Higher rates of false-positive HIV antigen/antibody screens during the COVID-19 pandemic: implications for pregnant patients

Objective: To compare the rates of false-positive HIV 4th generation screens among pregnant patients before and during the COVID-19 pandemic. Study Design: A retrospective study evaluating the rates of false-positive HIV 4th generation screens among 44,187 pregnant patients was conducted. Pregnant patients from 3/2017-3/2019 were assigned to the “pre-COVID” cohort, and pregnant patients from 3/2020-3/2022 were assigned to the “COVID” cohort. Data including the date(s) and results of HIV 4th generation Ag/Ab combination tests and SARS-CoV-2 RT-PCR assays were ascertained via chart review. An HIV 4th generation test result was deemed “false-positive” if subsequent HIV-1/HIV-2 antibody differentiation immunoassays and/or HIV-1 nucleic acid tests were non-reactive. Results: 42/22,073 (0.19%) patients with pre-COVID pregnancies who had HIV 4th generation tests were found to have abnormal results. In comparison, 71/22,114 (0.32%) patients with pregnancies during the pandemic had abnormal test results. 16/42 (38.1%) patients with abnormal results pre-COVID had false-positive HIV screens. In comparison, 48/71 (67.6%) COVID cohort patients with abnormal results had false-positive HIV screens. Overall, the rate of false-positive HIV 4th generation tests was significantly higher in the COVID cohort compared to the pre-COVID cohort (p=0.002). Among the 48 patients with false-positive HIV screens in the COVID cohort, 13 (27.1%) had a PCR-proven COVID-19 diagnosis during pregnancy preceding their false positive result. Interestingly, 9/13 patients (69.2%) also had at least one negative HIV 4th generation screening result predating their COVID-19 diagnosis. Conclusion: Considering the maternal and neonatal implications of a positive HIV test result, OB/GYNs should be cognizant that false-positive results can occur in the setting of new/prior COVID-19 infections. Shared decision making should be used when considering the initiation of combination antiretroviral therapy, route of delivery and/or delay of breastfeeding for patients with a newly positive HIV 4th generation tests, particularly in the absence of other risk factors

Positron emission tomography for staging of oesophageal and gastroesophageal malignancy.

Positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) was prospectively investigated as a means of detecting metastatic disease in patients with oesophageal tumours and compared with computerized tomography (CT), with the surgical findings as a gold standard. Twenty-six patients with a malignant tumour of the oesophagus or gastroesophageal junction underwent CT and PET of the chest and the abdomen. Seven patients underwent laparoscopy to establish resectability. Fifteen patients underwent laparotomy without prior laparoscopy. Four patients did not undergo surgery. The primary tumour was visualized in 81% of patients with CT and in 96% with PET. Neither CT nor PET were suited to assess the extent of wall invasion. Surgically assessed nodal status corresponded in 62% with CT and in 90% with PET. Distant metastases were found in five patients with CT and in eight with PET. The diagnostic accuracy of CT in determining resectability was 65% and for PET 88%. For CT and PET together this was 92%. The present study indicates that FDG-PET can be of importance for staging patients with oesophageal tumours. PET has a higher sensitivity for nodal and distant metastases and a higher accuracy for determining respectability than CT. PET and CT together would have decreased ill-advised surgery by 90%

Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J < C57BL/6J)-a non-contingent, drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes-heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1) and RUN and FYVE domain-containing 1 (Rufy1). Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2), a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J < C57BL/6J; p 4.2 x 10-15). Transcription activator-like effector nucleases (TALENs)-mediated introduction of frameshift deletions in the first coding exon of Hnrnph1, but not Rufy1, recapitulated the reduced methamphetamine behavioral response, thus identifying Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for prevention and treatment of substance abuse and possibly other psychiatric disorders

Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes

Parvalbumin-expressing (PV+) basket cells are fast-spiking inhibitory interneurons that exert critical control over local circuit activity and oscillations. PV+ axons are often myelinated, but the electrical and metabolic roles of interneuron myelination remain poorly understood. Here, we developed viral constructs allowing cell type-specific investigation of mitochondria with genetically encoded fluorescent probes. Single-cell reconstructions revealed that mitochondria selectively cluster to myelinated segments of PV+ basket cells, confirmed by analyses of a high-resolution electron microscopy dataset. In contrast to the increased mitochondrial densities in excitatory axons cuprizone-induced demyelination abolished mitochondrial clustering in PV+ axons. Furthermore, with genetic deletion of myelin basic protein the mitochondrial clustering was still observed at internodes wrapped by noncompacted myelin, indicating that compaction is dispensable. Finally, two-photon imaging of action potential-evoked calcium (Ca2+) responses showed that interneuron myelination attenuates both the cytosolic and mitochondrial Ca2+ transients. These findings suggest that oligodendrocyte ensheathment of PV+ axons assembles mitochondria to branch selectively fine-tune metabolic demands

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

OBJECTIVE: Loss of function of the astrocyte-specific protein MLC1 leads to the childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with subcortical cysts" (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. METHODS: We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole-cell patch-clamp recordings and K+-sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. RESULTS: An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+dynamics and neuronal network activity are abnormal in MLC mice. INTERPRETATION: Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636-649

Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3'-untranslated region of rat tyrosine hydroxylase mRNA

Reduced oxygen tension (hypoxia) induces a 3-fold increase in stability of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, in the pheochromocytoma (PC12) clonal cell line. To investigate the possibility that RNA-protein interactions are involved in mediating this increase in stability, RNA gel shift assays were performed using different fragments of labeled TH mRNA and the S-100 fraction of PC12 cytoplasmic protein extracts. We identified a sequence within the 3'-untranslated region of TH mRNA that binds cytoplasmic protein

A splicing factor that is inactivated during in vivo heat shock is functionally equivalent to the [U4/U6.U5] triple snRNP-specific proteins.

One of the consequences of the heat shock response in a shutdown of pre-mRNA splicing, a phenomenon that can be reproduced in extracts prepared from heat-shocked cells. The block in splicing occurs before the covalent modifications that generate spliced mRNA at the level of spliceosome formation. We have used extracts prepared from heat-shocked cells as a complementation system to characterize and partially purify a protein factor that is inactivated during the in vivo heat shock. The activity functions in the formation of the active spliceosome by assembling U4/U6 and U5 snRNPs into a triple snRNP particle.One of the consequences of the heat shock response in a shutdown of pre-mRNA splicing, a phenomenon that can be reproduced in extracts prepared from heat-shocked cells. The block in splicing occurs before the covalent modifications that generate spliced mRNA at the level of spliceosome formation. We have used extracts prepared from heat-shocked cells as a complementation system to characterize and partially purify a protein factor that is inactivated during the in vivo heat shock. The activity functions in the formation of the active spliceosome by assembling U4/U6 and U5 snRNPs into a triple snRNP particle

SEAFOODSENSE D18 Report on ETHICOD consumer study: detailed description of the procedures

The aim of this product test was to determine the effects of pre-slaughter stress on both the intrinsic sensory properties as well as the consumer perception of the products. Variables included the effect of information provided with the products, the effect of knowledge that the consumers have on welfare aspects, the effect of reliability of the information provided and the effect of the different test situations. The consumer tests were performed in both Iceland and The Netherlands both in an inEhome and a central location situation. Consumers’ attitude and behaviour towards animal welfare were asked. This report describes the procedures followed