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America's scientific success is no accident. It has been powered by a decades-long commitment to federal investment in fundamental research that, in turn, nurtured both domestic and foreign talent and prompted the translation of breakthroughs to fuel the economy, improve health, fortify national security, and inspire awe. The world has benefited from the proliferation of this model, and partnerships between the US and other countries have resulted in game-changing discoveries, from medicines to machine learning. Yet what got America to this point will not get the country to where it needs to go. A new vision is required to respond to an evolving global science and technology ecosystem.

Objective: This study aims to identify distinguishing MRI features of Lyme arthritis (LA), an increasingly prevalent cause of pediatric infectious arthritis in the USA, to enable rapid discrimination from septic arthritis (SA) and facilitate appropriate management., Materials and Methods: A single-center, retrospective analysis was conducted on a convenience sample of pediatric patients with LA in an endemic area using EPIC electronic health record data between January 2010 and December 2020. Patients with positive serologic testing and concurrent MRI were selected. MRI scans were reviewed by a subspecialty-trained pediatric radiologist. Key MRI features analyzed include joint effusion, synovitis, myositis, soft tissue edema, and osseous edema and erosions. MRI features, demographics, and clinical data were compared using univariable and multivariable analyses., Results: Fifty cases of knee LA and 13 cases of knee SA were included. Larger joint effusion (p = 0.0055, z =  - 2.779) and abnormally thickened synovium (p = 0.0011, χ 2  = 10.622) were more associated with LA. In contrast, increased myositis, subcutaneous edema, and osseous changes were more prevalent in SA. Abnormal bone marrow signal (p < 0.0001, χ 2  = 36.893) and bone erosion (p < 0.0001, χ 2  = 25.506) were observed in 84.6% (11/13) and 46.2% (6/13) of SA cases, respectively, while no bone erosion was found in LA., Conclusion: MRI can be a valuable tool in differentiating LA from SA. Abnormal synovium and increasing joint effusion favor LA, while increasing soft tissue edema and osseous changes favor SA. Notably, the presence of bone erosion effectively excluded LA from consideration., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Competing Interests: Disclosures None.

Phytoremediation, a cost-effective, eco-friendly alternative to conventional remediation, could expand efforts to remediate arsenic-contaminated soils. As with other pollutants, the plant microbiome may improve phytoremediation outcomes for arsenic-contaminated sites. We used in vitro and in silico methods to compare the arsenic resistance mechanisms, synthesis of extracellular polymeric substances (EPS), biofilm formation, and plant growth-promoting abilities of the endophytes Pseudomonas sp. PD9R and Rahnella laticis PD12R. PD12R, which tolerates arsenate (As(V)) and arsenite (As(III)) to concentrations fivefold greater than PD9R, synthesizes high volumes of EPS in response to arsenic, and sequesters arsenic in the capsular EPS and cells. While arsenic exposure induced EPS synthesis in both strains, only PD12R continued to form biofilms at high As(III) and As(V) concentrations. The effects of endophyte inoculation on Arabidopsis growth varied by strain and As(V) concentration, and PD9R had positive effect on plants exposed to low levels of arsenic. Comparative genomic analyses exploring the EPS synthesis and arsenic resistance mechanisms against other Pseudomonas and Rahnella strains suggest that both strains possess atypical arsenic resistance mechanisms from other plant-associated strains, while the configuration of the EPS synthesis systems appeared to be more broadly distributed among plant- and non-plant-associated strains.

The plant microbiome can be used to bolster plant defense against abiotic and biotic stresses. Some strains of endophytes, the microorganisms within plants, can directly inhibit the growth of plant fungal pathogens. A previously isolated endophyte from wild Populus (poplar), WPB of the species Burkholderia vietnamiensis , had robust in vitro antifungal activity against pathogen strains that are highly virulent and of concern to Pacific Northwest agriculture: Rhizoctonia solani AG-8, Fusarium culmorum 70110023, and Gaemannomyces graminis var. tritici (Ggt) ARS-A1, as well as activity against the oomycete, Pythium ultimum 217. A direct screening method was developed for isolation of additional anti-fungal endophytes from wild poplar extracts. By challenging pathogens directly with dilute extracts, eleven isolates were found to be inhibitory to at least two plant pathogen strains and were therefore chosen for further characterization. Genomic analysis was conducted to determine if these endophyte strains harbored genes known to be involved in antimicrobial activities. The newly isolated Bacillus strains had gene clusters for production of bacillomycin, fengicyn, and bacillibactin, while the gene cluster for the synthesis of sessilin, viscosin and tolaasin were found in the Pseudomonas strains. The biosynthesis gene cluster for occidiofungin ( ocf ) was present in the Burkholderia vietnamiensis WPB genome, and an ocf deletion mutant lost inhibitory activity against 3 of the 4 pathogens. The new isolates lacked the gene cluster for occidiofungin implying they employ different modes of action. Other symbiotic traits including nitrogen fixation, phosphate solubilization, and the production of auxins and siderophores were investigated. Although it will be necessary to conduct in vivo tests of the candidates with pathogen-infected agricultural crops, the wild poplar tree microbiome may be a rich source of beneficial endophyte strains with potential for biocontrol applications against a variety of pathogens and utilizing varying modes of action.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal cardiac arrhythmia syndrome triggered by catecholamines released during exercise, stress, or sudden emotion. Variants in the calsequestrin-2 gene ( CASQ2 ), encoding the major calcium (Ca) binding protein in the sarcoplasmic reticulum (SR), are the second most common cause of CPVT. Recently, several CASQ2 gene variants, such as CASQ2 -K180R, have been linked to an autosomal dominant form of Casq2-linked CPVT (CPVT2), but the underlying mechanism is not known., Methods: A K180R mouse model was generated using CRIPSR/Cas9. Heterozygous and homozygous K180R mice were studied using telemetry ECG recordings in vivo. Ventricular cardiomyocytes were isolated and studied using fluorescent Ca indicators and patch clamp. Expression levels and localization of SR Ca-handling proteins were evaluated using Western blotting and immunostaining. Intra-SR Ca kinetics were quantified using low-affinity Ca indicators., Results: K180R mice exhibit an autosomal dominant CPVT phenotype following exercise or catecholamine stress. Upon catecholamine stress, K180R ventricular cardiomyocytes exhibit increased spontaneous SR Ca release events, triggering delayed afterdepolarizations and spontaneous beats. K180R had no effect on levels of Casq2, Casq2 polymers, or other SR Ca-handling proteins. Intra-SR Ca measurements revealed that K180R impaired dynamic intra-SR Ca buffering, resulting in a more rapid rise of free Ca in the SR during diastole. Steady-state SR Ca buffering and total SR Ca content were not changed. Consistent with the reduced dynamic intra-SR buffering, K180R causes reduced SR Ca release refractoriness., Conclusions: CASQ2-K180R causes CPVT2 via a heretofore unknown mechanism that differs from CASQ2 variants associated with autosomal recessive CPVT2. Unlike autosomal recessive CASQ2 variants, K180R impairs the dynamic buffering of Ca within the SR without affecting total SR Ca content or Casq2 protein levels. Our data provide insight into the molecular mechanism underlying autosomal dominant CPVT2.

Objective: To investigate the relationship between maximal exercise capacity measured before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalization due to coronavirus disease 2019 (COVID-19)., Methods: We identified patients (≥18 years) who completed a clinically indicated exercise stress test between January 1, 2016, and February 29, 2020, and had a test for SARS-CoV-2 (ie, real-time reverse transcriptase polymerase chain reaction test) between February 29, 2020, and May 30, 2020. Maximal exercise capacity was quantified in metabolic equivalents of task (METs). Logistic regression was used to evaluate the likelihood that hospitalization secondary to COVID-19 is related to peak METs, with adjustment for 13 covariates previously identified as associated with higher risk for severe illness from COVID-19., Results: We identified 246 patients (age, 59±12 years; 42% male; 75% black race) who had an exercise test and tested positive for SARS-CoV-2. Among these, 89 (36%) were hospitalized. Peak METs were significantly lower (P<.001) among patients who were hospitalized (6.7±2.8) compared with those not hospitalized (8.0±2.4). Peak METs were inversely associated with the likelihood of hospitalization in unadjusted (odds ratio, 0.83; 95% CI, 0.74-0.92) and adjusted models (odds ratio, 0.87; 95% CI, 0.76-0.99)., Conclusion: Maximal exercise capacity is independently and inversely associated with the likelihood of hospitalization due to COVID-19. These data further support the important relationship between cardiorespiratory fitness and health outcomes. Future studies are needed to determine whether improving maximal exercise capacity is associated with lower risk of complications due to viral infections, such as COVID-19., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Commercial genetic testing for long QT syndrome (LQTS) has rapidly expanded, but the inability to accurately predict whether a rare variant is pathogenic has limited its clinical benefit. Novel missense variants are routinely reported as variant of unknown significance (VUS) and cannot be used to screen family members at risk for sudden cardiac death. Better approaches to determine the pathogenicity of VUS are needed., Objective: The purpose of this study was to rapidly determine the pathogenicity of a CACNA1C variant reported by commercial genetic testing as a VUS using a patient-independent human induced pluripotent stem cell (hiPSC) model., Methods: Using CRISPR/Cas9 genome editing, CACNA1C-p.N639T was introduced into a previously established hiPSC from an unrelated healthy volunteer, thereby generating a patient-independent hiPSC model. Three independent heterozygous N639T hiPSC lines were generated and differentiated into cardiomyocytes (CM). Electrophysiological properties of N639T hiPSC-CM were compared to those of isogenic and population control hiPSC-CM by measuring the extracellular field potential (EFP) of 96-well hiPSC-CM monolayers and by patch clamp., Results: Significant EFP prolongation was observed only in optically stimulated but not in spontaneously beating N639T hiPSC-CM. Patch-clamp studies revealed that N639T prolonged the ventricular action potential by slowing voltage-dependent inactivation of Ca V 1.2 currents. Heterologous expression studies confirmed the effect of N639T on Ca V 1.2 inactivation., Conclusion: The patient-independent hiPSC model enabled rapid generation of functional data to support reclassification of a CACNA1C VUS to likely pathogenic, thereby establishing a novel LQTS type 8 mutation. Furthermore, our results indicate the importance of controlling beating rates to evaluate the functional significance of LQTS VUS in high-throughput hiPSC-CM assays., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: Percutaneous nephrolithotomy (PCNL) is a complex multistep surgery that has shown a steady increase in use for the past decade in the United States. We sought to evaluate the trends and factors associated with PCNL usage across New York State (NYS). Our goal was to characterize patient demographics and socioeconomic factors across high-, medium-, and low-volume institutions. Materials and Methods: We searched the NYS, Statewide Planning and Research Cooperative System (SPARCS) database from 2006 to 2014 using ICD-9 Procedure Codes 55.04 (percutaneous nephrostomy with fragmentation) for all hospital discharges. Patient demographics including age, gender, race, insurance status, and length of hospital stay were obtained. We characterized each hospital as a low-, medium-, or high-volume center by year. Patient and hospital demographics were compared and reported using chi-square analysis and Student's t -test for categorical and continuous variables, respectively, with statistical significance as a p -value of <0.05. Results: We identified a total of 4576 procedures performed from 2006 to 2014 at a total of 77 hospitals in NYS (Table 1). Total PCNL volume performed across all NYS hospitals increased in the past decade, with the greatest number of procedures performed in 2012 to 2013. Low-volume institutions were more likely to provide care to minority populations (21.4% vs 17.3%, p  < 0.001) and those with Medicaid (25.5% vs 21.5%, p  < 0.001). High-volume institutions provided care to patients with private insurance (42.1% vs 34.0%, p  < 0.001) and had a shorter length of stay (3.3 days vs 4.1 days, p  < 0.001). Conclusion: Our data provide insight into the patient demographics of those treated at high-, medium-, and low-volume hospitals for PCNL across NYS. Significant differences in race, insurance status, and length of stay were noted between low- and high-volume institutions, indicating that racial and socioeconomic factors play a role in access to care at high-volume centers.

Background and Rationale: Obesity, an independent risk factor for the development of myocardial diseases is a growing healthcare problem worldwide. It's well established that GSK-3β is critical to cardiac pathophysiology. However, the role cardiomyocyte (CM) GSK-3β in diet-induced cardiac dysfunction is unknown., Methods: CM-specific GSK-3β knockout (CM-GSK-3β-KO) and littermate controls (WT) mice were fed either a control diet (CD) or high-fat diet (HFD) for 55weeks. Cardiac function was assessed by transthoracic echocardiography., Results: At baseline, body weights and cardiac function were comparable between the WT and CM-GSK-3β-KOs. However, HFD-fed CM-GSK-3β-KO mice developed severe cardiac dysfunction. Consistently, both heart weight/tibia length and lung weight/tibia length were significantly elevated in the HFD-fed CM-GSK-3β-KO mice. The impaired cardiac function and adverse ventricular remodeling in the CM-GSK-3β-KOs were independent of body weight or the lean/fat mass composition as HFD-fed CM-GSK-3β-KO and controls demonstrated comparable body weight and body masses. At the molecular level, on a CD, CM-GSK-3α compensated for the loss of CM-GSK-3β, as evident by significantly reduced GSK-3αs21 phosphorylation (activation) resulting in a preserved canonical β-catenin ubiquitination pathway and cardiac function. However, this protective compensatory mechanism is lost with HFD, leading to excessive accumulation of β-catenin in HFD-fed CM-GSK-3β-KO hearts, resulting in adverse ventricular remodeling and cardiac dysfunction., Conclusion: In summary, these results suggest that cardiac GSK-3β is crucial to protect against obesity-induced adverse ventricular remodeling and cardiac dysfunction., (Copyright © 2018 Elsevier Ireland Ltd. All rights reserved.)

Efficient storing and retrieval of medical images has direct impact on reducing costs and improving access in cloud-based health care services. JPEG 2000 is currently the commonly used compression format for medical images shared using the DICOM standard. However, new formats such as high efficiency video coding (HEVC) can provide better compression efficiency compared to JPEG 2000. Furthermore, JPEG 2000 is not suitable for efficiently storing image series and 3-D imagery. Using HEVC, a single format can support all forms of medical images. This paper presents the use of HEVC for diagnostically acceptable medical image compression, focusing on compression efficiency compared to JPEG 2000. Diagnostically acceptable lossy compression and complexity of high bit-depth medical image compression are studied. Based on an established medically acceptable compression range for JPEG 2000, this paper establishes acceptable HEVC compression range for medical imaging applications. Experimental results show that using HEVC can increase the compression performance, compared to JPEG 2000, by over 54%. Along with this, a new method for reducing computational complexity of HEVC encoding for medical images is proposed. Results show that HEVC intra encoding complexity can be reduced by over 55% with negligible increase in file size.

Self-regulation is a broad construct representing the general ability to recruit cognitive, motivational and emotional resources to achieve long-term goals. This construct has been implicated in a host of health-risk behaviors, and is a promising target for fostering beneficial behavior change. Despite its clear importance, the behavioral, psychological and neural components of self-regulation remain poorly understood, which contributes to theoretical inconsistencies and hinders maximally effective intervention development. We outline a research program that seeks to define a neuropsychological ontology of self-regulation, articulating the cognitive components that compose self-regulation, their relationships, and their associated measurements. The ontology will be informed by two large-scale approaches to assessing individual differences: first purely behaviorally using data collected via Amazon's Mechanical Turk, then coupled with neuroimaging data collected from a separate population. To validate the ontology and demonstrate its utility, we will then use it to contextualize health risk behaviors in two exemplar behavioral groups: overweight/obese adults who binge eat and smokers. After identifying ontological targets that precipitate maladaptive behavior, we will craft interventions that engage these targets. If successful, this work will provide a structured, holistic account of self-regulation in the form of an explicit ontology, which will better clarify the pattern of deficits related to maladaptive health behavior, and provide direction for more effective behavior change interventions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Rationale: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM, including lack of T-tubules, immature excitation-contraction coupling, and inefficient Ca-induced Ca release remain major limitations., Objective: Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote T-tubule development and mature excitation-contraction coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress)., Methods and Results: hiPSC-CM were generated using a standard chemical differentiation method supplemented with T3 (triiodothyronine) and/or Dex (dexamethasone) during days 16 to 30 followed by single-cell culture for 5 days on Matrigel mattress. hiPSC-CM treated with T3+Dex, but not with either T3 or Dex alone, developed an extensive T-tubule network. Notably, Matrigel mattress was necessary for T-tubule formation. Compared with adult human ventricular cardiomyocytes, T-tubules in T3+Dex-treated hiPSC-CM were less organized and had more longitudinal elements. Confocal line scans demonstrated spatially and temporally uniform Ca release that is characteristic of excitation-contraction coupling in the heart ventricle. T3+Dex enhanced elementary Ca release measured by Ca sparks and promoted RyR2 (ryanodine receptor) structural organization. Simultaneous measurements of L-type Ca current and intracellular Ca release confirmed enhanced functional coupling between L-type Ca channels and RyR2 in T3+Dex-treated cells., Conclusions: Our results suggest a permissive role of combined thyroid and glucocorticoid hormones during the cardiac differentiation process, which when coupled with further maturation on Matrigel mattress, is sufficient for T-tubule development, enhanced Ca-induced Ca release, and more ventricular-like excitation-contraction coupling. This new hormone maturation method could advance the use of hiPSC-CM for disease modeling and cell-based therapy., (© 2017 American Heart Association, Inc.)

Context: The Proseal LMA(PLMA), which has been designed especially for positive pressure ventilation and protection against aspiration can act as an alternative to Endotracheal Tube (ETT) as an effective airway device for patients undergoing elective Laparoscopic surgeries., Aims: To compare the efficacy and safety of PLMA with ETT in patients undergoing Laparoscopic surgeries under general anaesthesia., Settings and Design: A prospective, randomized study was conducted in a tertiary care teaching hospital with 60 patients of ASA grade I/II undergoing elective Laparoscopic surgery under general anaesthesia. Ethical committee clearance and written consent taken. The patients were randomly divided into two equal groups to the PLMA group (Group S) and to the ETT group (Group C) Heart rate (HR), mean blood pressure (MAP), ETCO 2 values, intraoperative complications such as regurgitation- aspiration, and Postoperative complications such as nausea or vomiting, throat soreness and oral injuries were monitored., Results: There was no difference demographically. Insertion success rate was 100% for both the groups. The mean increase in HR was seen all throughout the duration of the surgery to 8 % above the baseline in Group C and to 3% above the baseline in Group S. On comparing the MAP in Group C, there was a increased by 2.5% to 78.300 ± 14.2615 mmHg as compared to an increase by 5% to 76.233 ± 6.2072 mmHg in Group S. EtCO2 showed a rise in both groups after pneumoperitoneum, which returned to baseline values after completion of surgery. Gastric aspirate values showed no difference in each group. Post op complications were seen mainly in Group C with statistical significance., Conclusions: A properly positioned PLMA is a suitable and safe alternative to ETT for airway management in adequately fasted, adult patients undergoing elective Laparoscopic surgeries., Competing Interests: There are no conflicts of interest.

Aims: To evaluate the efficacy of intrathecal isobaric Ropivacaine and its comparison with intrathecal isobaric Bupivacaine in elective inguinal hernia repair surgeries., Settings and Design: A prospective, randomized study was conducted in a tertiary care hospital with 80 patients of ASA grade I-III undergoing elective inguinal hernia repair surgery under spinal anaesthesia. Ethical committee clearance and written consent taken. The patients were randomly divided into two equal groups to the Ropivicaine group (Group R) and to theBupivicaine group (Group B). Parameters observed were onset and duration of sensory and motor block, maximum sensory level achieved degree of motor blockade, two segment regression, and haemodynamic changes., Results: The development of sensory block was faster with Isobaric Ropivicaine (12.1 ± 4.9 minutes) as than isobaric Bupivicaine (13.94 ± 4.52 minutes) but the difference was not statistically significant. Onset of Grade III Motor block was longer with Isobaric Ropivicaine (8.51 ± 3.39 minutes) as compared to isobaric Bupivicaine (8.51 ± 3.39 minutes), but the difference was not statistically significant. Time of Complete Sensory Regression was significantly shorter with Isobaric Ropivicaine (212.69 ± 27.31 minutes) with statistical significance. Time to complete motor recovery was significantly shorter in Ropivacaine group (253.38 ± 27.13 minutes)as compared to Bupivacaine group (258.55 ± 35.81min), with statistical significance. Time to achieve discharge criteria was relatively shorter with Isobaric Ropivicaine. Haemodynamic Parameters did not differ significantly in both the groups during the entire study period., Conclusion: Intrathecal administration of isobaric Ropivacaine (0.75%) 15 mg provides similar quality of spinal anaesthesia but of significantly shorter duration, maintaining similar hemodynamic stability and discharge criteria without significant adverse effects when compared to isobaric Bupivicaine (0.5%) 10 mg., Competing Interests: There are no conflicts of interest.

Introduction: Endometriosis is defined as the presence of functional ectopic endometrial tissue outside the uterine cavity. It rarely involves the small bowel and obstruction due to the same is highly uncommon. Preoperative diagnosis is difficult based on clinical and radiological studies. Diagnosis can be confirmed only on histopathological examination of the surgically resected specimen., Presentation of Case: A 44 years old lady presented with repeated episodes of abdominal pain, non bilious vomiting and diarrhea. She also gave history of abdominal pain during every menstruation. She had diffuse abdominal tenderness and the computed tomography showed a concentric infective/inflammatory thickening of the distal ileum. Colonoscopy confirmed a tight distal ileal stricture After a failed trial of conservative management, she underwent a laparoscopic right hemicolectomy. The histopathological examination revealed multiple endometriotic foci in the ileum and the appendix., Discussion: Ileal endometriosis presenting as obstruction is uncommon and very few cases have been reported thus far. The symptoms are usually cyclical but may later become continuous with the progression of the disease. Preoperative diagnostic dilemma is due to the clinical and the radiological similarities to inflammatory, infective and irritable bowel diseases., Conclusion: Ours is probably the first case of small bowel obstruction due to ileal and appendiceal endometriosis that was managed with laparoscopic right hemicolectomy. We highlight the preoperative diagnostic dilemma and the progression of the cyclical symptoms. Thus, endometriosis must be considered in cases of small bowel obstruction in women in the reproductive age group as a rare cause., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Modern facelift techniques have benefited from a "repopularization" of shorter incisions, limited skin elevation, and more limited dissection of the superficial musculoaponeurotic system (SMAS) and platysma in order to shorten postoperative recovery times and reduce surgical risks for patients., Objectives: The authors describe their minimal access deep plane extended (MADE) vertical vector facelift, which is a hybrid technique combining the optimal features of the deep plane facelift and the short scar, minimal access cranial suspension (MACS) lift., Methods: The authors retrospectively reviewed the case records of 181 patients who underwent facelift procedures performed by the senior author (AAJ) during a two year period between March 2008 and March 2010. Of those patients, 153 underwent facelifting with the MADE vertical technique. With this technique, deep plane dissection releases the zygomatico-cutaneous ligaments, allowing for more significant vertical motion of the midface and jawline during suspension. Extended platysmal dissection was utilized with a lateral platysmal myotomy, which is not traditionally included in a deep plane facelift. The lateral platysmal myotomy allowed for separation of the vertical vector of suspension in the midface and jawline from the superolateral vector of suspension that is required for neck rejuvenation, obviating the need for additional anterior platysmal surgery., Results: The average age of the patients was 57.8 years. The average length of follow-up was 12.7 months. In 69 consecutive patients from this series, average vertical skin excision measured 3.02 cm on each side of the face at the junction of the pre auricular and temporal hair tuft incision (resulting in a total excision of 6.04 cm of skin). Data from the entire series revealed a revision rate of 3.9%, a hematoma rate of 1.9%, and a temporary facial nerve injury rate of 1.3%., Conclusions: The common goal of all facelifting procedures is to provide a long-lasting, natural, balanced, rejuvenated aesthetic result with few complications and minimal downtime. The MADE vertical facelift fulfills these criteria and often yields superior results in the midface and neck areas, where many short scar techniques fail. Furthermore, this procedure can be performed under local anesthesia, which is a benefit to both patients and surgeons.

Objectives: To quantify the degree of submental platysmal tightening that can be accomplished with superficial musculoaponeurotic system (SMAS) plication vs deep-plane rhytidectomy techniques in a cadaveric anatomical study to help dictate the need for midline platysmal surgery when using different rhytidectomy techniques., Methods: The lateral distraction of the medial edge of the platysma muscle was measured during tightening of the SMAS-platysmal complex on 5 cadaver heads. The measurements were taken after the following 3 rhytidectomy techniques: SMAS-platysmal plication, deep-plane rhytidectomy, and extended deep-plane rhytidectomy continuing the flap below the angle of the mandible into the neck with release of the platysma and cervical retaining ligaments., Results: The medial edge of the platysma muscle was distracted laterally 427% more with deep-plane rhytidectomy compared with SMAS-platysmal plication (P < .001). Extending the deep-plane rhytidectomy flap into the neck to release the cervical retaining ligaments resulted in 554% greater lateral distraction of the medial edge of the platysma muscle compared with SMAS-platysmal plication (P < .001). This represents 30% greater advancement compared with the traditional deep-plane technique (P = .05)., Conclusions: Extending a traditional deep-plane rhytidectomy inferiorly to release the lateral platysma and cervical retaining ligaments to the sternocleidomastoid muscle achieves the greatest lateral motion of the midline platysma, theoretically obviating the need for midline platysmal plication except in cases of severe platysmal laxity and banding. Because of the limited platysmal motion during SMAS plication, midline platysmal plication should routinely be used as an adjunct procedure except in cases of no or minimal platysmal laxity.

Transvenous pacemaker and/or defibrillator lead placement into the left heart chambers is rarely done. Approximately a third of such cases reported in the literature presented with signs of thromboembolism, mostly neurological deficits. We describe a patient who presented with a cerebrovascular accident three months after inadvertent and unrecognized lead placement into the left atrium and ventricle through a sinus venosus atrial septal defect. Implant techniques to avoid this complication are discussed.

Objective: To describe characteristics of older adults who received opioids for chronic non-cancer pain (CP), ascertain types of opioid treatments received, and examine associations between patient characteristics and treatment outcomes., Design: Retrospective cohort study., Setting: Primary care practice in New York City., Patients: Eligible patients were >or=65 and newly started on an opioid for CP., Outcome Measures: Patient characteristics and provider treatments, as well as duration of opioid therapy, proportion discontinuing therapy, and evidence of pain reduction and continued use of opioid for more than 1 year. Other outcomes included the presence and type(s) of side effects, abuse/misuse behaviors, and adverse events., Results: Participants (N = 133) had a mean age of 82 (range = 65-105), were mostly female (84%), and white (74%). Common indications for opioid treatment included back pain (37%) and osteoarthritis (35%). Mean duration of opioid use was 388 days (range = 0-1,880). Short-acting analgesics were most commonly prescribed. Physicians recorded side effects in 40% of cases. Opioids were discontinued in 48% of cases, mostly due to side effects/lack of efficacy. Pain reduction was documented in 66% of patient records, while 32% reported less pain and continued treatment for >or=1 year. Three percent displayed abuse/misuse behaviors, and 5% were hospitalized due to opioid-related adverse events., Conclusions: Over 50% of older patients with CP tolerated treatment. Treatment was discontinued in 48% of cases, mostly due to side effects and lack of analgesic efficacy. Efforts are needed to establish the long-term safety and efficacy of opioid treatment for CP in diverse older patient populations.

Background: Recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) has been well established and is in part related to left atrial (LA) size. The purpose of this study was to assess the predictive capability of LA diameter (LAD) and LA volume (LAV) by echocardiography and computed tomography (CT) to determine success in patients undergoing RFCA of AF., Methods: Eighty-eight patients with paroxysmal or persistent AF who had undergone RFCA and had a prior transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE), and CT were enrolled in the study. TTE LADs and LV ejection fraction as well as TEE LADs and LAVs in three views were recorded. CT LAVs were also recorded. Clinical parameters prior to ablation as well as at 1-year follow-up were assessed., Results: A total of 40 (45%) patients with paroxysmal AF and 48 (55%) patients with persistent AF were analyzed. Paroxysmal AF patients had a RFCA success rate of 88% at 1 year with persistent AF patients having a 52% success rate (P < 0.001). A CT-derived LAV >or= 117 cc was associated with an odds ratio (OR) for recurrence of 4.8 (95% confidence interval [CI]=[1.4-16.4], P = 0.01) while a LAV >or=130 cc was associated with an OR for recurrence of 22.0 (95% CI =[2.5-191.0], P = 0.005) after adjustment for persistent AF., Conclusions: LA dimensions and AF type are highly predictive of AF recurrence following RFCA. LAV by CT has significant predictive benefit over standard LADs in severely enlarged atria even after adjustment for AF type.

Background: Many implantable ventricular assist devices (VADs) have no direct measurement of pump output. The aim of this study was to test the hypothesis that quantitative contrast echocardiography can be used to measure VAD output., Methods: Contrast-enhanced Doppler velocity-time integral (VTI) was measured in the VAD inlet and outlet cannulae. Doppler flow (Doppler Q=Doppler VTIxcannula area) was compared with measured flow (Q). A total of 130 flow measurements were made (at 6400 and 12,000 rpm)., Results: Doppler Q in the outflow and inflow cannulae showed an excellent correlation with measured Q (outlet Doppler Q=1.0052 xQ+0.048, R2=0.9865; inlet Doppler Q=1.5043 xQ+0.003, R2=0.9904), but inlet Doppler Q was 50% higher. Correcting for the flow profile of the conical inlet tube yielded excellent correlation (inlet Doppler Q=1.0029 xQ+0.002, R2=0.9904)., Conclusion: Noninvasive Doppler flow techniques can be used to accurately measure VAD flow, but the flow profile in the cannula needs to be taken into account., (Copyright (c) 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: The advent of both high-resolution computed tomographic (CT) imaging and minimally invasive endoscopic techniques has led to revolutionary advances in sinus surgery. However, the rhinologist is left to make the conceptual jump between static cross-sectional images and the anatomy encountered intraoperatively. A three-dimensional (3D) visuo-haptic representation of the patient's anatomy may allow for enhanced preoperative planning and rehearsal, with the goal of improving outcomes, decreasing complications, and enhancing technical skills., Methods: We developed a novel method of automatically constructing 3D visuo-haptic models of patients' anatomy from preoperative CT scans for placement in a virtual surgical environment (VSE). State-of-the-art techniques were used to create a high-fidelity representation of salient bone and soft tissue anatomy and to enable manipulation of the virtual patient in a surgically meaningful manner. A modified haptic interface device drives a virtual endoscope that mimics the surgical configuration., Results: The creation and manipulation of sinus anatomy from CT data appeared to provide a relevant means of exploring patient-specific anatomy. Unlike more traditional methods of interacting with multiplanar imaging data, our VSE provides the potential for a more intuitive experience that can replicate the views and access expected at surgery. The inclusion of tactile (haptic) feedback provides an additional dimension of realism., Conclusion: The incorporation of patient-specific clinical CT data into a virtual surgical environment holds the potential to offer the surgeon a novel means to prepare for rhinologic procedures and offer training to residents. An automated pathway for segmentation, reconstruction, and an intuitive interface for manipulation may enable rehearsal of planned procedures.

Loss of the actin filament capping protein CapG has no apparent effect on the phenotype of mice maintained under sterile conditions; however, bone marrow-derived macrophages from CapG(-/-) mice exhibited distinct motility defects. We examined the ability of CapG(-/-) mice to clear two intracellular bacteria, Listeria monocytogenes and Salmonella enterica serovar Typhimurium. The 50% lethal dose of Listeria was 10-fold lower for CapG(-/-) mice than for CapG(+/+) mice (6 x 10(3) CFU for CapG(-/-) mice and 6 x 10(4) CFU for CapG(+/+) mice), while no difference was observed for Salmonella: The numbers of Listeria cells in the spleens and livers were significantly higher in CapG(-/-) mice than in CapG(+/+) mice at days 5 to 9, while the bacterial counts were identical on day 5 for Salmonella-infected mice. Microscopic analysis revealed qualitatively similar inflammatory responses in the spleens and livers of the two types of mice. Specific immunofluorescence staining analyzed by fluorescence-activated cell sorting revealed similar numbers of macrophages and dendritic cells in infected CapG(-/-) and CapG(+/+) spleens. However, analysis of bone marrow-derived macrophages revealed a 50% reduction in the rate of phagocytosis of Listeria in CapG(-/-) cells but a normal rate of phagocytosis of Salmonella: Stimulation of bone marrow-derived dendritic cells with granulocyte-macrophage colony-stimulating factor resulted in a reduction in the ruffling response of CapG(-/-) cells compared to the response of CapG(+/+) cells, and CapG(-/-) bone-marrowed derived neutrophils migrated at a mean speed that was nearly 50% lower than the mean speed of CapG(+/+) neutrophils. Our findings suggest that specific motility deficits in macrophages, dendritic cells, and neutrophils render CapG(-/-) mice more susceptible than CapG(+/+) mice to Listeria infection.

Background and Aims: Recent studies have reported high prevalence rates of short segments of specialized columnar epithelium (SCE) in the distal esophagus. The association of SCE with gastroesophageal reflux disease is not well established. We studied the prevalence and associations of short segments of SCE in the distal esophagus amongst Indians., Methods: 271 patients (mean age 36 [14] y; 160 men) undergoing diagnostic upper gastrointestinal endoscopy were interviewed regarding symptoms of gastroesophageal reflux, and history of medications, smoking or chewing tobacco and alcohol ingestion. At endoscopy, presence and grade of esophagitis and hiatus hernia were recorded. One biopsy each was taken from the squamocolumnar junction and 2 cm proximal to it. Biopsies were stained with hematoxylin/eosin and alcian blue/periodic acid-Schiff. The pathologist was blinded to the clinical and endoscopic data., Results: Short segments of SCE in the distal esophagus were present in 16/271 (6%; CI 5.03-6.97) patients. Increasing age (p<0.01), and endoscopic (p<0.01) and histologic (p<0.001) esophagitis were associated with its presence, whereas symptoms of gastroesophageal reflux, smoking, tobacco chewing, use of alcohol or non-steroidal anti-inflammatory drugs, and hiatus hernia were not. One patient with SCE had dysplasia., Conclusion: Prevalence of short segments of SCE in the distal esophagus amongst Indians is low and is usually associated with inflammation in the esophagus.

Cells have evolved distinct mechanisms for both preventing and removing mutagenic and lethal DNA damage. Structural and biochemical characterization of key enzymes that function in DNA repair pathways are illuminating the biological and chemical mechanisms that govern initial lesion detection, recognition, and excision repair of damaged DNA. These results are beginning to reveal a higher level of DNA repair coordination that ensures the faithful repair of damaged DNA. Enzyme-induced DNA distortions allow for the specific recognition of distinct extrahelical lesions, as well as tight binding to cleaved products, which has implications for the ordered transfer of unstable DNA repair intermediates between enzymes during base excision repair.

Uracil-DNA glycosylase (UDG) functions as a sentry guarding against uracil in DNA. UDG initiates DNA base excision repair (BER) by hydrolyzing the uracil base from the deoxyribose. As one of the best studied DNA glycosylases, a coherent and complete functional mechanism is emerging that combines structural and biochemical results. This functional mechanism addresses the detection of uracil bases within a vast excess of normal DNA, the features of the enzyme that drive catalysis, and coordination of UDG with later steps of BER while preventing the release of toxic intermediates. Many of the solutions that UDG has evolved to overcome the challenges of policing the genome are shared by other DNA glycosylases and DNA repair enzymes, and thus appear to be general.

Enzymatic transformations of macromolecular substrates such as DNA repair enzyme/DNA transformations are commonly interpreted primarily by active-site functional-group chemistry that ignores their extensive interfaces. Yet human uracil-DNA glycosylase (UDG), an archetypical enzyme that initiates DNA base-excision repair, efficiently excises the damaged base uracil resulting from cytosine deamination even when active-site functional groups are deleted by mutagenesis. The 1.8-A resolution substrate analogue and 2.0-A resolution cleaved product cocrystal structures of UDG bound to double-stranded DNA suggest enzyme-DNA substrate-binding energy from the macromolecular interface is funneled into catalytic power at the active site. The architecturally stabilized closing of UDG enforces distortions of the uracil and deoxyribose in the flipped-out nucleotide substrate that are relieved by glycosylic bond cleavage in the product complex. This experimentally defined substrate stereochemistry implies the enzyme alters the orientation of three orthogonal electron orbitals to favor electron transpositions for glycosylic bond cleavage. By revealing the coupling of this anomeric effect to a delocalization of the glycosylic bond electrons into the uracil aromatic system, this structurally implicated mechanism resolves apparent paradoxes concerning the transpositions of electrons among orthogonal orbitals and the retention of catalytic efficiency despite mutational removal of active-site functional groups. These UDG/DNA structures and their implied dissociative excision chemistry suggest biology favors a chemistry for base-excision repair initiation that optimizes pathway coordination by product binding to avoid the release of cytotoxic and mutagenic intermediates. Similar excision chemistry may apply to other biological reaction pathways requiring the coordination of complex multistep chemical transformations.

Objectives: The fregency of bacteremia after endoscopic variceal band ligation (EVL) is reported to be lower when compared to that after endoscopic variceal sclerotherapy (EVS). However, there are conflicting reports on the infectious sequelae after EVL., Aim: To compare the frequency on bacteremia and infectious sequelae after EVL and EVS in patients with cirrhosis of liver., Methods: Bacteremia and infectious sequelae were studied in 32 sessions of EVL in 18 cirrhotic patients (Child-Pugh class A-6, B-5, C-7), 30 sessions of EVS in 22 cirrhotic patients (Child-Pugh class A-2, B-5, C-15) and 14 diagnostic upper gastrointestinal endoscopies. Blood cultures were collected before, during and 30 minutes after the procedure. Patients were observed for infectious sequelae during subsequent hospitalization., Results: Before the procedure, bacteremia was present in 7/62 (11%) sessions. Significant bacteremia during and 30 min post-procedure developed in 8/32 (25%) and 12/30 (40%) of EVL and EVS sessions, respectively (p = ns), and in 1/14 (7%) upper gastrointestinal endoscopy sessions. There was more frequent bacteremia with severe liver disease (Child-Pugh class A-0/6, B-1/5. C-7/21; p = 0.09) in the EVL but not in the EVS group (Child-Pugh class A-1/3, B-2/5, C-9/22; p = ns). The incidence was higher with emergency sclerotherapy compared to elective sclerotherapy (6/8 [75%] vs 6/22 [27%]; p <0.01). One patient in the EVS group developed spontaneous bacterial peritonitis., Conclusions: Bacteremia occurs frequently following EVL and EVS in patients with advanced liver diseases. In the EVS group it is more common after emergency sclerotherapy. This bacteremia is rarely associated with significant infectious sequelae.

Recent breakthroughs integrate individual DNA repair enzyme structures, biochemistry and biology to outline the structural cell biology of the DNA base excision repair pathways that are essential to genome integrity. Thus, we are starting to envision how the actions, movements, steps, partners and timing of DNA repair enzymes, which together define their molecular choreography, are elegantly controlled by both the nature of the DNA damage and the structural chemistry of the participating enzymes and the DNA double helix.

Objective: Prostaglandins regulate gastric motor function. Inhibition of prostaglandins by nonsteroidal antiinflammatory drugs (NSAIDs) may alter gastric emptying. To study gastric emptying of solids and its relation to endoscopic findings and Helicobacter pylori in patients receiving long-term NSAIDs, we undertook this study., Methods: Ninety-five patients with arthritis, 65 taking long-term NSAIDs (Group I) and 30 not taking NSAIDs (Group II) were studied. Presence of dyspeptic symptoms was determined using a questionnaire. Mucosal damage was determined by endoscopy. H. pylori was detected by antral biopsies for rapid urease test and histology. Gastric emptying for solids was evaluated using a scintigraphic method. Thirty healthy volunteers were used as controls for gastric emptying (Group III). Patients with peptic ulcer were excluded from the analysis of gastric emptying. Logistic regression analysis was performed to identify predictive factors for gastric emptying., Results: Nineteen patients from Group I with peptic ulcers were excluded. Dyspeptic symptoms were seen in 24 (52%) Group I and seven (23%) Group II patients. Gastroduodenal erosions were seen in 10 (21.7%) Group I patients and four (13.3%) Group II patients. H. pylori was detected in 17 patients in Group I (36.9%) and Group II (56.6%). Gastric emptying was delayed in 24 (52%) Group I patients, six (20%) Group II patients (p < 0.001), and in none of the Group III controls. The mean gastric emptying times were 99.5 (15.6) min and 89 (17.7) min for Groups I and II, respectively (p < 0.05). Endoscopic damage was found with similar frequency in Group I patients with delayed or normal gastric emptying. H. pylori infection was present in 37.5% Group I patients with delayed gastric emptying and in 36.3% with normal gastric emptying (p = ns). Logistic regression analysis identified NSAID therapy as the single factor most predictive of delayed gastric emptying., Conclusion: Delayed gastric emptying was seen in 52% of patients on long-term NSAID therapy.

Recent structural and biochemical studies have begun to illuminate how cells solve the problems of recognizing and removing damaged DNA bases. Bases damaged by environmental, chemical, or enzymatic mechanisms must be efficiently found within a large excess of undamaged DNA. Structural studies suggest that a rapid damage-scanning mechanism probes for both conformational deviations and local deformability of the DNA base stack. At susceptible lesions, enzyme-induced conformational changes lead to direct interactions with specific damaged bases. The diverse array of damaged DNA bases are processed through a two-stage pathway in which damage-specific enzymes recognize and remove the base lesion, creating a common abasic site intermediate that is processed by damage-general repair enzymes to restore the correct DNA sequence.

The DNA glycosylase MutY, which is a member of the Helix-hairpin-Helix (HhH) DNA glycosylase superfamily, excises adenine from mispairs with 8-oxoguanine and guanine. High-resolution crystal structures of the MutY catalytic core (cMutY), the complex with bound adenine, and designed mutants reveal the basis for adenine specificity and glycosyl bond cleavage chemistry. The two cMutY helical domains form a positively-charged groove with the adenine-specific pocket at their interface. The Watson-Crick hydrogen bond partners of the bound adenine are substituted by protein atoms, confirming a nucleotide flipping mechanism, and supporting a specific DNA binding orientation by MutY and structurally related DNA glycosylases.

Three high-resolution crystal structures of DNA complexes with wild-type and mutant human uracil-DNA glycosylase (UDG), coupled kinetic characterizations and comparisons with the refined unbound UDG structure help resolve fundamental issues in the initiation of DNA base excision repair (BER): damage detection, nucleotide flipping versus extrahelical nucleotide capture, avoidance of apurinic/apyrimidinic (AP) site toxicity and coupling of damage-specific and damage-general BER steps. Structural and kinetic results suggest that UDG binds, kinks and compresses the DNA backbone with a 'Ser-Pro pinch' and scans the minor groove for damage. Concerted shifts in UDG simultaneously form the catalytically competent active site and induce further compression and kinking of the double-stranded DNA backbone only at uracil and AP sites, where these nucleotides can flip at the phosphate-sugar junction into a complementary specificity pocket. Unexpectedly, UDG binds to AP sites more tightly and more rapidly than to uracil-containing DNA, and thus may protect cells sterically from AP site toxicity. Furthermore, AP-endonuclease, which catalyzes the first damage-general step of BER, enhances UDG activity, most likely by inducing UDG release via shared minor groove contacts and flipped AP site binding. Thus, AP site binding may couple damage-specific and damage-general steps of BER without requiring direct protein-protein interactions.

Bilioma secondary to choledocholithiasis is rare. We report a patient in whom a large common bile duct stone was responsible for leak from the infraduodenal segment of the bile duct. Choledochotomy with extraction of stone followed by T-tube drainage of the bile duct and evacuation of the bilioma resulted in complete recovery.

DNA base excision repair (BER) is essential to preserving the integrity of the genome. Recent crystallographic studies of representatives from each enzyme class required for BER reveal clues to the structural basis of an entire DNA repair pathway.

We studied the seroprevalence of human immunodeficiency virus infection in patients with pulmonary tuberculosis and abdominal tuberculosis. We also assessed the clinical characteristics, risk factors, tuberculin status, site, and response to therapy of abdominal tuberculosis in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients. Volunteer blood donors (n = 8,395), patients with pulmonary tuberculosis (n = 387), and patients with abdominal tuberculosis (n = 108) were screened for HIV 1 and/or HIV 2 by enzyme-linked immunosorbent assay (ELISA; Torrent, India) and positivity reconfirmed by a repeat ELISA and Western blot test. The HIV seroprevalence in the abdominal tuberculosis patients (16.6%) was significantly higher compared with those with pulmonary tuberculosis (6.9%, p < 0.05) and volunteer blood donors (1.4%, p < 0.01). Absolute lymphocyte counts did not differ between the HIV-seropositive and HIV-seronegative patients (2,044.94 +/- 830 vs 2,261.34 +/- 805/mm3, p = NS). The Mantoux reaction was larger in the HIV-seronegative group as compared with the HIV-seropositive group (14.8 mm vs. 9.5 mm, p < 0.05). Tuberculosis patients responded well to conventional antituberculosis drugs in standard doses regardless of their HIV status.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are independent risk factors for gastroduodenal damage and peptic ulcer., Objective: To study the frequency and effect of H pylori infection on gastroduodenal mucosa in patients on long-term NSAID use., Methods: A total of 125 subjects were studied: 65 patients (Group 1) on NSAID therapy (> 6 months), 30 patients (Group 2) with arthritic disorders prior to starting NSAID therapy, and 30 healthy volunteers (Group 3). Dyspeptic symptoms were evaluated using a questionnaire. All patients underwent endoscopy and antral and duodenal biopsies were obtained to assess the extent of gastroduodenal damage and H pylori status., Results: H pylori infection was less frequent in Group 1 (37%) compared to Group 2 (57%, p = ns) and 3 (60%, p < 0.05). Among Group 1 patients, H pylori infection did not increase the risk of gastroduodenal damage (52% vs 45%) or ulceration (32% vs 27%). Group 1 patients with H pylori infection were more likely to be symptomatic (48% vs 27%) and have chronic active gastritis (76% vs 12%) and chronic active duodenitis (68% vs 5%). Gastric metaplasia was seen only in patients with H pylori infection, chronic active gastritis and duodenitis. Chemical gastritis was observed more commonly in Group 1 (34% vs 3%) compared to Group 2; its was not seen in Group 3. H pylori infection was less commonly observed in patients with chemical gastritis (8% vs 50%)., Conclusion: Patients on long-term NSAIDs are not at increased risk of H pylori infection. Presence H pylori infection is not associated with increased risk of gastroduodenal damage in these patients. H pylori infection correlated with presence of chronic active gastritis, and NSAID with presence of chemical gastritis.

Much interest has recently been focussed on the possibility of the involvement of unstable DNA in the etiology of schizophrenia and bipolar affective disorder (BPAD), following several publications that report increases in frequency of large CAG/CTG repeats in affected individuals. Using the Repeat Expansion Detection (RED) technique, we have performed a matched control pair analysis for both disorders. No significant differences in CAG/CTG repeat sizes were observed for 52 bipolar affecteds and matched controls (P = 0.15), and borderline significance was observed for 54 schizophrenia affecteds and matched controls (P = 0.05), using a (CTG)10 oligonucleotide (one-tailed t-tests for paired samples). Furthermore, using a (CTG)17 oligonucleotide, no significant differences were observed for 58 bipolar affecteds and 55 schizophrenia affecteds compared to 81 unmatched controls. No significant sex effect was observed for either group, and no significant differences in repeat size were found for responders and non-responders to drug treatments. More importantly, there was no significant correlation (either positive or negative) between age of onset of disease and size of repeat. We thus cannot conclude that CAG/CTG trinucleotides are involved in psychotic disorders and that either the differences observed in similar studies may be the result of population stratification, or that the increased frequency of larger repeats amongst affected individuals is a much smaller effect than previously thought.

Postoperative delirium is common in the elderly in the postoperative period. It can result in increased morbidity, delayed functional recovery, and prolonged hospital stay. In surgical patients, factors such as age, alcohol abuse, low baseline cognition, severe metabolic derangement, hypoxia, hypotension, and type of surgery appear to contribute to postoperative delirium. Anesthetics, notably anticholinergic drugs and benzodiazepines, increase the risk for delirium. Despite the above recommendations, postoperative delirium in the elderly is poorly understood. Clearly, further studies are needed to determine the risk and long-term outcome of delirium in the elderly population. Research is also needed to define the effects of hypoxemia on cerebral function and whether oxygen therapy has any benefits. The geriatric-anesthesiologic intervention program of pre- and postoperative geriatric assessment, early surgery, thrombosis prophylaxis, oxygen therapy, prevention and treatment of perioperative decrease in blood pressure, and vigorous treatment of any postoperative complications showed some promise, but further definitive studies are needed.