Correlation of the Geriatric Assessment with Overall Survival in Older Patients with Cancer.

AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS: This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS: Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION: The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.

CT Perfusion Does Not Modify the Effect of Reperfusion in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment in the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing endovascular treatment, many patients still do poorly. We investigated whether CTP modifies the effect of near-complete reperfusion on clinical outcomes, ie, whether poor clinical outcomes despite near-complete reperfusion can be partly or fully explained by CTP findings. MATERIALS AND METHODS: Data are from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Admission CTP was processed using RAPID software, generating relative CBF and CBV volume maps at standard thresholds. CTP lesion volumes were compared in patients with-versus-without near-complete reperfusion. Associations between each CTP metric and clinical outcome (90-day mRS) were tested using multivariable logistic regression, adjusted for baseline imaging and clinical variables. Treatment-effect modification was assessed by introducing CTP lesion volume × reperfusion interaction terms in the models. RESULTS: CTP lesion volumes and reperfusion status were available in 410/1105 patients. CTP lesion volumes were overall larger in patients without near-complete reperfusion, albeit not always statistically significant. Increased CBF <34%, CBV <34%, CBV <38%, and CBV <42% lesion volumes were associated with worse clinical outcome (ordinal mRS) at 90 days. CTP core lesion volumes did not modify the treatment effect of near-complete recanalization on clinical outcome. CONCLUSIONS: CTP did not modify the effect of near-complete reperfusion on clinical outcomes. Thus, CTP cannot explain why some patients with near-complete reperfusion have poor clinical outcomes.

Patient-Relevant Deficits Dictate Endovascular Thrombectomy Decision-Making in Patients with Low NIHSS Scores with Medium-Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: There is a paucity of evidence regarding the safety of endovascular treatment for patients with acute ischemic stroke due to primary medium-vessel occlusion. The aim of this study was to examine the willingness among stroke physicians to perform endovascular treatment in patients with mild-yet-disabling deficits due to medium-vessel occlusion. MATERIALS AND METHODS: In an international cross-sectional survey consisting of 7 primary medium-vessel occlusion case scenarios, participants were asked whether the presence of personally disabling deficits would influence their decision-making for endovascular treatment despite the patients having low NIHSS scores (<6). Decision rates were calculated on the basis of physician characteristics. Univariable logistic regression clustered by respondent and scenario identity was performed. RESULTS: Three hundred sixty-six participants from 44 countries provided 2562 answers to the 7 medium-vessel occlusion scenarios included in this study. In scenarios in which the deficit was relevant to the patient's profession, 56.9% of respondents opted to perform immediate endovascular treatment compared with 41.0% when no information regarding the patient's profession was provided (risk ratio = 1.39, P < .001). The largest effect sizes were seen for female participants (risk ratio = 1.68; 95% CI, 1.35-2.09), participants older than 60 years of age (risk ratio = 1.61; 95% CI, 1.23-2.10), those with more experience in neurointervention (risk ratio = 1.60; 95% CI, 1.24-2.06), and those who personally performed >100 endovascular treatments per year (risk ratio = 1.63; 95% CI, 1.22-2.17). CONCLUSIONS: The presence of a patient-relevant deficit in low-NIHSS acute ischemic stroke due to medium-vessel occlusion is an important factor for endovascular treatment decision-making. This may have relevance for the conduct and interpretation of low-NIHSS endovascular treatment in randomized trials.

Vancomycin in adult prescribing: is it time to move on from trough-based dosing in the UK?

Vancomycin remains a useful agent in the infection doctor's toolkit, particularly for Staphylococcus aureus and MRSA infections. Therapeutic drug monitoring (TDM) is essential to maintain efficacy and avoid toxicity. Until recently, trough-based dosing has been the recommended method but in recent years the reliability of this has been questioned. The 2020 Infectious Diseases Society of America (IDSA) vancomycin guideline update has sent a clear message that trough-based dosing is not to be relied on, instead recommending dosing via 24 h AUC/MIC. The UK, however, has yet to follow suit in this, despite the wealth of evidence showing that trough-based dosing puts patients at higher risk of nephrotoxicity. Clearly, it is time to incorporate AUC/MIC-based dosing to utilize this effective antibiotic safely.

Particle composition and morphology over urban environment (New Delhi): Plausible effects on wheat leaves.

Particulate matter (PM) deposition on leaves adversely affects physical, chemical and biological nature of agricultural crops resulting in their loss of productivity and yield. Wheat being a staple food in major parts of Northern India and around the World, has been selected for research purpose by designing a study to explore the probable effects of PM deposition on wheat leaves and wheat crops to ensure the food security. PM5 (Particulate matter with aerodynamic diameter <5 µm) and Dry Deposited Particulate Matter (DDPM) on wheat leaves (Leaf_DDPM) were collected from the wheat crop field in Indian Agriculture Research Institute (IARI), New Delhi for growing and harvesting season of wheat crops (i.e. December 2014 to April 2015). The EDS (Energy Dispersive Spectroscopy) analysis was used for this study and the individual particle analysis revealed the presence of both acidic and alkaline components like C, Al, Si, Fe, Ca, K, S and Mg. The offline characterization tool i.e. SEM (Scanning Electron Microscope) was utilized for obtaining the micrographs which clearly showed the presence of some angular, sharp-edged and spherical particles consisting of both smooth and rough texture. Apart from that, prevalence of slightly non-spherical particles with aspect ratio of range (>1.20-1.40) and CIR (>0.70-0.80) for both PM5 and leaf_DDPM were observed. The size distribution of individual particles for both PM5(#194 particles) and Leaf_DDPM(#657 particles) revealed that Surface Equivalent Radius (SER) and Volume Equivalent Radius (VER) of particles observed to be 0.40-0.80 µm while surface area to be 0-1 µm2. These particles may easily block stomatal openings (with typical diameter range: 42-51 µm) of wheat leaves and damage internal leaf tissues while particle VER determines the interaction of incoming solar radiation with leaf surfaces. Average PM5 concentrations ± Standard deviations (µg/m3) were reported to be 231.05 ± 113.03. The XRF (X-Ray Fluorescence) spectrometer analysis of bulk PM5 revealed the concentrations of non-carbonaceous elements (µg/m3) as N (67.34 ± 16.09), Si (27.44 ± 11.01), Al (7.79 ± 3.37), S (3.88 ± 2.24), Na (2.29 ± 0.94), Mg (1.65 ± 0.62), K (0.51 ± 0.26), Ca (0.60 ± 0.26), Fe (0.54 ± 0.26), Cr (1.10 ± 0.70), Zn (0.05 ± 0.03), P (0.10 ± 0.03), Cu (0.07 ± 0.06). The dominant elemental oxides were calculated as SiO2, Al2O3, SO42-, Na2O, MgO, K2O, CaO, Fe2O3, Cr2O3, ZnO, P2O5, Cu2O with variable concentrations. In high humid conditions, with relative humidity (~85%) during the vegetative and flowering growth stages of wheat crops, presence of C and S rich acidic and hygroscopic particles may cause the corrosion of wheat leaves that ultimately affect the wheat crops.

Cardiac adaptation in asphyxiated infants treated with therapeutic hypothermia.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) affects  one to two newborns per 1,000 live births and oftentimes involves multi-organ insult. The objectives were to assess the evolution of cardiac function in infants with HIE treated with therapeutic hypothermia using echocardiography (ECHO). METHODS: Archived data during the period 2010-2016 was assessed. Amongst the infants with baseline ECHO assessments, a sub-cohort which had assessments in all the three phases (baseline/pre-active cooling [T1], cooling [T2] and rewarming [T3]) was analyzed separately. RESULTS: Thirty three infants formed part of the overall cohort, the gestation and birthweight were 39.6 ± 1.6 weeks and 3306 ± 583 g, respectively. Baseline (T1) information noted impaired cardiac performance (right ventricle stroke volume 1.08 ± 0.04 ml/kg, fractional area change [FAC] 24 ± 0.5% and tricuspid annular peak systolic excursion [TAPSE] 7.46 ± 0.11mm). Serial information was available for 24 of 33 infants. Cardiac function improved significantly between the cooling and the re-warming kphases. This included changes in right ventricular output (127 ± 34 vs 164 ± 47 ml/kg/min, p <0.01) and FAC (20 ± 3 vs 28 ± 2%, p<0.01). Pairwise comparisons for fractional shortening did not show significant changes. From the cooling to the rewarming phase, maximum change was noted in FAC (26.3 ± 9.8%) while minimum change was noted in fractional shortening (median, interquartile range) of 4.6% (1.4, 9.1). Significant correlation between TAPSE and time to peak velocity as a proportion of right ventricular ejection time was noted (r2 = 0.68, p <0.001). CONCLUSIONS: In infants with moderate to severe HIE, cardiac function evolves during various phases of therapeutic hypothermia. Low output state during cooling may be due to a combination of the disease state (HIE) and cooling therapy.

Experiences of Kidney Transplant Recipients as Patient Navigators.

BACKGROUND AND OBJECTIVE: The use of trained kidney transplant recipients as patient navigators resulted in increased completion of the steps in the transplant process by dialysis patients. We sought to understand the experiences of these patient navigators. SETTING AND PARTICIPANTS: Six kidney transplant recipients were hired and employed by transplant centers in Ohio, Kentucky, and Indiana. The transplant navigators received formal training as peer educators, met with dialysis patients on a regular basis, and provided tailored education and assistance about transplantation to each patient. They worked closely with the pretransplant coordinators and social workers to learn the details of each patient's transplant work-up. METHODOLOGY: We queried navigators using open-ended questions to learn about their experiences. Navigator responses were coded and common themes identified. A thematic auditor reviewed and refined the coding. RESULTS: Two primary categories of themes emerged about the navigator experience: 1. practical comments that supported programmatic or implementation observations of the navigators, and 2. affective comments that reflected a shared experience among the navigators and patients. The navigators were able to fill voids in the transplant process that were not fulfilled by other caregivers. This was accomplished by a natural bond based upon a shared experience (of dialysis and kidney failure) between the navigator and the patient. The patient and navigator became experiential partners. CONCLUSION: Kidney transplant recipients trained as patient navigators fill the role of a nontraditional medical provider, offer support during the transplant process, and provide an added benefit to complement routine dialysis and nephrology care.

Vascular aging and cardiac maladaptation in growth-restricted preterm infants.

OBJECTIVE: To assess arterial morphology and mechanics in preterm infants with fetal growth restriction (FGR) compared with those appropriate for gestational age (AGA) in the early neonatal period. STUDY DESIGN: This observational study involved 20 preterm FGR infants (28 to 32 weeks) of gestational age (GA) and birth weight (BW) <10th centile and 20 preterm AGA infants. Vascular ultrasound was performed to measure aortic properties. RESULTS: GA and BW of FGR and AGA infants were 29.8±1.3 vs 30±0.9 weeks (P=0.78) and 923.4±168 vs 1403±237 g (P<0.001), respectively. At 10.5±1.3 (s.d.) days after birth, blood pressure (systolic 51±3 vs 46±4 mm Hg, P<0.001) and maximum aorta intima-media thickness (621±76 vs 479±54 µm; P<0.001) were significantly higher in FGR infants. Arterial wall stiffness and peripheral resistance were also increased in the FGR infants (2.36±0.24 vs 2.14±0.24, P=0.008 and 22.2±5 vs 13.7±2.3 mm Hg min ml-1, P<0.001), respectively. Significant correlations between vascular mechanics and cardiac function were observed (resistance vs E/E', r=0.7 and Tei index, r=0.79). CONCLUSION: Maladaptive arterial-ventricular coupling was noted. Early detection may aid in early therapeutic strategies such as afterload reduction.

Bronchopulmonary dysplasia-associated pulmonary hypertension: clues from placental pathology.

OBJECTIVES: Bronchopulmonary dysplasia (BPD) and the associated complication of pulmonary hypertension (PH) leads to increased mortality and a longer length of stay among survivors. Placental histopathology may give early clues of subsequent events. The objective was to evaluate the relationship of maternal vascular underperfusion (MVU) changes on placental histopathology with subsequent development of BPD-associated PH in a cohort of extremely premature infants. STUDY DESIGN: In a cohort of preterm infants '⩽28 weeks' gestational age (GA) and with 'severe' BPD, this retrospective study evaluated specific placental histopathological changes and assessed the relationship with subsequent development of PH. 'Severe' BPD was defined as the need for ⩾30% oxygen and/or positive pressure ventilation at 36 weeks postmenstrual age. Placental and echocardiographic assessments were done by investigators masked to the grouping and clinical outcomes. RESULTS: Fifty six infants with severe BPD formed the cohort; PH was noted in 22 (39.3%) infants. The GA of the infants with and without PH was comparable (25.8±1.6 vs 25.8±1.3 weeks, P=0.9). On placental histopathological examination, 13 (23%) had features of MVU. On univariate logistic regression, the presence of changes consistent with MVU increased the relative risk of subsequent BPD-associated PH by 2.75 (95% confidence interval 1.56 to 4.85, P=0.004). The significance persisted after adjustment for GA. Stratification by the presence or absence of fetal growth restriction, yielded nonsignificant associations (P=0.17). CONCLUSION: Based on the results of the present study, specific placental histopathological changes may give early clues to the subsequent development of BPD-associated PH.

Clinician performed ultrasound in fetal growth restriction: fetal, neonatal and pediatric aspects.

Fetal growth restriction (FGR) affects 7-10% pregnancies. Conventional and tissue Doppler imaging has noted cardiac compromise during fetal and early neonatal periods in this cohort. In this article, we discuss the use of salient ultrasound parameters across age groups. During fetal life, certain feto-placental sonographic parameters have been linked to adverse perinatal outcomes and are predictive of later life hypertension. During the early postnatal period altered morphometry (hypertrophied and globular hearts) with sub-clinical impairment of cardiac function has been noted in both term and preterm infants with FGR. Vascular imaging has noted thickened and stiffer arteries in association with significantly elevated blood pressure. Similar findings in the pediatric age groups indicate persistence of these alterations, and have formed the basis of intervention studies. Assessment methodology and clinical relevance of these parameters, especially in designing and monitoring of intervention strategies is discussed. Frontline care givers (obstetricians and neonatologists) are increasingly using point of care ultrasound to discern these manifestations of FGR during the sub-clinical phase.

Does growth restriction increase the vulnerability to acute ventilation-induced brain injury in newborn lambs? Implications for future health and disease.

Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood-brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.

Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.

Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.

Human fetal growth restriction: a cardiovascular journey through to adolescence.

Intrauterine growth restriction has been noted to adversely impact morbidity and mortality in the neonatal period as well as cardiovascular well-being in adolescence and adulthood. Recent data based on a wide range of ultrasound parameters during fetal and neonatal life has noted early and persistent involvement of the cardiovascular system. Some of these measures are predictive of long-term morbidities. Assessment of vascular mechanics is a new and novel concept in this population, and opens up avenues for diagnosis, monitoring and evaluation of the likely effectiveness of interventions. Prevention of these adverse vascular and cardiac outcomes secondary to fetal growth restriction may be feasible and of clinical relevance. This review focuses on growth restriction in humans with respect to cardiovascular remodeling and dysfunction during fetal life, persistence of functional cardiac impairment during early childhood and adolescence, and possible preventive strategies.

A COMPARATIVE ANALYSIS OF METHYLATION STATUS OF TUMOR SUPPRESSOR GENES IN PAIRED BIOPSY AND SERUM SAMPLES FROM CERVICAL CANCER PATIENTS AMONG NORTH INDIAN POPULATION.

Tumor-specific genetic or epigenetic alterations have been detected in serum DNA in case of various types of cancers. In breast cancer, the detection of tumor suppressor gene hypermethylation has been reported in several body fluids. Promoter hypermethylation of some genes like MYOD1, CALCA, hTERT etc. has also been detected in serum samples from cervical cancer. The present study is the first report on the comparison of promoter hypermethylation of tumor suppressor genes likep14, p15, p16, p21, p27, p57, p53, p73, RARß2, FHIT, DAPK, STAT1 and-RB1 genes in paired biopsy and serum samples from cervical cancer patients among north Indian population. This is also the first report on the hypermethylation of these genes in serum samples from cervical cancer patients among north Indian population. According to the results of the present study, promoter hypermethylation of these genes can also be detected in serum samples of cervical cancer patients. The sensitivity of detection of promoter hypermethylation in serum samples of cervical cancer patients as compared to paired biopsy samples was found to be around 83.3%. It was observed that promoter hypermethylation was mainly observed in the serum samples in the higher stages and very rarely in the lower stages. The present study clearly showed that serum of patients with cervical cancer can also be used to study methylated genes as biomarkers.

Systemic arterial stiffness in infants with bronchopulmonary dysplasia: potential cause of systemic hypertension.

OBJECTIVE: Systemic hypertension is common among preterm infants with severe bronchopulmonary dysplasia (BPD); the exact cause is unknown. The objective of this preliminary hypothesis generating study was to examine systemic arterial structure and vasomotor function in a cohort of preterm infants with severe BPD, using a cohort of preterm infants without BPD and a cohort of term infants for comparison. STUDY DESIGN: After obtaining informed consent, we measured aortic wall thickness and vasomotor function by ultrasonography in 20 infants with severe BPD, 7 infants with no BPD, and compared them with 20 healthy term infants. RESULTS: Maximum aortic thickness was significantly higher in infants with BPD (827±163 µm) compared to those with no BPD (674±22 µm) and term infants (657±67 µm) (unadjusted P<0.0001). The input impedance was similarly elevated in the infants with BPD (574±127 dynes s( )cm(-5)) compared to those with no BPD (325±24 dynes s cm(-)(5)) or term infants (328±113 dynes s cm(-)(5)) (unadjusted P<0.0001). Stiffness index was significantly higher in the infants with BPD (3.4±0.6) compared to those with no BPD (2.6±0.3) or term infants (2.3±0.4) (unadjusted P<0.0001). Systemic vascular resistance was also significantly elevated in the infants with BPD. The results remained significant even after adjusting for gestational age and birth weight. Measures of vasomotor function significantly correlated with blood pressure. CONCLUSION: The aortic wall thickness and vasomotor function are significantly altered in preterm infants with severe BPD. These findings may explain the higher incidence of systemic hypertension in this population.

You eat what you are: autophagy inhibition as a therapeutic strategy in leukemia.

A deeper understanding of the role of autophagy, literally 'self-eating', in normal and cancer cell biology has emerged over the last few years. Autophagy serves as a vehicle for cells to respond to various stressors including genomic, hypoxic and nutrient stress, and to oppose mechanisms of 'programmed' cell death. Here, we review not only mechanisms of cell death and cell survival but also the early successes in applying autophagy inhibition strategies in solid tumors using the only currently available clinical inhibitor, oral hydroxychloroquine. In acute leukemia, currently available chemotherapy drugs promote cell death and demonstrate clinical benefit, but relapse and subsequent chemotherapy resistance is common. Increasing preclinical data suggest that autophagy is active in leukemia as a means of promoting cell survival in response to chemotherapy. We propose coupling autophagy inhibition strategies with current cytotoxic chemotherapy and discuss synergistic combinations of available anti-leukemic therapies with autophagy inhibition. Furthermore, novel autophagy inhibitors are in development and promise to provide new therapeutic opportunities for patients with leukemia.

A neuron-glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants.

Sleep is an essential process and yet mechanisms underlying it are not well understood. Loss of the Drosophila quiver/sleepless (qvr/sss) gene increases neuronal excitability and diminishes daily sleep, providing an excellent model for exploring the underpinnings of sleep regulation. Here, we used a proteomic approach to identify proteins altered in sss brains. We report that loss of sleepless post-transcriptionally elevates the CG7433 protein, a mitochondrial γ-aminobutyric acid transaminase (GABAT), and reduces GABA in fly brains. Loss of GABAT increases daily sleep and improves sleep consolidation, indicating that GABAT promotes wakefulness. Importantly, disruption of the GABAT gene completely suppresses the sleep phenotype of sss mutants, demonstrating that GABAT is required for loss of sleep in sss mutants. While SSS acts in distinct populations of neurons, GABAT acts in glia to reduce sleep in sss flies. Our results identify a novel mechanism of interaction between neurons and glia that is important for the regulation of sleep.