Outcomes of combined endoscopic vitrectomy and posteriorly placed glaucoma drainage devices in pediatric patients.

BACKGROUND: This study aims to describe outcomes of posteriorly-placed glaucoma drainage devices (GDD) with concurrent endoscopic vitrectomy in pediatric patients with glaucoma and corneal opacification. METHODS: This retrospective case series identified patients under 18 years of age who underwent posteriorly-placed GDD implantation with concurrent endoscopic vitrectomy between 2012 and 2021. Data collected included ocular diagnoses, prior intraocular surgeries, type and position of GDD, surgical complications, and additional surgeries. Preoperative and final visual acuity, intraocular pressure (IOP), number of glaucoma medications, and exam findings were also recorded. Surgical data included type and position of GDD, Success was defined as IOP between 5-21 mmHg without visually devastating complication or need for additional glaucoma surgery. RESULTS: Ten patients (14 eyes) with sclerocornea (6), Peters Anomaly (4), corneal decompensation from increased IOP (3), and corneal scar (1) underwent combined endoscopic vitrectomy with posteriorly-placed GDD (Baerveldt (10 eyes), Ahmed (4 eyes)) at 4.6 ± 5.8 years of age. Four eyes of 3 patients remained successful at final follow-up, while 10 eyes of 7 patients required 2.4 ± 1.3 additional surgeries for glaucoma (7) or hypotony (3). Kaplan Meier analysis demonstrated 1- and 2-year survival rates of 36% and 18%, respectively. At final follow-up (3.7 ± 2.4 years), after an average of 4.4 ± 2.4 glaucoma surgeries, 13 of 14 eyes had obtained IOP control on significantly fewer (p<0.0001) IOP-lowering medications. Additional complications included retinal detachment (2), chronic corneal graft failure (2), phthisis (1) and band keratopathy (1). CONCLUSIONS: Management of glaucoma in pediatric eyes with corneal opacification is challenging and often requires multiple surgeries. A combined endoscopic vitrectomy and posteriorly placed GDD is a viable technique to establish aqueous humor outflow. Although the success rate is low, this surgical approach may be useful in ultimately obtaining IOP control and preserving vision in these complex eyes.

Long-term safety and efficacy of a fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis: phase 3 open-label study.

BACKGROUND: The topical corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (TAZ) are effective in psoriasis treatment. To mitigate adverse cutaneous reactions observed with monotherapy, a fixed- combination HP 0.01%/TAZ 0.045% lotion has been developed for the treatment of plaque psoriasis in adults. OBJECTIVES: To investigate the long-term safety, efficacy and maintenance of response with HP/TAZ lotion. METHODS: This was a 1-year, multicentre, open-label study in 555 adults with psoriasis [Investigator's Global Assessment (IGA) score of 3 ('moderate') or 4 ('severe') and body surface area (BSA) of 3-12% at baseline]. HP/TAZ was administered once daily for 8 weeks and then intermittently as needed in 4-week intervals for up to 1 year based on achievement of treatment success [IGA score of 0 ('clear') or 1 ('almost clear')]. Maximum continuous exposure was 24 weeks. RESULTS: Of 550 participants with postbaseline safety data, 318 (57.8%) achieved treatment success during the study. Of those, 54.4% achieved treatment success within the first 8 weeks; retreatment was not required for >4 weeks in over half (55.3%), and 6.6% did not require any retreatment. Among participants enrolled for the full 52 weeks, 77.5% maintained BSA ≤5% on treatment. There were marked improvements in severity of itching, dryness and burning/stinging over the study course. The most common treatment-related adverse events were application site reactions of dermatitis, pruritus, pain and irritation. CONCLUSIONS: Fixed-combination HP/TAZ lotion provided maintained efficacy with a favourable tolerability and safety profile, supporting its use for the long-term treatment and management of moderate-to-severe plaque psoriasis.

Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1).

BACKGROUND: Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks. OBJECTIVES: To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment. METHODS: At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re-treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure-adjusted rates of treatment-emergent adverse events. RESULTS: Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed. CONCLUSIONS: These findings indicate that brodalumab is efficacious and safe for continuous long-term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.

Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials.

BACKGROUND: Obesity is associated with psoriasis and negatively affects response to therapy. OBJECTIVES: To evaluate the efficacy and safety of brodalumab in nonobese vs. obese patients with psoriasis. METHODS: This is a post hoc analysis of the prospective, phase III, multicentre, randomized, placebo- and active-comparator-controlled AMAGINE-2 and AMAGINE-3 trials, in which patients were randomized to treatment with brodalumab 210 mg every 2 weeks, ustekinumab or placebo for a 12-week induction phase. At week 12, patients who received brodalumab 210 mg every 2 weeks continued brodalumab, those treated with ustekinumab continued ustekinumab, and those who received placebo switched to brodalumab 210 mg every 2 weeks. Patients were categorized by body mass index (BMI) category (< 30 or ≥ 30 kg m-2 ) and efficacy was evaluated using the physician-rated Psoriasis Area and Severity Index and static Physician's Global Assessment instruments. RESULTS: In total, 281 of 687 patients (40·9%) were obese. Skin clearance was comparable across BMI subgroups in brodalumab-treated patients. Psoriasis Area and Severity Index 100% improvement rates in nonobese and obese patients at week 12 were 54·1% and 49·5%, respectively, and at week 52 they were 72·6% and 64·8%, respectively. Week 12 ustekinumab responses were lower than brodalumab responses and were 6-17% lower in obese than in nonobese patients. No appreciable differences in overall safety were observed between nonobese and obese patients. CONCLUSIONS: The efficacy and safety of brodalumab did not differ between patients with moderate-to-severe psoriasis who had a BMI < 30 kg m-2 or a BMI ≥ 30 kg m-2 .

Number of friends and self-perception among Jamaican children: the role of attractiveness and fluctuating asymmetry.

The role that physical attractiveness and fluctuating asymmetry (FA), a measure of developmental instability, play in self-perception and peer associations were explored in a well-studied cohort of Jamaican children using a novel research paradigm where subjects were already known to each other for extensive periods of time. The results showed that how attractive a child was perceived by others was significantly positively correlated with self-ratings of attractiveness. Contrary to findings from WEIRD (Western, Educated, Industrialized, Rich, Democratic) samples, the study found a reversal in the sex differences in self-perceived attractiveness and self-esteem, where Jamaican females rate themselves more attractive and report higher self-esteem than do males. Attractiveness also predicts overall popularity, as measured by desirability as a friend and the percentage of peers who choose an individual as a friend. Attractive individuals of both sexes were chosen more often as 'friends'. A significant correlation was also found between an individual's FA and the average FA of those chosen as friends. However, the effect was primarily due to preferences by males for female friends possessing similar levels of FA, which could be an effective strategy in reducing future mating effort.

Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

AIMS: To study the impact of glycaemic control on urinary incontinence in women who participated in the Diabetes Control and Complications Trial (DCCT; 1983-1993) and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC; 1994-present). METHODS: Study participants were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC follow-up, the urological assessment questionnaire (UroEDIC). Urinary incontinence was defined as self-reported involuntary leakage of urine that occurred at least weekly. Incident urinary incontinence was defined as weekly urinary incontinence present at EDIC year 17 but not at EDIC year 10. Multivariable regression models were used to examine the association of incident urinary incontinence with comorbid prevalent conditions and glycaemic control (mean HbA1c over the first 10 years of EDIC). RESULTS: A total of 64 (15.3%) women with Type 1 diabetes (mean age 43.6 ± 6.3 years at EDIC year 10) reported incident urinary incontinence at EDIC year 17. When adjusted for clinical covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), the mean EDIC HbA1c was associated with increased odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01-1.06 per mmol/mol increase; odds ratio 1.41, 95% CI 1.07-1.89 per % HbA1c increase). CONCLUSIONS: Incident urinary incontinence was associated with higher HbA1c levels in women with Type 1 diabetes, independent of other recognized risk factors. These results suggest the potential for women to modify their risk of urinary incontinence with improved glycaemic control. (Clinical Trials Registry no: NCT00360815 and NCT00360893).

Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy.

PURPOSE: The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. METHODS: A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. RESULTS: Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. CONCLUSIONS: The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

Development of a new lingual range-of-motion assessment scale: normative data in surgically treated oral cancer patients.

Surgical resection in oral cancer patients can result in altered speech, swallowing, and patient perception of quality of life (QOL). Oral surgery can result in reduced lingual range of motion (ROM). However, few studies have quantified the degree of lingual restriction after surgery. This pilot study describes a new measurement system to define tongue ROM in surgically treated tongue cancer patients. This measurement system was validated by comparing results in these treated surgical patients versus healthy individuals. This scale was further validated by correlating ROM with performance status, oral outcomes, and patient-rated QOL. Thirty-six patients who underwent oral tongue surgery and 31 healthy individuals were included. Tongue ROM was assessed using a novel ROM assessment system. This novel system was examined in these patients versus healthy subjects. This measurement tool was further validated by correlating tongue ROM in treated patients with performance status, oral outcomes, and patient-rated QOL. Tongue ROM was found to be significantly lower in the surgically treated patients than in the healthy individuals (p = 0.0001). Tongue ROM correlated with performance status, oral outcomes, and all QOL measures. This new tongue ROM measurement system defined tongue deficits in surgically treated oral cancer patients. This tool was validated by comparing results to those in healthy individuals, as well as by correlating tongue ROM to performance status, oral outcomes, and QOL. This measurement tool can be used to define baseline and postsurgery tongue ROM in oral cancer patients, as well as track change over time with recovery and therapy. Future studies should examine use of this measurement tool with other populations demonstrating tongue deficits.

Functional outcomes and quality of life after chemoradiotherapy: baseline and 3 and 6 months post-treatment.

Concomitant chemoradiotherapy provides organ preservation for those patients with head and neck cancer. We report the results of a prospective study that examined functional outcomes and quality of life (QOL) after chemoradiotherapy over the first 6 months post-treatment (tx). Twenty-nine patients with head and neck cancer were treated with chemoradiotherapy. All were seen baseline and 3 and 6 months post-tx. Assessments included the performance status scale (PSS), Karnofsky performance status scale, tongue strength, jaw opening, and saliva weight. QOL was patient-rated using the eating assessment tool (EAT-10), MD Anderson dysphagia inventory, speech handicap index (SHI), and the EORTC H&N35 scale. Repeated-measures ANOVAs were used, with significance at p < 0.05. PSS scores were significantly different across time points. Tongue strength, jaw range of motion (ROM), and saliva weight were significantly lower at 3 and 6 months than at baseline. QOL was significantly worse after tx, although it improved by 6 months as rated with the EAT-10 and the SHI scores were significantly worse at 3 and 6 months. EORTC domains of swallowing, senses, speech, dry mouth, and sticky saliva were significantly worse at 3 and 6 months. Concomitant chemoradiotherapy for treatment of head and neck tumors can result in impaired performance outcomes and QOL over the first 6 months post-tx. However, performance status, tongue strength, jaw ROM, and eating QOL were only mildly impaired by 6 months post-tx. Saliva production and speech QOL remained significantly impaired at 6 months post-treatment. Current studies are examining outcomes at 12 and 24 months post-treatment to better predict outcomes over time in this population.

Conserving large populations of lions - the argument for fences has holes.

Packer et al. reported that fenced lion populations attain densities closer to carrying capacity than unfenced populations. However, fenced populations are often maintained above carrying capacity, and most are small. Many more lions are conserved per dollar invested in unfenced ecosystems, which avoid the ecological and economic costs of fencing.

Genome size and ploidy of Thysanoptera.

Flow cytometry was used to study the genome sizes and ploidy levels for four thrips species: Franklinothrips orizabensis Johansen (Thysanoptera: Aeolothripidae), Frankliniella occidentalis Pergande, Frankliniella fusca Hinds, and Thrips tabaci Lindeman (Thysanoptera: Thripidae). F. orizabensis males and females had 1C genome sizes of 426 Mb and 422 Mb, respectively. Male and female F. fusca had 1C genome sizes of 392 Mb and 409 Mb, whereas F. occidentalis males and females had smaller 1C genomes that were 345 Mb and 337 Mb, respectively. Male F. orizabensis, F. occidentalis and F. fusca were haploid and females diploid. Five isofemale lines of T. tabaci, initiated from parthenogenetic, thelytokous females and collected from different locations in North Carolina, were included in this study; no males were available. One isofemale line was diploid with a genome size of 1C = 310 Mb, and the other four had a mean genome size of 1C = 482 Mb, which is consistent with evidence from microsatellite data of diploidy and polyploidy, respectively, in these same five thelytokous lines. This is the first study to produce genome size estimates for thysanopteran species, and report polyploidy in T. tabaci populations.

Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort.

AIMS/HYPOTHESIS: In patients with type 1 diabetes, there has been concern about the effects of recurrent hypoglycaemia and chronic hyperglycaemia on cognitive function. Because other biomedical factors may also increase the risk of cognitive decline, this study examined whether macrovascular risk factors (hypertension, smoking, hypercholesterolaemia, obesity), sub-clinical macrovascular disease (carotid intima-media thickening, coronary calcification) and microvascular complications (retinopathy, nephropathy) were associated with decrements in cognitive function over an extended time period. METHODS: Type 1 diabetes patients (n = 1,144) who had completed a comprehensive cognitive test battery at entry into the Diabetes Control and Complications Trial were re-assessed at a mean of 18.5 (range: 15-23) years later. Univariate and multivariable models examined the relationship between cognitive change and the presence of micro- and macrovascular complications and risk factors. RESULTS: Univariate modelling showed that smoking history was modestly associated with decrements in learning, memory, spatial information-processing and psychomotor efficiency; hypertension was associated with only psychomotor slowing. Multivariable modelling demonstrated that HbA(1c) level, and retinal and renal complications were each independently associated with decrements in psychomotor efficiency. In contrast, no macrovascular risk factors were significant after correcting for multiple comparisons. No interactions were found between these predictors and sex, severe hypoglycaemic events or presence of the APOE ε4 allele. CONCLUSIONS/INTERPRETATION: In relatively healthy, middle-aged adults with type 1 diabetes who had been followed for an average of 18.5 years, long-term metabolic control and microvascular factors are independently associated with a decline in cognitive function specifically affecting measures of psychomotor efficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360893.

mRNA stability: in trans-it.

The regulation of mRNA stability is an important step in the control of gene expression. Characterization of the mechanisms involved in the turnover of individual mRNAs has identified a requirement for specific cis-acting sequences and trans-acting factors, as well as an involvement of the translation apparatus. In the past year, significant progress has been made in the identification of trans-acting factors by both biochemical and genetic approaches. This review summarizes that progress and promotes the notion that the ribosome itself should also be considered as a trans-acting component of the mRNA decay machinery.

The associations of apolipoprotein E and angiotensin-converting enzyme polymorphisms and cognitive function in Type 1 diabetes based on an 18-year follow-up of the DCCT cohort.

AIMS: Specific polymorphisms of the apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) genes appear to increase risk for Alzheimer's disease and cognitive dysfunction in the general population, yet little research has examined whether genetic factors influence risk of cognitive dysfunction in patients with Type 1 diabetes. The long-term follow-up of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) population provides an opportunity to examine if specific genetic variations in APOE and ACE alter risk for cognitive decline. METHODS: Neurocognitive function in Type 1 diabetic subjects from the DCCT/EDIC study was assessed at DCCT entry and re-assessed approximately 18 years later, using a comprehensive cognitive test battery. Glycated haemoglobin (HbA(1c)) and the frequency of severe hypoglycaemic events leading to coma or seizures were measured over the 18-year follow-up. We determined whether the APO epsilon4 and ACE intron 16 indel genotypes were associated with baseline cognitive function and with change over time, and whether they conferred added risk in those subjects experiencing severe hypoglycaemic events or greater glycaemic exposure. RESULTS: None of the APOE or ACE polymorphisms were associated with either baseline cognitive performance or change in cognition over the 18-year follow-up. Moreover, none of the genotype variations altered the risk of cognitive dysfunction in those subjects with severe hypoglycaemic episodes or high HbA(1c). CONCLUSIONS: In this sample of young and middle-aged adults with Type 1 diabetes, APO epsilon4 and ACE D alleles do not appear to increase risk of cognitive dysfunction.

Characterization of particulate matter size distributions and indoor concentrations from kerosene and diesel lamps.

UNLABELLED: Over one-quarter of the world's population relies on fuel-based lighting. Kerosene lamps are often located in close proximity to users, potentially increasing the risk for respiratory illnesses and lung cancer. Particulate matter concentrations resulting from cook stoves have been extensively studied in the literature. However, characterization of particulate concentrations from fuel-based lighting has received minimal attention. This research demonstrates that vendors who use a single simple wick lamp in high-air-exchange market kiosks will likely be exposed to PM(2.5) concentrations that are an order of magnitude greater than ambient health guidelines. Using a hurricane lamp will reduce exposure to PM(2.5) and PM(10) concentrations by an order of magnitude compared to using a simple wick lamp. Vendors using a single hurricane or pressure lamp may not exceed health standards or guidelines for PM(2.5) and PM(10), but will be exposed to elevated 0.02-0.3 µm particle concentrations. Vendors who change from fuel-based lighting to electric lighting technology for enhanced illumination will likely gain the ancillary health benefit of reduced particulate matter exposure. Vendors exposed only to ambient and fuel-based lighting particulate matter would see over an 80% reduction in inhaled PM(2.5) mass if they switched from a simple wick lamp to an electric lighting technology. PRACTICAL IMPLICATIONS: Changing lighting technologies to achieve increased efficiency and energy service levels can provide ancillary health benefits. The cheapest, crudest kerosene lamps emit the largest amounts of PM(2.5). Improving affordability and access to better lighting options (hurricane or pressure lamps and lighting using grid or off-grid electricity) can deliver health benefits for a large fraction of the world's population, while reducing the economic and environmental burden of the current fuel-based lighting technologies.

Radiographic digit ratios (2D:4D) of Afro-Caribbean children: Comparisons with published data from white children.

BACKGROUND: Digit ratio (2D:4D) from soft-tissue measurements of fingers from children and adults from Black and White ethnic groups show sex differences (males

Irreversible ligands with high selectivity toward delta and mu opiate receptors.

Alkylating agents that display strong selectivity for opiate receptor types delta or mu were prepared by appropriate modification of the structures of the strong analgesics fentanyl, etonitazene, and endoethenotetrahydrooripavine. The availability of these substances should facilitate studies of the structural basis of receptor specificity and of the physiologic roles of these receptors.

Resistance to pyrethroid insecticides in Helicoverpa zea (Lepidoptera: Noctuidae) in Indiana and Illinois.

The corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), can cause serious losses in many field and vegetable crops throughout the United States. Since their introduction, pyrethroid insecticides have become the primary insecticide class for managing H. zea. However, resistance has been reported in the southern United States and has recently became a concern in the Midwest after the observation of sporadic control failures and a decreased efficacy of pyrethroids in small-plot field trials. Larvae collected from Lafayette, IN, Vincennes, IN, and Collinsville, IL, were used to establish laboratory colonies in 2006 and 2007. Larvae from these colonies were tested for resistance to the pyrethroid insecticide bifenthrin by using topical assays. Adult males collected from pheromone traps in Lafayette were tested for resistance to cypermethrin by using the adult vial test (AVT) method. Resistance ratios of > or =8 were observed for the larvalbifenthrin assays in 2006 and 2007 in all colonies except for the 2007 Illinois colony. AVT assays conducted with cypermethrin showed approximately 15% survival in both 2006 and 2007 at the 5 microg per vial discriminating dose. These results suggest that low to moderate levels of pyrethroid resistance are present in these populations.

Turnover of mRNA in prokaryotes and lower eukaryotes.

The turnover of mRNA plays an important role in the regulation of gene expression. The two best understood model systems are those of the prokaryote Escherichia coli and the lower eukaryote Saccharomyces cerevisiae. Considerable progress in recent years has helped define the general pathways by which mRNA is degraded in E coli. Much less is known about the pathways of decay, or the enzymes involved, in eukaryotic cells. However, both cis-acting sequences and trans-acting factors have recently been characterized in S. cerevisiae and an indispensable role for translation has been identified. A comparison of these model species highlights both similarities and differences in mRNA turnover between prokaryotic and eukaryotic systems.

Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs.

In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs requires the decapping enzyme Dcp1p, the 5'-to-3' exoribonuclease Xrn1p, and the three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p. To identify specific functions for the NMD factors, we analyzed the mRNA decay phenotypes of yeast strains containing deletions of DCP1 or XRN1 and UPF1, NMD2, or UPF3. Our results indicate that Upf1p, Nmd2p, and Upf3p regulate decapping and exonucleolytic degradation of nonsense-containing mRNAs. In addition, we show that these factors also regulate the same processes in the degradation of wild-type mRNAs. The participation of the NMD factors in general mRNA degradation suggests that they may regulate an aspect of translation termination common to all transcripts.