Impact of the first response unit on prehospital on-scene time among paramedic-suspected stroke patients: a retrospective before-after cohort study in Finland.

BACKGROUND: Revascularization of an occluded artery by either thrombolysis or mechanical thrombectomy is a time-critical intervention in ischaemic stroke. Each link in the stroke chain of survival should minimize the delay to definitive treatment in every possible way. In this study, we investigated the effect of routine dispatch of a first response unit (FRU) on prehospital on-scene time (OST) on stroke missions. METHODS: Medical dispatch of FRU together with an emergency medical service (EMS) ambulance was a routine strategy in the Tampere University Hospital area before 3 October 2018, after which the FRU has only been dispatched to medical emergencies on the decision of an EMS field commander. This study presents a retrospective before-after analysis of 2,228 paramedic-suspected strokes transported by EMSs to Tampere University Hospital. We collected data from EMS medical records from April 2016 to March 2021, and used statistical tests and binary logistic regression to detect the associations between the variables and the shorter and longer half of OSTs. RESULTS: The median OST of stroke missions was 19 min, IQR [14-25] min. The OST decreased when the routine use of the FRU was discontinued (19 [14-26] min vs. 18 [13-24] min, p < 0.001). The median OST with the FRU being the first at the scene (n = 256, 11%) was shorter than in cases where the FRU arrived after the ambulance (16 [12-22] min vs. 19 [15-25] min, p < 0.001). The OST with a stroke dispatch code was shorter than with non-stroke dispatches (18 [13-23] min vs. 22 [15-30] min, p < 0.001). The OST for thrombectomy candidates was shorter than that for thrombolysis candidates (18 [13-23] min vs. 19 [14-25], p = 0.01). The shorter half of OSTs were associated with the FRU arriving first at the scene, stroke dispatch code, thrombectomy transportation and urban location. CONCLUSION: The routine dispatch of the FRU to stroke missions did not decrease the OST unless the FRU was first to arrive at the scene. In addition, a correct stroke identification in the dispatch centre and thrombectomy candidate status decreased the OST.

Health for All: A Report of the 2020 Association of American Medical Colleges Learn Serve Lead Meeting.

Learn Serve Lead (LSL) is the signature annual conference of the Association of American Medical Colleges (AAMC), which focuses on the most pressing issues facing American medical practice and education. Unsurprisingly, the recent AAMC LSL conference at the end of 2020 centered on the multifaceted impacts of the COVID-19 pandemic and racial inequity upon the medical community. At the LSL meeting, national leaders, practicing physicians from diverse specialties, and medical trainees discussed the impact of these challenges and ongoing strategies to overcome them. These efforts paralleled the AAMC mission areas of community collaborations, medical education, clinical care, and research. Additionally, this focus aligns with the ACR's core purpose: to serve patients and society by empowering members to advance the practice, science, and professions of radiological care. ACR is a member of the AAMC Council of Faculty and Academic Society and seeks to collaborate with other medical specialties to promote interdisciplinary collaboration, contribute to medical education, and voice the value of medical imaging for patient care. We summarize the major insights of this interdisciplinary conference and present tailored recommendations for applying these insights specifically within the radiology community. In addition, we review the parallels between the ACR and the AAMC strategic plans.

Emergency medical dispatchers' ability to identify large vessel occlusion stroke during emergency calls.

BACKGROUND: In acute ischemic stroke, conjugated eye deviation (CED) is an evident sign of cortical ischemia and large vessel occlusion (LVO). We aimed to determine if an emergency dispatcher can recognise LVO stroke during an emergency call by asking the caller a binary question regarding whether the patient's head or gaze is away from the side of the hemiparesis or not. Further, we investigated if the paramedics can confirm this sign at the scene. In the group of positive CED answers to the emergency dispatcher, we investigated what diagnoses these patients received at the emergency department (ED). Among all patients brought to ED and subsequently treated with mechanical thrombectomy (MT) we tracked the proportion of patients with a positive CED answer during the emergency call. METHODS: We collected data on all stroke dispatches in the city of Tampere, Finland, from 13 February 2019 to 31 October 2020. We then reviewed all patient records from cases where the dispatcher had marked 'yes' to the question regarding patient CED in the computer-aided emergency response system. We also viewed all emergency department admissions to see how many patients in total were treated with MT during the period studied. RESULTS: Out of 1913 dispatches, we found 81 cases (4%) in which the caller had verified CED during the emergency call. Twenty-four of these patients were diagnosed with acute ischemic stroke. Paramedics confirmed CED in only 9 (11%) of these 81 patients. Two patients with positive CED answers during the emergency call and 19 other patients brought to the emergency department were treated with MT. CONCLUSION: A small minority of stroke dispatches include a positive answer to the CED question but paramedics rarely confirm the emergency medical dispatcher's suspicion of CED as a sign of LVO. Few patients in need of MT can be found this way. Stroke dispatch protocol with a CED question needs intensive implementation.

Computed Tomography-Guided Microwave Ablation of Cystic Renal Cell Carcinoma: Assessment of Technique and Complications.

This report evaluates the techniques and complications of microwave ablation of cystic renal cell carcinoma. Five patients with cystic renal cell carcinoma were treated with microwave ablation between October 2015 and June 2020. Medical records were reviewed to evaluate technique and complications. Technical success and primary technique efficacy both were 100%. There were no complications. Mean follow-up time was 18 months (range, 6-36 months). No local recurrence was identified during the follow-up period. Renal function remained stable at 1 month and the last follow-up. Percutaneous microwave ablation is promising for the nonsurgical management of cystic renal cell carcinoma.

Effects of physical and cognitive training on gait speed and cognition in older adults: A randomized controlled trial.

Gait speed is a measure of health and functioning. Physical and cognitive determinants of gait are amenable to interventions, but best practices remain unclear. We investigated the effects of a 12-month physical and cognitive training (PTCT) on gait speed, dual-task cost in gait speed, and executive functions (EFs) compared with physical training (PT) (ISRCTN52388040). Community-dwelling older adults, who did not meet physical activity recommendations, were recruited (n = 314). PT included supervised walking/balance (once weekly) and resistance/balance training (once weekly), home exercises (2-3 times weekly), and moderate aerobic activity 150 min/week in bouts of >10 min. PTCT included the PT and computer training (CT) on EFs 15-20 min, 3-4 times weekly. The primary outcome was gait speed. Secondary outcomes were 6-min walking distance, dual-task cost in gait speed, and EF (Stroop and Trail Making B-A). The trial was completed by 93% of the participants (age 74.5 [SD3.8] years; 60% women). Mean adherence to supervised sessions was 59%-72% in PT and 62%-77% in PTCT. Home exercises and CT were performed on average 1.9 times/week. Weekly minutes spent in aerobic activities were 188 (median 169) in PT and 207 (median 180) in PTCT. No significant interactions were observed for gait speed (PTCT-PT, 0.02; 95%CI -0.03, 0.08), walking distance (-3.8; -16.9, 9.3) or dual-task cost (-0.22; -1.74, 1.30). Stroop improvement was greater after PTCT than PT (-6.9; -13.0, -0.8). Complementing physical training with EFs training is not essential for promotion of gait speed. For EF's, complementing physical training with targeted cognitive training provides additional benefit.

Thermal Ablation of Renal Cell Carcinoma in Patients With Morbid Obesity: Assessment of Technique, Safety, and Oncologic Outcomes.

BACKGROUND. Obesity is a worldwide problem that impacts patient health as well as the morbidity associated with surgical procedures. Thus, patients with morbid obesity may not be suitable candidates for curative surgery. For this patient population, thermal ablation may be an effective alternative to nephrectomy. OBJECTIVE. The purpose of this study was to determine the feasibility, oncologic outcomes, and survival of patients with morbid obesity and renal cell carcinoma treated with thermal ablation. MATERIALS AND METHODS. A retrospective analysis was performed of 107 patients treated with CT-guided renal ablation for clinical T1 renal cell carcinoma between February 2005 and December 2017. Patients were stratified into two cohorts on body mass index of ≥ 40 kg/m2 (morbidly obese) and body mass index (weight in kilograms divided by the square of height in meters) of ≥ 40 (morbidly obese) and 18.5-24.9 (normal weight). Anesthetic and radiation dosages, procedure time, residual disease, and local recurrence, and adverse events were analyzed between the two groups. Kaplan-Meier statistics were used to evaluate cancer-related outcomes for each group. RESULTS. Thirty-four patients were morbidly obese, and 73 patients had normal weight. Morbid obesity was associated with longer procedural duration (p = .001), sedative doses (p = .002) and radiation exposure (p = .001) than normal weight. Hematomas were more prevalent in patients with morbid obesity than in those of normal weight (p = .01), but treatment efficacy and local recurrences were comparable with those for normal-weight individuals (p = .81 and p = .12, respectively). Cancer-related outcomes were equivalent between the two groups based on 5 years of imaging observation data. CONCLUSION. CT-guided thermal ablation remains technically feasible, well-tolerated, and effective in patients with morbid obesity and renal cell carcinoma, with the caveat of increased risk of perinephric hematoma, anesthesia dose, and radiation exposure. CLINICAL IMPACT. CT-guided thermal ablation can be considered a safe and effective treatment for renal cell carcinoma in patients with morbid obesity.

Impact of Body Mass Index on Perioperative Complications and Oncologic Outcomes in Patients Undergoing Thermal Ablation for Renal Cell Carcinoma.

PURPOSE: To determine effect of body mass index (BMI) on safety and cancer-related outcomes of thermal ablation for renal cell carcinoma (RRC). MATERIALS AND METHODS: This retrospective study evaluated 427 patients (287 men and 140 women; mean [SD] age, 72 [12] y) who were treated with thermal ablation for RCC between October 2006 and December 2017. Patients were stratified by BMI into 3 categories: normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2). Of 427 patients, 71 (16%) were normal weight, 157 (37%) were overweight, and 199 (47%) were obese. Complication rates, local recurrence, and residual disease were compared in the 3 cohorts. RESULTS: No differences in technical success between normal-weight, overweight, and obese patients were identified (P = .72). Primary technique efficacy rates for normal-weight, overweight, and obese patients were 91%, 94%, and 93% (P = .71). There was no significant difference in RCC specific-free survival, disease-free survival, and metastasis-free survival between obese, overweight, and normal-weight groups (P = .72, P = .43, P = .99). Complication rates between the 3 cohorts were similar (normal weight 4%, overweight 2%, obese 3%; P = .71). CONCLUSIONS: CT-guided renal ablation is safe, feasible, and effective regardless of BMI.

Treatment with gut bifidobacteria improves hippocampal plasticity and cognitive behavior in adult healthy rats.

At the present time, gut microbiota inspires great interest in the field of neuroscience as a function of its role in normal physiology and involvement in brain function. This aspect suggests a specific gut-brain pathway, mainly modulated by gut microbiota activity. Among the multiple actions controlled by microbiota at the brain level, neuronal plasticity and cognitive function represent two of the most interesting aspects of this cross-talk communication. We address the possible action of two-months implementation of gut Bifidobacteria using a mixture of three different strains (B-MIX) on hippocampal plasticity and related cognitive behavior in adult healthy Sprague Dawley rats. B-MIX treatment increases the hippocampal BDNF with a parallel gain in dendritic spines' density of hippocampal CA1 pyramidal neurons. Electrophysiological experiments revealed a significant increment of HFS-induced LTP formation on the CA1 hippocampal region in B-MIX treated rats. All these effects are accompanied by a better cognitive performance observed in B-MIX treated animals with no impairments in locomotion activity. Therefore, in adult rats, the treatment with different strains of bifidobacteria is able to markedly enhance neuronal plasticity and the CNS function influencing cognitive behavior, an effect that may suggest a potential therapeutic treatment in brain diseases associated with cognitive functions.

Social enrichment reverses the isolation-induced deficits of neuronal plasticity in the hippocampus of male rats.

Environmental enrichment is known to improve brain plasticity and protect synaptic function from negative insults. In the present study we used the exposure to social enrichment to ameliorate the negative effect observed in post weaning isolated male rats in which neurotrophic factors, neurogenesis, neuronal dendritic trees and spines were altered markedly in the hippocampus. After the 4 weeks of post-weaning social isolation followed by 4 weeks of reunion, different neuronal growth markers as well as neuronal morphology were evaluated using different experimental approaches. Social enrichment restored the reduction of BDNF, NGF and Arc gene expression in the whole hippocampus of social isolated rats. This effect was paralleled by an increase in density and morphology of dendritic spines, as well as in neuronal tree arborisation in granule cells of the dentate gyrus. These changes were associated with a marked increase in neuronal proliferation and neurogenesis in the same hippocampal subregion that were reduced by social isolation stress. These results further suggest that the exposure to social enrichment, by abolishing the negative effect of social isolation stress on hippocampal plasticity, may improve neuronal resilience with a beneficial effect on cognitive function.

Radiofrequency Ablation, Cryoablation, and Microwave Ablation for T1a Renal Cell Carcinoma: A Comparative Evaluation of Therapeutic and Renal Function Outcomes.

PURPOSE: To compare the therapeutic and renal function outcomes of radiofrequency (RF) ablation, cryoablation, and microwave (MW) ablation for treatment of T1a renal cell carcinoma (RCC). MATERIALS AND METHODS: A retrospective assessment of 297 patients (mean age 72 years range 24-90 years) with biopsy-proven RCC treated with image-guided percutaneous thermal ablation was performed between October 2006 and December 2016. Mean tumor size was 2.4 cm; mean radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, hilar tumor touching the main renal artery or vein, and location relative to polar lines; Preoperative Aspects and Dimensions Used for an Anatomical; and c-centrality scores were 6.0, 7.0, and 2.8, respectively. Assessments of adverse events, treatment efficacy, and therapeutic outcomes were performed among RF ablation, cryoablation, and MW ablation. The 2-year disease-free, metastatic-free, and cancer-specific survival rates were tabulated. Estimated glomerular filtration rate was used to assess for treatment related changes in renal function. RESULTS: A total of 297 T1aN0M0 biopsy-proven RCCs measuring 1.2-3.9 cm were treated with computed tomography-guided RF ablation (n = 244, 82%), cryoablation (n = 26, 9%), and MW ablation (n = 27, 9%). There were no significant differences in patient demographics among the 3 groups (P = .09). Technical success rates were similar among the 3 treatments (P = .33). Primary efficacy at 1 month postablation was more likely to be achieved with RF ablation and MW ablation than with cryoablation. At 2 years' follow-up, there was no local recurrence, metastatic progression, or RCC-related death observed in the 3 groups. There was no significant change in estimated glomerular filtration rate among the 3 ablation groups compared with baseline at 2-year follow-up (P = .71). CONCLUSION: RF ablation, cryoablation, and MW ablation are equivalent at 2 years for treatment of T1a RCC for therapeutic outcome, stability of renal function, and low adverse event rate.

Professional firefighter and trained volunteer first-responding units in emergency medical service.

BACKGROUND: Although widely dispatched to out-of-hospital cardiac arrests, the performance of prehospital first-responding units in other medical emergencies is unknown. METHODS: In this retrospective, descriptive study, the general performance of 44 first-responding units in Pirkanmaa County, Finland, were examined. A subgroup analysis compared the first-responding units made up of professional firefighters and trained volunteers. RESULTS: First-responding units were dispatched to patients during 1622 missions between 1 January 2013 and 31 December 2013. The median time to reach the scene was 9 minutes in any mission. Overall, first responders evaluated 1015 patients and provided treatment or assisted ambulance personnel in 793 (78%) cases. The most common treatment modalities were assistance, such as carrying (22%) and the administration of supplemental oxygen (19%). There were 83 resuscitation attempts during the time period. In 42 of these, first-responding units initiated basic life support a median of 4 minutes prior to the arrival of ambulance personnel. Return of spontaneous circulation was achieved in 20% of cases. The subgroup analysis showed that trained volunteers administered oxygen more liberally than professional firefighters in stroke and chest pain mission (stroke: professional 9/236 cases [4%] vs layperson 26/181 cases [14%], P < 0.001; chest pain: professional 16/78 cases [21%] vs layperson 77/159 cases [48%], P < 0.001). CONCLUSION: First-responding units provided initial treatment or assistance to ambulance personnel in approximately half of the missions. Implementation of professional- and layperson-staffed first-responding units in emergency medical service system seems to be feasible.

Risk Assessment of Chronic Kidney Disease following Microwave Ablation for Stage T1 Renal Cell Carcinoma.

PURPOSE: To assess safety and renal-function outcomes after microwave (MW) ablation of localized stage T1 renal cell carcinoma (RCC). MATERIALS AND METHODS: A retrospective review was conducted of 38 patients (28 men; mean age, 69 y; range, 51-88 y) who underwent computed tomography (CT)-guided MW ablation for stage T1N0M0 RCC. Baseline and follow-up renal function surrogates including creatinine level and estimated glomerular filtration rate (eGFR) were statistically compared. Peri- and postoperative complication rates, technical success, and treatment response were also assessed. RESULTS: A total of 44 biopsy-proven stage T1N0M0 RCCs measuring 1.2-6.9 cm (mean, 2.5 cm) were treated, and renal function was measured 1 mo after treatment. Mean eGFRs were 60 mL/min/1.73 m2 at baseline and 59 mL/min/1.73 m2 at 1 month after ablation. At 1-year and last follow-ups, the means of difference were 3.3% (95% confidence interval, -4.4 to 4.3; P = .99) and 3.3% (95% confidence interval, -4.3 to 4.8; P = .91), respectively. The 2-years freedom from eGFR decrease to < 60 mL/min/1.73 m2 was 2% (P = .91). Among the 5 patients (13%) with preexisting stage 4 chronic kidney disease (CKD; eGFR < 30 mL/min/1.73 m2) before ablation, there was no significant postablative onset of decline or CKD upstaging (P = .001). There were no major complications, and 5 patients (13%) had small asymptomatic perinephric hematomas (Society of Interventional Radiology minor complication, class A/B) that were managed conservatively. CONCLUSIONS: At 2-year follow-up, CT-guided percutaneous MW ablation is safe and well-tolerated and achieves nephron preservation similar to existing ablative modalities.

Promoting safe walking among older people: the effects of a physical and cognitive training intervention vs. physical training alone on mobility and falls among older community-dwelling men and women (the PASSWORD study): design and methods of a randomized controlled trial.

BACKGROUND: Safe and stable walking is a complex process involving the interaction of neuromuscular, sensory and cognitive functions. As physical and cognitive functions deteriorate with ageing, training of both functions may have more beneficial effects on walking and falls prevention than either alone. This article describes the study design, recruitment strategies and interventions of the PASSWORD study investigating whether a combination of physical and cognitive training (PTCT) has greater effects on walking speed, dual-task cost in walking speed, fall incidence and executive functions compared to physical training (PT) alone among 70-85-year-old community-dwelling sedentary or at most moderately physically active men and women. METHODS: Community-dwelling sedentary or at most moderately physically active, men and women living in the city of Jyväskylä will be recruited and randomized into physical training (PT) and physical and cognitive training (PTCT). The 12-month interventions include supervised training sessions and home exercises. Both groups attend physical training intervention, which follows the current physical activity guidelines. The PTCT group performes also a web-based computer program targeting executive functions. Outcomes will be assessed at baseline and at 6 and 12 months thereafter. Falls data are collected during the interventions and the subsequent one-year follow-up. The primary outcome is 10-m walking speed. Secondary outcomes include 6-min walking distance, dual-task cost in walking speed, fall incidence and executive function assessed with color Stroop and Trail Making A and B tests. Explanatory outcomes include e.g. body composition and bone characteristics, physical performance, physical activity, life-space mobility, fall-related self-efficacy, emotional well-being and personality characteristics. DISCUSSION: The study is designed to capture the additive and possible synergistic effects of physical and cognitive training. When completed, the study will provide new knowledge on the effects of physical and cognitive training on the prevention of walking limitations and rate of falls in older people. The expected results will be of value in informing strategies designed to promote safe walking among older people and may have a significant health and socio-economic impact. TRIAL REGISTRATION: ISRCTN52388040 .

Spatial diffusion of surnames by long transhumance routes between highland and lowland: A study in Sardinia.

RIASSUNTO.

Image-Guided Thermal Ablation for Non-resectable Recurrence of Renal Cell Cancer Following Nephrectomy: Clinical Experience with Eleven Patients.

PURPOSE: To assess the feasibility, safety and clinical outcomes of image-guided percutaneous thermal ablation as salvage therapy for local recurrence of renal cell carcinoma (RCC) in patients initially treated surgically with curative intent. MATERIALS AND METHODS: A retrospective review of 11 consecutive patients (M/F = 8:3, mean age = 76 years) who underwent computed tomography (CT)-guided thermal ablation for locally recurrent RCC after partial (72%, 8/11) or radical nephrectomy (28%, 3/11) with a mean time to recurrence of 48 months (range 2-156). Assessment of technical success, complication (peri- and post-procedural), oncological outcome and survival analysis were performed. Patient baseline and follow-up renal function surrogates including creatinine level (Cr) and estimated glomerular filtration rate (eGFR) were statistically compared. RESULTS: Eleven biopsy-proven recurrent RCC measuring 1.4-3.9 cm (mean = 2.8 cm) were treated with CT-guided thermal ablation. Technical success was achieved in 100% (11/11) of the cases. There were no major complications except for one (9%) asymptomatic hemorrhage (Clavien-Dindo grade I complication). Complete response, local progression-free and overall survival rate were 91, 91 and 82% during the mean follow-up time of 2.5 years (range 0.1-7.1). Renal function was overall stable without significant change at 1 month and last follow-up (p = 0.21; GFR, p = 0.10; creatinine). CONCLUSIONS: Image-guided percutaneous thermal ablation is a feasible, safe and effective for local recurrence after nephrectomy, representing a non-surgical alternative for unresectable disease.

Emotional responses of clients to veterinarian communication style during a vaccination visit in companion animal practice.

OBJECTIVE To study the effects of veterinarian communication (ie, the information provided and gaze and body direction) and vaccination style on the emotions and physiologic reactions experienced by clients and on clients' evaluation of the expertise and trustworthiness of the veterinarian. DESIGN Simulation study. PARTICIPANTS 20 small animal clients. PROCEDURES Participants were shown 12 videos of a female veterinarian in which she first provided information about puppy vaccination and then performed the procedure. The veterinarian's behavior varied regarding the information provided about the vaccination (ie, scarce, factual, or emotional), her gaze and body direction (ie, direct or 30° averted), and her vaccination style (ie, routine or emotional). While the participants watched the videos, their corrugator supercilii muscle activity (corrugator supercilii muscles are activated when frowning) and skin conductance activity were measured. Participants also rated the emotions they experienced (ie, valence and arousal) and assessed the veterinarian's behavior (ie, expertise and trustworthiness). RESULTS Overall, emotional information, a direct gaze and body direction, and an emotional vaccination style were associated with more pleasant emotions and higher ratings of the expertise and trustworthiness of the veterinarian's behavior by clients. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that through certain behavioral actions, veterinarians may positively affect the emotions and feelings experienced by clients during veterinary clinic visits, even in the case of vaccination visits, which can be considered routine visits from the viewpoint of the veterinarian.

Lead isotopic fingerprint in human scalp hair: The case study of Iglesias mining district (Sardinia, Italy).

The Sulcis-Iglesiente district (SW Sardinia, Italy) has been, until recently, one of the most important Italian polymetallic mining areas for the extraction of lead. Epidemiological studies conducted over several decades have indicated this site at high risk of environmental crisis with possible adverse effects on the public health. In the present paper we discuss Pb isotope signatures in human scalp hair and road dust collected from the Sulcis-Iglesiente area in order to trace the exposure of populations to potential Pb sources. A total of 23 determinations (20 on hair samples and 3 on road dust samples) of lead isotope ratios (206Pb/207Pb and 208Pb/206Pb) were carried out. The obtained results were integrate with literature data regarding the total content of Pb in hair samples from the same study area. Hair from children living in Sant'Antioco exhibited lead isotope ratios in the ranges 1.152-1.165 for 206Pb/207Pb and 2.101-2.108 for 208Pb/206Pb, while hair samples from Iglesias resulted less radiogenic: 206Pb/207Pb~1.147-1.154 and 208Pb/206Pb~2.106-2.118. These values pointed to a multi-source mixing between the less radiogenic sources, corresponding to the Pb ore deposits, and the more radiogenic sources identified in local background.

The two transmembrane regions of Candida albicans Dfi1 contribute to its biogenesis.

The opportunistic pathogen Candida albicans forms invasive filaments that grow into host tissues during disease. The glycosylated, integral plasma membrane protein Dfi1 is important for invasive filamentation in a laboratory model, and for lethality in murine disseminated candidiasis. However, Dfi1 topology and essential domains for Dfi1 biogenesis were undefined. Sequence analysis predicted that Dfi1 contains two transmembrane regions, located near the N- and C-termini. In this communication, we show that Dfi1 remains an integral membrane protein despite deletion of either predicted transmembrane region, whereas deletion of both regions results in a soluble protein. Additionally, Dfi1 that was properly oriented in the membrane, as indicated by N-linked glycosylation, was observed when either transmembrane region was deleted, but was absent when both transmembrane regions were deleted. Interestingly, deletion of the N-terminal transmembrane region resulted in production of two forms of Dfi1. Most of the protein molecules acquired normal N-linked glycosylation and a smaller population failed to become normally N-linked glycosylated. This defect was reversed by replacement of the N-terminal hydrophobic sequence with one synthetic transmembrane sequence but not another. Finally, microscopy studies revealed that Dfi1 lacking the N-terminal transmembrane region was observed at the cell periphery, where full-length Dfi1 normally localizes, whereas the double-truncation mutant was diffusely intracellular. Therefore, mature Dfi1 protein contains two transmembrane domains which contribute to its biogenesis.