Prefrontal cortex astroglia modulate anhedonia-like behavior.

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.

Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior.

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.

A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding. RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery. CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.

Retrospective study of the incidence of sarcoidosis-like reaction in patients treated with immunotherapy.

AIM: To assess the frequency of radiographically evident drug-induced sarcoidosis-like reaction (DISR) in patients treated with anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy, anti-programmed cell death protein 1 (PD-1) therapy, or a combination of both in a single centre. MATERIALS AND METHODS: The images and medical records of 457 patients with metastatic melanoma or head and neck cancer treated with either anti-CTLA-4 therapy, anti-PD-1 therapy, or a combination of both at University of California medical centre were reviewed retrospectively and the incidence of radiological manifestations of DISR was assessed among these treatment groups. RESULTS: Radiological manifestations of DISR were found in 19/457 patients (4.1%). The mean interval from the initiation of immunotherapy to development of DISR was 5.5 months (range 2.3-13.5 months). Mean interval from radiological detection of DISR to imaging evidence of resolution was 5.8 months (range 1.6-18.3 months). Three patients out of 81 (3.7%), 11/297 (3.7%), and 5/79 (6.3%) developed sarcoidosis-like reaction after treatment with anti-CTLA-4 antibody, anti-PD-1 antibody, and a combination of both, respectively. Most patients with DISR were asymptomatic and did not require systemic therapy. Most patients did not demonstrate concomitant increased maximum standardised uptake value (SUVmax) in other organs on their integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). CONCLUSIONS: In the present retrospective study of patients treated with immune checkpoint inhibitors (ICIs), DISR occurred in approximately 3.7% of patients treated with either anti-CTLA-4 or anti-PD-1 antibody and 6.3% of patients treated with a combination of both.

Flow Diversion in the Treatment of Intracranial Aneurysms: A Pragmatic Randomized Care Trial.

BACKGROUND AND PURPOSE: Flow diversion is a recent endovascular treatment for intracranial aneurysms. We compared the safety and efficacy of flow diversion with the alternative standard management options. MATERIALS AND METHODS: A parallel group, prerandomized, controlled, open-label pragmatic trial was conducted in 3 Canadian centers. The trial included all patients considered for flow diversion. A Web-based platform 1:1 randomly allocated patients to flow diversion or 1 of 4 alternative standard management options (coiling with/without stent placement, parent vessel occlusion, surgical clipping, or observation) as prespecified by clinical judgment. Patients ineligible for alternative standard management options were treated with flow diversion in a registry. The primary safety outcome was death or dependency (mRS > 2) at 3 months. The composite primary efficacy outcome included the core lab-determined angiographic presence of a residual aneurysm, aneurysm rupture, progressive mass effect during follow-up, or death or dependency (mRS > 2) at 3-12 months. RESULTS: Between May 2011 and November 2020, three hundred twenty-three patients were recruited: Two hundred seventy-eight patients (86%) had treatment randomly allocated (139 to flow diversion and 139 to alternative standard management options), and 45 (14%) received flow diversion in the registry. Patients in the randomized trial frequently had unruptured (83%), large (52% ≥10 mm) carotid (64%) aneurysms. Death or dependency at 3 months occurred in 16/138 patients who underwent flow diversion and 12/137 patients receiving alternative standard management options (relative risk, 1.33; 95% CI, 0.65-2.69; P = .439). A poor primary efficacy outcome was found in 30.9% (43/139) with flow diversion and 45.6% (62/136) of patients receiving alternative standard management options, with an absolute risk difference of 14.7% (95% CI, 3.3%-26.0%; relative risk, 0.68; 95% CI, 0.50-0.92; P = .014). CONCLUSIONS: For patients with mostly unruptured, large, anterior circulation (carotid) aneurysms, flow diversion was more effective than the alternative standard management option in terms of angiographic outcome.

Imaging considerations for salvage surgery in nasopharyngeal carcinoma: what surgeons need to know.

Nasopharyngeal carcinoma is frequently an undifferentiated squamous cell carcinoma, which is primarily treated with radiotherapy with or without chemotherapy; however, for residual or recurrent cancer, salvage surgery is the treatment of choice for resectable disease because it reduces the significant morbidity associated with re-irradiation. This review highlights the current surgical approach, mapping the extent of disease with an emphasis on magnetic resonance imaging (MRI) and integrated positron-emission tomography (PET)/computed tomography (CT), imaging features that determine operability for nasopharyngectomy and neck dissection, and need for a succinct radiological report and multidisciplinary team discussion, which are of paramount importance for successful surgical planning.

Transcranial Doppler Velocities and Angiographic Vasospasm after SAH: A Diagnostic Accuracy Study.

BACKGROUND AND PURPOSE: After aneurysmal SAH, transcranial Doppler is commonly used to monitor cerebral vasospasm. The diagnostic accuracy of transcranial Doppler flow velocity values in detecting angiographic vasospasm in patients requiring urgent endovascular intervention has not been established. MATERIALS AND METHODS: We performed a retrospective analysis of a consecutive series of patients with aneurysmal SAH who underwent transcranial Doppler (index test) within 24 hours of conventional angiography (reference test). The judgment of 33%, 50%, and 66% degree of vessel narrowing on angiography was independently established by multiple neuroendovascular clinicians. Vessel-specific per-segment and per-patient transcranial Doppler velocities were studied using receiver operating characteristic curves, the Youden index, and minimal acceptable sensitivity models. Optimal mean flow-velocity thresholds were explored to calculate sensitivity and specificity using a per-patient judgment of vasospasm of at least 50% angiographic narrowing in any large arterial segment except A1. RESULTS: In 221 patients, vasospasm was found in 15%, 8%, and 4% of arteries when the degree of reference angiographic luminal narrowing was 33%, 50%, and 66%, respectively. Mean flow velocities were significantly higher in vasospastic segments (P = . 001), but per-segment exploratory analyses yielded unsound mean flow velocity thresholds. The Youden and minimal acceptable sensitivity models proposed mean flow velocity thresholds of approximately 160 cm/s for the anterior circulation and 80 cm/s for the posterior circulation in the per-patient diagnosis of angiographic vasospasm (≥50%), yielding a sensitivity of 80%-90% (95% CI, 0.77-0.96), but with a corresponding specificity of 50% (95% CI, 0.40-0.56). CONCLUSIONS: In this study, a threshold transcranial Doppler mean flow-velocity value that would accurately diagnose ≥50% angiographic vasospasm remained elusive.

Surface water quality status and prediction during movement control operation order under COVID-19 pandemic: Case studies in Malaysia.

Global concerns have been observed due to the outbreak and lockdown causal-based COVID-19, and hence, a global pandemic was announced by the World Health Organization (WHO) in January 2020. The Movement Control Order (MCO) in Malaysia acts to moderate the spread of COVID-19 through the enacted measures. Furthermore, massive industrial, agricultural activities and human encroachment were significantly reduced following the MCO guidelines. In this study, first, a reconnaissance survey was carried out on the effects of MCO on the health conditions of two urban rivers (i.e., Rivers of Klang and Penang) in Malaysia. Secondly, the effect of MCO lockdown on the water quality index (WQI) of a lake (Putrajaya Lake) in Malaysia is considered in this study. Finally, four machine learning algorithms have been investigated to predict WQI and the class in Putrajaya Lake. The main observations based on the analysis showed that noticeable enhancements of varying degrees in the WQI had occurred in the two investigated rivers. With regard to Putrajaya Lake, there is a significant increase in the WQI Class I, from 24% in February 2020 to 94% during the MCO month of March 2020. For WQI prediction, Multi-layer Perceptron (MLP) outperformed other models in predicting the changes in the index with a high level of accuracy. For sensitivity analysis results, it is shown that NH3-N and COD play vital rule and contributing significantly to predicting the class of WQI, followed by BOD, while the remaining three parameters (i.e. pH, DO, and TSS) exhibit a low level of importance.

Reliability of the Diagnosis of Cerebral Vasospasm Using Catheter Cerebral Angiography: A Systematic Review and Inter- and Intraobserver Study.

BACKGROUND AND PURPOSE: Conventional angiography is the benchmark examination to diagnose cerebral vasospasm, but there is limited evidence regarding its reliability. Our goals were the following: 1) to systematically review the literature on the reliability of the diagnosis of cerebral vasospasm using conventional angiography, and 2) to perform an agreement study among clinicians who perform endovascular treatment. MATERIALS AND METHODS: Articles reporting a classification system on the degree of cerebral vasospasm on conventional angiography were systematically searched, and agreement studies were identified. We assembled a portfolio of 221 cases of patients with subarachnoid hemorrhage and asked 17 raters with different backgrounds (radiology, neurosurgery, or neurology) and experience (junior ≤10 and senior >10 years) to independently evaluate cerebral vasospasm in 7 vessel segments using a 3-point scale and to evaluate, for each case, whether findings would justify endovascular treatment. Nine raters took part in the intraobserver reliability study. RESULTS: The systematic review showed a very heterogeneous literature, with 140 studies using 60 different nomenclatures and 21 different thresholds to define cerebral vasospasm, and 5 interobserver studies reporting a wide range of reliability (κ = 0.14-0.87). In our study, only senior raters reached substantial agreement (κ ≥ 0.6) on vasospasm of the supraclinoid ICA, M1, and basilar segments and only when assessments were dichotomized (presence or absence of ≥50% narrowing). Agreement on whether to proceed with endovascular management of vasospasm was only fair (κ ≤ 0.4). CONCLUSIONS: Research on cerebral vasospasm would benefit from standardization of definitions and thresholds. Dichotomized decisions by experienced readers are required for the reliable angiographic diagnosis of cerebral vasospasm.

Alcohol Consumption and Depression Among University Students and Their Perception of Alcohol Use.

OBJECTIVES: To investigate the association between alcohol use and depression among university students in Hong Kong, their stress-coping methods, and their knowledge and perception of the effects of alcohol on health. METHODS: 345 full-time undergraduate students from The University of Hong Kong were invited to complete a questionnaire to assess their alcohol consumption (Alcohol Use Disorders Identification Test, CAGE questionnaire), depressive symptoms (Patient Health Questionnaire-9), and stress-coping methods (Coping Orientation to Problems Experienced Inventory), as well as knowledge and perception of alcohol consumption on health. Multiple linear regression was used to determine significant variables associated with depressive symptoms. Multinominal logistic regression was used to determine the effect of such variables on depressive symptom caseness and AUDIT drinking risk groups. RESULTS: 43.2% of respondents were moderate- to high-risk drinkers, but only 23.2% were self-reported as moderate- to high-level drinkers. 57.9% of respondents had mild to severe depressive symptoms. Probable depression was more likely to occur in female students, those with higher general stress, those who do not use social support for stress-coping, and those who smoke. High-risk drinkers were more likely to occur in older students, smokers, those with higher household income, and those with higher general stress levels. Students with higher levels of depressive symptoms and higher risk of alcohol consumption were more likely to use avoidance for stress-coping. 89.5% of students considered alcohol consumption moderately to very harmful to health, but students demonstrated only moderate knowledge levels of alcohol consumption on health. CONCLUSION: Alcohol consumption and depressive symptoms are prevalent among university students in Hong Kong. The use of avoidance for stress-coping is common in those with higher levels of depressive symptoms and higher-risk drinkers. Students tend to avoid seeking help for depressive symptoms and potentially take up drinking as a coping strategy. Context-specific approaches should be used when providing counselling services for student wellbeing in university settings. Further education of university students on knowledge and perception of alcohol consumption on health should be provided.

A randomized trial of endovascular versus surgical management of ruptured intracranial aneurysms: Interim results from ISAT2.

BACKGROUND AND PURPOSE: Appropriate management of ruptured intracranial aneurysm (RIA) in patients eligible for surgical clipping but under-represented in or excluded from previous randomized trials remains undetermined. METHODS: The International Subarachnoid Aneurysm Trial-2 (ISAT-2) is a randomized care trial comparing surgical versus endovascular treatment (EVT) of RIA. All patients considered for surgical clipping but eligible for endovascular treatment can be included. The primary endpoint is death or dependency on modified Rankin score (mRS>2) at 1 year. Secondary endpoints are 1 year angiographic results and length of hospital stay. RESULTS: An interim analysis was performed after 103 patients were treated from November 2012 to July 2017 in 4 active centers. Fifty-two of the 55 patients allocated to surgery were treated by clipping, and 45 of the 48 allocated to EVT were treated by coiling, with 3 crossovers in each arm. The main endpoint (1 year mRS>2), available for 76 patients, was reached in 16/42 patients allocated to clipping (38%; 95%CI: 25%-53%), and 10/34 patients allocated to coiling (29%; 17%-46%). One year imaging results were available in 54 patients: complete aneurysm occlusion was found in 23/27 patients allocated to clipping (85%; 67%-94%), and 18/27 patients allocated to coiling (67%; 47%-81%). Hospital stay exceeding 20 days was more frequent in surgery (26/55 [47%; 34%-60%]) than EVT (9/48 [19%; 10%-31%]). CONCLUSION: Ruptured aneurysm patients for whom surgical clipping may still be best can be managed in a randomized care trial, which is feasible in some centers. More participating centers are needed.

Unusual case of hemangioblastoma of the cerebellopontine angle.

BACKGROUND: Hemangioblastomas are the most common primary tumor of the posterior fossa. There are few cases of hemangioblastoma of the cerebellopontine angle (CPA). When present in this location, hemangioblastoma presents a diagnostic challenge as its imaging findings closely resemble those of vestibular schwannoma (VS), which is much more common in the CPA. CASE DESCRIPTION: We report the case of a 42-year-old man presenting with vertigo and diplopia found to have a CPA tumor with imaging resembling VS. He underwent retrosigmoidal resection of his tumor, which was found to be a hemangioblastoma. CONCLUSION: Hemangioblastoma, though rare in the CPA, should be considered in the differential diagnosis of CPA tumors.

Knowledge, opinions and factors influencing practices regarding sugar in oral paediatric medications: a survey of Dunedin pharmacy staff.

BACKGROUND AND OBJECTIVES: Sugar, a known aetiological factor in dental decay, has been used in paediatric medications as a bulking agent, preservative and to improve taste. Although artificial sweeteners have largely replaced sugar, some prescribed and over-the-counter (OTC) paediatric medications and supplements containing sugar are still available in New Zealand. Little is currently known about the knowledge, opinions and practices of staff in NZ pharmacies regarding sugar-containing paediatric medications. This study was carried out to investigate these factors. METHODS: After ethical approval was obtained, questionnaires were delivered to all staff members at pharmacies in the greater Dunedin area. Quantitative statistical analysis was carried out using SPSS version 22.0 with the alpha value set at 0.05. Qualitative data were analysed using a general inductive technique. RESULTS: A total of 58 questionnaires were returned giving a pharmacy response rate of 63.0%. Some 29.9% of respondents thought the inclusion of sugar in medications necessary and 77.6% agreed that sugar in paediatric medications can contribute to dental decay. Most of the 67.2% who reported that they do not give advice to customers regarding sugar in medications and oral health, felt it was not a priority. Parental request was the main factor determining provision or recommendations regarding sugar-free options (87.9%). CONCLUSION: Although choice of a sugar-free medication can be limited by many factors, inter-professional collaboration and knowledge sharing on this topic would be advantageous. In addition, the provision of more formalised education, either as part of undergraduate pharmacy curricula or as part of continuing education, should be considered.

CD3bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+ T cells.

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. γδ T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3(bright) γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. CD3(bright) γδ T cells uniformly express the canonical germline encoded Vγ6/Vδ1(+) T-cell receptor. They are widely distributed with a preferential representation in the lungs and skin are negatively impacted in the absence of retinoic acid receptor-related orphan receptor gammat expression or endogenous flora. This population responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like receptor family, pyrin domain containing 3 (NLRP3)-inflammasome-dependent IL-1ß. Finally, we demonstrated that IL-17-producing CD3(bright) γδ T cells responded promptly and strongly to pneumococcal infection and during skin inflammation. Here, we propose a new way to specifically analyze IL-17-producing Vγ6/Vδ1(+) T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this γδ T-cell subset in respiratory and skin disorders.

The distribution of CY2PC19*2 allele in a Trinidadian population. Is Clopidogrel the right choice?

OBJECTIVE: To determine the distribution of the CYP2C19*2 allele among Trinidadians. DESIGN AND METHODS: This is a cross sectional study among 100 patients attending primary health centers within the North Central Region of Trinidad. A stratified sampling technique was used in which there were three mutually exclusive subgroups: those of South Asian descent (Indo-Trinidadians), African descent (Afro-Trinidadians) and mixed ethnicity. Subsequently, systematic sampling was applied to each stratum to improve the representativeness of the sample. Hence, the 100 subjects recruited for the study were 40 Indo-Trinidadians, 40 Afro-Trinidadians and 20 of mixed descent. Apart from baseline data which included age, gender and ethnicity, DNA was assessed for the CYP2C19*2 allelic variant using a PCR method. RESULTS: There was a high allelic frequency (37%) for CYP2C19*2 which was found to be more common among Indo-Trinidadians (47.5%, 95% CI 32.0-63.0) compared to Afro-Trinidadians (22.5%, 95% CI 9.6-35.4) or people of mixed origin (45%, 95% CI 23.2-66.8). There was a significant difference (p=0.019) between CYP2C19*2 frequencies for Indo-Trinidadians and Afro-Trinidadians. CONCLUSION: We provided evidence that the prevalence of CYP2C19*2 mutation was high in our setting.

Case Report: A Patient with Acute Cardiac Tamponade Secondary to Complicated Stanford Type A Intramural Haematoma - the role of CT.

Chest pain is a common presenting complaint in the emergency room of which acute aortic syndrome is a sinister cause associated with high morbidity. A contrastenhanced CT aortogram is often performed for initial evaluation at the first instance of suspicion. We present a patient with Stanford Type A intramural haematoma complicated by haemopericardium and acute cardiac tamponade and highlight the relevant CT signs that would alert the managing physician to urgent echocardiogram correlation and emergent cardiothoracic intervention.

Characterization and source identification of stormwater runoff in tropical urban catchments.

The characteristics of urban stormwater pollution in the tropics are still poorly understood. This issue is crucial to the tropical environment because its rainfall and runoff generation processes are so different from temperate regions. In this regard, a stormwater monitoring program was carried out at three urban catchments (e.g. residential, commercial and industrial) in the southern part of Peninsular Malaysia. A total of 51 storm events were collected at these three catchments. Samples were analyzed for total suspended solids, 5-day biochemical oxygen demand, chemical oxygen demand (COD), oil and grease, nitrate nitrogen, nitrite nitrogen, ammonia nitrogen (NH3-N), soluble reactive phosphorus and total phosphorus. Principal component analysis (PCA) and hierarchical cluster analysis were used to interpret the stormwater quality data for pattern recognition and identification of possible sources. The most likely sources of stormwater pollutants at the residential catchment were from surface soil and leachate of fertilizer from domestic lawns and gardens, whereas the most likely sources for the commercial catchment were from discharges of food waste and washing detergent. In the industrial catchment, the major sources of pollutants were discharges from workshops and factories. The PCA factors further revealed that COD and NH3-N were the major pollutants influencing the runoff quality in all three catchments.