Factors that Determine Catastrophic Expenditure for Tuberculosis Care: a Patient Survey in China

Background: Tuberculosis (TB) often causes catastrophic economic effects on both the individual suffering the disease and their households. A number of studies have analyzed patient and household expenditure on TB care, but there does not appear to be any that have assessed the incidence, intensity and determinants of catastrophic health expenditure (CHE) relating to TB care in China. That will be the objective of this paper. Methods: The data used for this study were derived from the baseline survey of the China Government – Gates Foundation TB Phase II program. Our analysis included 747 TB cases. Catastrophic health expenditure for TB care was estimated using two approaches, with households defined as experiencing CHE if their annual expenditure on TB care: (a) exceeded 10 % of total household income; and (b) exceeded 40 % of their non-food expenditure (capacity to pay). Chi-square tests were used to identify associated factors and logistic regression analysis to identify the determinants of CHE. Results: The incidence of CHE was 66.8 % using the household income measure and 54.7 % using non-food expenditure (capacity to pay). An inverse association was observed between CHE rates and household income level. Significant determinants of CHE were: age, household size, employment status, health insurance status, patient income as a percentage of total household income, hospitalization and status as a minimum living security household. Factors including gender, marital status and type of TB case had no significant associations with CHE. Conclusions: Catastrophic health expenditure incidence from TB care is high in China. An integrated policy expanding the free treatment package and ensuring universal coverage, especially the height of UHC for TB patients, is needed. Financial and social protection interventions are essential for identified at-risk groups

Glycoprotein Hormone Receptor Knockdown Leads to Reduced Reproductive Success in Male Aedes aegypti

Glycoprotein hormone receptors mediate a diverse range of physiological functions in vertebrate and invertebrate organisms. The heterodimeric glycoprotein hormone GPA2/GPB5 and its receptor LGR1, constitute a recently discovered invertebrate neuroendocrine signaling system that remains to be functionally characterized. We previously reported that LGR1 is expressed in the testes of adult Aedes aegypti mosquitoes, where its immunoreactivity is particularly regionalized. Here, we show that LGR1 immunoreactivity is associated with the centriole adjunct of spermatids and is observed transiently during spermatogenesis in mosquitoes, where it may act to mediate the regulation of flagellar development. RNA interference to downregulate LGR1 expression was accomplished by feeding mosquito larvae with bacteria that produced LGR1-specific dsRNA, which led to defects in spermatozoa, characterized with shortened flagella. LGR1 knockdown mosquitoes also retained ∼60% less spermatozoa in reproductive organs and demonstrated reduced fertility compared to controls. To date, the endocrine regulation of spermatogenesis in mosquitoes remains an understudied research area. The distribution of LGR1 and detrimental effects of its knockdown on spermatogenesis in A. aegypti indicates that this heterodimeric glycoprotein hormone signaling system contributes significantly to the regulation of male reproductive biology in this important disease-vector

Potassium Dependent Regulation of Astrocyte Water Permeability Is Mediated by cAMP Signaling

Astrocytes express potassium and water channels to support dynamic regulation of potassium homeostasis. Potassium kinetics can be modulated by aquaporin-4 (AQP4), the essential water channel for astrocyte water permeability regulation. We investigated whether extracellular potassium ([K+]o) can regulate astrocyte water permeability and the mechanisms of such an effect. Studies were performed on rat primary astrocytes and a rat astrocyte cell line transfected with AQP4. We found that 10mM [K+]o caused an immediate, more than 40%, increase in astrocyte water permeability which was sustained in 5min. The water channel AQP4 was a target for this regulation. Potassium induced a significant increase in intracellular cAMP as measured with a FRET based method and with enzyme immunoassay. We found that protein kinase A (PKA) could phosphorylate AQP4 in vitro. Further elevation of [K+]o to 35mM induced a global intracellular calcium response and a transient water permeability increase that was abolished in 5min. When inwardly rectifying potassium (Kir)-channels were blocked, 10mM [K+]o also induced a calcium increase and the water permeability increase no longer persisted. In conclusion, we find that elevation of extracellular potassium regulates AQP4 and astrocyte water permeability via intracellular signaling involving cAMP. A prolonged increase of astrocyte water permeability is Kir-channel dependent and this response can be impeded by intracellular calcium signaling. Our results support the concept of coupling between AQP4 and potassium handling in astrocytes

CSF Rhinorrhea After Endonasal Intervention to the Skull Base (CRANIAL) — Part 2:Impact of COVID-19

Background During the pandemic, there has been a concern about the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, particularly during endonasal neurosurgical operations. The Pituitary Society produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the impact of COVID-19. Methods A multicentre, prospective, observational cohort study was conducted at twelve tertiary neurosurgical units (UK and Ireland). Data were collected from March 23rd-July 31st, 2020 inclusive. Data points collected were patient demographics, pre-operative COVID-19 testing, intra-operative operative modifications, and 30-day COVID infection rates. Results 124 patients were included. 116 patients (n=116/124, 94%) underwent COVID-19 testing pre-operatively (TSA: 97/105, 92%; EEA: 19/19, 100%). One patient (n=1/115, 1%) tested positively for COVID-19 pre-operatively, requiring a delay of operation until the infection was confirmed as resolved. Asides from transient diabetes insipidus; no other complications were reported for this case. All theatre staff wore at least level 2 PPE. Adaptations to surgical techniques included minimising drilling, draping modifications, and using nasal iodine wash. At 30 days postoperatively, there was no evidence of COVID infection (symptoms or on formal testing) in our cohort, and no mortality. Conclusions Preoperative screening protocols and operative modifications have facilitated endonasal neurosurgery during the COVID-19 pandemic, with Pituitary Society guidelines followed for the majority of these operations. There was no evidence of COVID infection in our cohort, and no mortality, supporting the use of risk mitigation strategies to continue endonasal neurosurgery in subsequent pandemic waves

CSF Rhinorrhoea After Endonasal Intervention to the Skull Base (CRANIAL) - Part 1: Multicenter Pilot Study

Background: CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) is a prospective, multicentre observational study seeking to determine: (1) the scope of skull base repair methods used; and (2) corresponding rates of postoperative CSF rhinorrhoea in endonasal transsphenoidal (TSA) expanded endonasal approaches (EEA) for skull base tumours. We sought to pilot the project - assessing the feasibility and acceptability by gathering preliminary data. / Methods: A prospective, observational cohort pilot study was carried out at twelve tertiary UK neurosurgical units. Feedback regarding project positives and challenges were qualitatively analysed. / Results: 187 cases were included, 159 TSA (85%) and 28 EEA (15%). The most common pathologies included: pituitary adenomas (n=141/187), craniopharyngiomas (n=13/187) and skull-base meningiomas (n=4/187). The most common skull base repair techniques used were tissue glues (n=132/187, most commonly Tisseel®), grafts (n=94/187, most commonly fat autograft or Spongostan™) and vascularised flaps (n=51/187, most commonly nasoseptal). These repairs were most frequently supported by nasal packs (n=125/187) and lumbar drains (n=22/187). Biochemically-confirmed CSF rhinorrhoea occurred in 6/159 (3.8%) TSA and 2/28 (7.1%) EEA. Four TSA (3%) and two EEA (7%) cases required operative management for CSF rhinorrhoea (CSF diversion or direct repair). Qualitative feedback was largely positive (themes included: user-friendly and efficient data collection, strong support from senior team members) demonstrating acceptability. / Conclusions: Our pilot experience highlights the acceptability and feasibility of CRANIAL. There is a precedent for multicentre dissemination of this project, in order to establish a benchmark of contemporary skull base neurosurgery practice, particularly with respect to EEA cases

CSF Rhinorrhoea After Endonasal Intervention to the Skull Base (CRANIAL) - Part 1:Multicenter Pilot Study

Background CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) is a prospective, multicentre observational study seeking to determine: (1) the scope of skull base repair methods used; and (2) corresponding rates of postoperative CSF rhinorrhoea in endonasal transsphenoidal (TSA) expanded endonasal approaches (EEA) for skull base tumours. We sought to pilot the project - assessing the feasibility and acceptability by gathering preliminary data. Methods A prospective, observational cohort pilot study was carried out at twelve tertiary UK neurosurgical units. Feedback regarding project positives and challenges were qualitatively analysed. Results 187 cases were included, 159 TSA (85%) and 28 EEA (15%). The most common pathologies included: pituitary adenomas (n=141/187), craniopharyngiomas (n=13/187) and skull-base meningiomas (n=4/187). The most common skull base repair techniques used were tissue glues (n=132/187, most commonly Tisseel®), grafts (n=94/187, most commonly fat autograft or Spongostan™) and vascularised flaps (n=51/187, most commonly nasoseptal). These repairs were most frequently supported by nasal packs (n=125/187) and lumbar drains (n=22/187). Biochemically-confirmed CSF rhinorrhoea occurred in 6/159 (3.8%) TSA and 2/28 (7.1%) EEA. Four TSA (3%) and two EEA (7%) cases required operative management for CSF rhinorrhoea (CSF diversion or direct repair). Qualitative feedback was largely positive (themes included: user-friendly and efficient data collection, strong support from senior team members) demonstrating acceptability. Conclusions Our pilot experience highlights the acceptability and feasibility of CRANIAL. There is a precedent for multicentre dissemination of this project, in order to establish a benchmark of contemporary skull base neurosurgery practice, particularly with respect to EEA cases. Keywords Cerebrospinal fluid rhinorrhoeaCSFCerebrospinal fluid leakskull base surgeryendoscopic endonasalEE

The Increased Activity of TRPV4 Channel in the Astrocytes of the Adult Rat Hippocampus after Cerebral Hypoxia/Ischemia

The polymodal transient receptor potential vanilloid 4 (TRPV4) channel, a member of the TRP channel family, is a calcium-permeable cationic channel that is gated by various stimuli such as cell swelling, low pH and high temperature. Therefore, TRPV4-mediated calcium entry may be involved in neuronal and glia pathophysiology associated with various disorders of the central nervous system, such as ischemia. The TRPV4 channel has been recently found in adult rat cortical and hippocampal astrocytes; however, its role in astrocyte pathophysiology is still not defined. In the present study, we examined the impact of cerebral hypoxia/ischemia (H/I) on the functional expression of astrocytic TRPV4 channels in the adult rat hippocampal CA1 region employing immunohistochemical analyses, the patch-clamp technique and microfluorimetric intracellular calcium imaging on astrocytes in slices as well as on those isolated from sham-operated or ischemic hippocampi. Hypoxia/ischemia was induced by a bilateral 15-minute occlusion of the common carotids combined with hypoxic conditions. Our immunohistochemical analyses revealed that 7 days after H/I, the expression of TRPV4 is markedly enhanced in hippocampal astrocytes of the CA1 region and that the increasing TRPV4 expression coincides with the development of astrogliosis. Additionally, adult hippocampal astrocytes in slices or cultured hippocampal astrocytes respond to the TRPV4 activator 4-alpha-phorbol-12,-13-didecanoate (4αPDD) by an increase in intracellular calcium and the activation of a cationic current, both of which are abolished by the removal of extracellular calcium or exposure to TRP antagonists, such as Ruthenium Red or RN1734. Following hypoxic/ischemic injury, the responses of astrocytes to 4αPDD are significantly augmented. Collectively, we show that TRPV4 channels are involved in ischemia-induced calcium entry in reactive astrocytes and thus, might participate in the pathogenic mechanisms of astroglial reactivity following ischemic insult

ICAR: endoscopic skull‐base surgery

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