Measuring visual cortical oxygenation in diabetes using functional near-infrared spectroscopy

Aims: Diabetes mellitus affects about 6% of the world’s population, and the chronic complications of the disease may result in macro- and micro-vascular changes. The purpose of the current study was to shed light on visual cortical oxygenation in diabetic individuals. We then aimed to compare the haemodynamic response (HDR) to visual stimulation with glycaemic control, given the likelihood of diabetic individuals suffering from such macro- and micro-vascular insult. Methodology: Thirty participants took part in this explorative study, fifteen of whom had diabetes and fifteen of whom were non-diabetic controls. The HDR, measured as concentrations of oxyhaemoglobin [HbO] and deoxyhaemoglobin [HbR], to visual stimulation was recorded over the primary visual cortex (V1) using a dual-channel oximeter. The stimulus comprised a pattern-reversal checkerboard presented in a block design. Participants’ mean glycated haemoglobin (HbA1c) level (±SD) was 7.2±0.6% in the diabetic group and 5.5±0.4% in the non-diabetic group. Raw haemodynamic data were normalised to baseline, and the last 15 s of data from each ‘stimulus on’ and ‘stimulus off’ condition were averaged over seven duty cycles for each participant. Results: There were statistically significant differences in ∆[HbO] and ∆[HbR] to visual stimulation between diabetic and non-diabetic groups (p<0.05). In the diabetic group, individuals with type 1 diabetes displayed an increased [HbO] (p<0.01) and decreased [HbR] (p<0.05) compared to their type 2 counterparts. There was also a linear relationship between both ∆[HbO] and ∆[HbR] as a function of HbA1c level (p<0.0005). Conclusions: Our findings suggest that fNIRS can be used as a quantitative measure of cortical oxygenation in diabetes. Diabetic individuals have a larger HDR to visual stimulation compared to non-diabetic individuals. This increase in ∆[HbO] and decrease in ∆[HbR] appears to be correlated with HbA1c level

Measuring the foveal avascular zone in diabetes: a study using optical coherence tomography angiography

AIMS/INTRODUCTION: Diabetes is a global issue that currently affects 425 million people worldwide. One observable microvascular complication of this condition is a change in the foveal avascular zone (FAZ). In this study, we used optical coherence tomography angiography to investigate the effect of diabetes on the FAZ. MATERIALS AND METHODS: A total of 11 participants with diabetes and 11 participants without diabetes took part in this study. Participants in both groups were matched for age (P = 0.217) and sex (P = 0.338), and had no history of ocular disease. Macular optical coherence tomography angiography (OCT‐A) scans of participants’ right and left eyes were taken. Glycosylated hemoglobin (HbA(1c)) and blood glucose levels were also measured. The FAZ area was manually segmented at the levels of the superficial capillary plexus (FAZ(SCP)) and deep capillary plexus (FAZ(DCP)). RESULTS: There was a strong relationship between the FAZ area of participants’ right and left eyes (P ≤ 0.001) in both diabetes and non‐diabetes groups. In the diabetes group, the FAZ(SCP) (P = 0.047) and FAZ(DCP) (P = 0.011) areas was significantly larger than in the non‐diabetes group. Moreover, multiple linear regression analysis predicted a 0.07‐mm(2) increase in the FAZ(SCP) and FAZ(DCP) areas of individuals with diabetes for every 1% increase in their HbA(1c) level. CONCLUSIONS: Our findings show that there is enlargement of the FAZ in individuals with diabetes compared with individuals without diabetes. In the diabetes group, this enlargement appears to be correlated with HbA(1c) level. OCT‐A imaging could, therefore, be a useful tool to monitor the FAZ and identify potential early microvasculopathy in diabetes

The effect of stimulation technique on sympathetic skin responses in healthy subjects

The aim of this study was to collect normative data for sympathetic skin responses (SSR) elicited by electrical stimulus of the ipsilateral and contralateral peripheral nerves, and by magnetic stimulus of cervical cord. SSRs were measured at the mid-palm of both hands following electrical stimulation of the left median nerve at the wrist and magnetic stimulation at the neck in 40 healthy adult volunteers (mean age 52.2 ± 12.2 years, 19 males). The onset latency, peak latency, amplitude and area were estimated in “P” type responses (i.e., waveforms with a larger positive, compared to negative, component). SSR onset and peak latency were prolonged when the electrical stimulus was applied at the contralateral side (i.e., the SSR recorded in the right palm P < 0.001). The onset latency was similar on both sides during cervical magnetic stimulation. However, peak latency was faster on the left side (P < 0.03). Comparison of electrical and magnetic stimulation revealed that both the onset and peak latency were shorter with magnetic stimulation (P < 0.001). The latency of a SSR varies depending on what type of stimulation is used and where the stimulus is applied. Electrically generated SSRs have a longer delay and the delay is prolonged at the contralateral side. These factors should be taken into account when interpreting SSR data

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Background: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. Case presentation: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4(+) T cells and higher percentage of activated CD4(+) T cells at HAART initiation. The percentage of memory CD4(+) T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8(+) T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. Conclusion: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER). A FCT fellowship was attributed to RRS (PD/BD/106047/2015; Inter-University Doctoral Program in Ageing and Chronic Disease) and to CN [SFRH/BPD/65380/2009; Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE)]info:eu-repo/semantics/publishedVersio

The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine

Systemic therapy of Cushing’s syndrome

Cushing’s disease (CD) in a stricter sense derives from pathologic adrenocorticotropic hormone (ACTH) secretion usually triggered by micro- or macroadenoma of the pituitary gland. It is, thus, a form of secondary hypercortisolism. In contrast, Cushing’s syndrome (CS) describes the complexity of clinical consequences triggered by excessive cortisol blood levels over extended periods of time irrespective of their origin. CS is a rare disease according to the European orphan regulation affecting not more than 5/10,000 persons in Europe. CD most commonly affects adults aged 20–50 years with a marked female preponderance (1:5 ratio of male vs. female). Patient presentation and clinical symptoms substantially vary depending on duration and plasma levels of cortisol. In 80% of cases CS is ACTH-dependent and in 20% of cases it is ACTH-independent, respectively. Endogenous CS usually is a result of a pituitary tumor. Clinical manifestation of CS, apart from corticotropin-releasing hormone (CRH-), ACTH-, and cortisol-producing (malign and benign) tumors may also be by exogenous glucocorticoid intake. Diagnosis of hypercortisolism (irrespective of its origin) comprises the following: Complete blood count including serum electrolytes, blood sugar etc., urinary free cortisol (UFC) from 24 h-urine sampling and circadian profile of plasma cortisol, plasma ACTH, dehydroepiandrosterone, testosterone itself, and urine steroid profile, Low-Dose-Dexamethasone-Test, High-Dose-Dexamethasone-Test, after endocrine diagnostic tests: magnetic resonance imaging (MRI), ultra-sound, computer tomography (CT) and other localization diagnostics. First-line therapy is trans-sphenoidal surgery (TSS) of the pituitary adenoma (in case of ACTH-producing tumors). In patients not amenable for surgery radiotherapy remains an option. Pharmacological therapy applies when these two options are not amenable or refused. In cases when pharmacological therapy becomes necessary, Pasireotide should be used in first-line in CD. CS patients are at an overall 4-fold higher mortality rate than age- and gender-matched subjects in the general population. The following article describes the most prominent substances used for clinical management of CS and gives a systematic overview of safety profiles, pharmacokinetic (PK)-parameters, and regulatory framework

Tau-dependent suppression of adult neurogenesis in the stressed hippocampus

uncorrected proofStress, a well-known sculptor of brain plasticity, is shown to suppress hippocampal neurogenesis in the adult brain; yet, the underlying cellular mechanisms are poorly investigated. Previous studies have shown that chronic stress triggers hyperphosphorylation and accumulation of the cytoskeletal protein Tau, a process that may impair the cytoskeleton-regulating role (s) of this protein with impact on neuronal function. Here, we analyzed the role of Tau on stress-driven suppression of neurogenesis in the adult dentate gyrus (DG) using animals lacking Tau (Tau-knockout; Tau-KO) and wild-type (WT) littermates. Unlike WTs, Tau-KO animals exposed to chronic stress did not exhibit reduction in DG proliferating cells, neuroblasts and newborn neurons; however, newborn astrocytes were similarly decreased in both Tau-KO and WT mice. In addition, chronic stress reduced phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/glycogen synthase kinase-3 beta (GSK3 beta)/beta-catenin signaling, known to regulate cell survival and proliferation, in the DG of WT, but not Tau-KO, animals. These data establish Tau as a critical regulator of the cellular cascades underlying stress deficits on hippocampal neurogenesis in the adult brain.Portuguese Foundation for Science and Technology (FCT) Investigator grants (IF/01799/2013, IF/00883/2013, IF/01079/2014, respectively). This work was funded by FCT research grants 'PTDC/SAU-NMC/113934/2009' (IS), the Portuguese North Regional Operational Program (ON.2) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), the Project Estratégico co-funded by FCT (PEst-C/SAU/LA0026/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298) as well as the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)info:eu-repo/semantics/publishedVersio