyl tetrahydrofolate dehydrogenase (FDH), a critical folate binding protein and enzyme in the CSF, as well as in the main folate transporter, folate receptor alpha (FRα) and folate. In tissue, we found a switch in the pathway of folate supply to the cerebral cortex in AD compared to neurologically normal brains. FRα switched from entry through FDH-positive astrocytes in normal, to entry through glial fibrillary acidic protein (GFAP)-positive astrocytes in the AD cortex. Moreover, this switch correlated with an apparent change in metabolic direction to hypermethylation of neurons in AD. Our data suggest that the reduction in FDH in CSF prohibits FRα-folate entry via FDH-positive astrocytes and promotes entry through the GFAP pathway directly to neurons for hypermethylation. This data may explain some of the cognitive decline not attributable to the loss of neurons alone and presents a target for potential treatment.