Long-Term Bonding Efficacy of CAD/CAM Hybrid Restorative Materials and Universal Adhesives.

OBJECTIVES: In-office and lab milled prostheses are the staple for indirect restorations. It is therefore critical to determine their long-term bonding durability. METHODS: CAD/ CAM blocks of two classes of restorative materials: 1) a nano-ceramic reinforced polymer matrix (NCPM) and, 2) a polymer-infiltrated ceramic network (PICN) were bonded using four different universal adhesives (UA) and silane systems. A lithium disilicate glassceramic (LDS) was used as a reference. The blocks were bisected and bonded with different UA/resin-cement pairs. Bonded blocks were then cut into 1.0x1.0x12.0 mm bar specimens for microtensile bond testing. Half the bars were subjected to bond strength testing immediately and the other half after aging by 50,000 thermal cycles between 5°C and 55°C. ANOVA and post-hoc tests were used to compare mean bond strength among groups. RESULTS: NCPM presented consistently high bond strength regardless of bonding techniques, while the bond strength of PICN and LDS were lower when bonded with UA relative to traditional silanes. The more hydrophilic UA produced higher bond strengths. DISCUSSION: Glass-ceramics exhibited lower bond strength with UA than the conventional etch-rinse-silane techniques. However, UAs preserved bonding interface in the long-term. SIGNIFICANCE: NCPM displayed superior bond strength relative to PICN and LDS regardless of the type of adhesives and bonding techniques.

Xanthan gum coatings augmented with lemongrass oil preserve postharvest quality and antioxidant defence system of Kinnow fruit under low-temperature storage.

Kinnow mandarin is an important citrus fruit that undergoes various postharvest qualitative losses. Therefore, the present study aimed to investigate the effect of polysaccharide-based xanthan gum (XG) coatings and lemongrass essential oil (LG) on the nutritive quality of Kinnow mandarins stored at 5-7 °C, 90-95 % RH for 75 days. The results revealed that in comparison to control the coatings maintained the fruit titratable acidity (TA), soluble solid content (SSC), ascorbic acid (AsA) content, total flavonoid content (TFC), and juice content, along with reduced weight loss and spoilage incidence. The coated fruits also exhibited higher sensory quality, total antioxidant activity (TAA), and activities of enzymes; catalase (CAT), peroxidase (POD), and phenylalanine ammonia-lyase (PAL). At the end of storage, the fruits coated with XG 1.0 % + LG 1.0 % exhibited maximum TA (0.69 %), AsA content (203.5 mg L-1), and TFC (0.21 mg g-1) with minimum weight loss (7.57 %) and spoilage (3.01 %) and SSC (11.87 %). The scanning electron microscopic (SEM) images of the coated fruits also exhibited smooth surfaces with closed stomata pores. Overall, XG 1.0 % + LG 1.0 % proved as a potential postharvest treatment for maintaining the nutritive quality of Kinnow under low-temperature storage.

Surgical Training Simulators for Rhinoplasty: A Systematic Review.

Rhinoplasty training currently follows an apprenticeship model that is largely observational. Trainees have limited experience in performing maneuvers of this complex surgery. Rhinoplasty simulators can address this issue by providing trainees with the opportunity to gain surgical simulator experience that could improve technical competences in the operating room. This review amalgamates the collective understanding of rhinoplasty simulators described to date. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, OVID Embase, OVID Medline, and Web of Science databases were all searched for original research on surgical simulators for rhinoplasty education and reviewed by independent reviewers. Articles underwent title and abstract screening, and then relevant articles underwent full-text review to extract simulator data. Seventeen studies, published between 1984 and 2021, were included for final analysis. Study participant numbers ranged from 4 to 24, and included staff surgeons, fellows, residents (postgraduate year 1-6), and medical students. Cadaveric surgical simulators comprised eight studies, of which three were with human cadavers, one study was a live animal simulator, two were virtual simulators, and six were three-dimensional (3D) models. Both animal and human-based simulators increased the confidence of trainees significantly. Significant improvement in various aspects of rhinoplasty knowledge occurred with implementation of a 3D-printed model in rhinoplasty education. Rhinoplasty simulators are limited by a lack of an automated method of evaluation and a large reliance on feedback from experienced rhinoplasty surgeons. Rhinoplasty simulators have the potential to provide trainees with the opportunity for hands-on training to improve skill and develop competencies without putting patients in harm's way. Current literature on rhinoplasty simulators largely focuses on simulator development, with few simulators being validated and assessed for utility. For wider implementation and acceptance, further refinement of simulators, validation, and assessment of outcomes is required.

Role of gum Arabic combined with cinnamic acid coating on quality and cell wall degradation enzymes of mango fruits at low temperature.

Mango exhibits a short shelf life when kept under ambient conditions. Therefore, this study was carried out to assess the synergistic effect of gum Arabic (GA) and cinnamic acid (CA) coatings on mango fruits stored for 28 days at 12 ± 1 °C. The treatments included GA 10 and 20 % sole and its formulation with CA 0.2 % while the uncoated fruits were used as control. The results revealed that GA + CA coatings exhibited reduced weight loss, flesh firmness, delayed respiratory peak, retained soluble solids content (SSC), titratable acidity (TA) and skin colour, retarded spoilage, and decreased electrolyte leakage of fruit as compared to uncoated fruit during storage. Among all, the coating GA 20 % + CA 0.2 % maintained higher firmness (16.6 N), SSC (20.1 %), TA (0.71 %), total flavonoid content (152 mg/kg) and total carotenoids content (45.1 mg/kg) and retained the higher sensory quality of mango fruit at the end of storage. Additionally, the GA 20 % + CA 0.2 % coating suppressed activities of polygalacturonase (PG), cellulase (CL) and pectin methyl esterase (PME) in stored mango fruits.

Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction.

High levels of lactate are positively associated with the prognosis and mortality in patients with heart attack. Endothelial-to-mesenchymal transition (EndoMT) plays an important role in cardiac fibrosis. Here, we report that lactate exerts a previously unknown function that increases cardiac fibrosis and exacerbates cardiac dysfunction by promoting EndoMT following myocardial infarction (MI). Treatment of endothelial cells with lactate disrupts endothelial cell function and induces mesenchymal-like function following hypoxia by activating the TGF-ß/Smad2 pathway. Mechanistically, lactate induces an association between CBP/p300 and Snail1, leading to lactylation of Snail1, a TGF-ß transcription factor, through lactate transporter monocarboxylate transporter (MCT)-dependent signaling. Inhibiting Snail1 diminishes lactate-induced EndoMT and TGF-ß/Smad2 activation after hypoxia/MI. The MCT inhibitor CHC mitigates lactate-induced EndoMT and Snail1 lactylation. Silence of MCT1 compromises lactate-promoted cardiac dysfunction and EndoMT after MI. We conclude that lactate acts as an important molecule that up-regulates cardiac EndoMT after MI via induction of Snail1 lactylation.

LACTATE IMPAIRS VASCULAR PERMEABILITY BY INHIBITING HSPA12B EXPRESSION VIA GPR81-DEPENDENT SIGNALING IN SEPSIS.

ABSTRACT: Introduction: Sepsis impaired vascular integrity results in multiple organ failure. Circulating lactate level is positively correlated with sepsis-induced mortality. We investigated whether lactate plays a role in causing endothelial barrier dysfunction in sepsis. Methods: Polymicrobial sepsis was induced in mice by cecal ligation and puncture (CLP). Lactic acid was injected i.p. (pH 6.8, 0.5 g/kg body weight) 6 h after CLP or sham surgery. To elucidate the role of heat shock protein A12B (HSPA12B), wild-type, HSPA12B-transgenic, and endothelial HSPA12B-deficient mice were subjected to CLP or sham surgery. To suppress lactate signaling, 3OBA (120 µM) was injected i.p. 3 h before surgery. Vascular permeability was evaluated with the Evans blue dye penetration assay. Results: We found that administration of lactate elevated CLP-induced vascular permeability. Vascular endothelial cadherin (VE-cadherin), claudin 5, and zonula occluden 1 (ZO-1) play a crucial role in the maintenance of endothelial cell junction and vascular integrity. Lactate administration significantly decreased VE-cadherin, claudin 5, and ZO-1 expression in the heart of septic mice. Our in vitro data showed that lactate (10 mM) treatment disrupted VE-cadherin, claudin 5, and ZO-1 in endothelial cells. Mechanistically, we observed that lactate promoted VE-cadherin endocytosis by reducing the expression of HSPA12B. Overexpression of HSPA12B prevented lactate-induced VE-cadherin disorganization. G protein-coupled receptor 81 (GPR81) is a specific receptor for lactate. Inhibition of GPR81 with its antagonist 3OBA attenuated vascular permeability and reversed HSPA12B expression in septic mice. Conclusions: The present study demonstrated a novel role of lactate in promoting vascular permeability by decreasing VE-cadherin junctions and tight junctions in endothelial cells. The deleterious effects of lactate in vascular hyperpermeability are mediated via HSPA12B- and GPR81-dependent signaling.

Composite coating of chitosan with salicylic acid retards pear fruit softening under cold and supermarket storage.

Fruit softening is enzyme mediated degradation process determined by the action of cell wall modifying enzymes. Present study evaluated the combined effects of chitosan (CH) and salicylic acid (SA) coatings in modulation of fruit softening enzymes in Punjab Beauty pear (Pyrus pyrifolia × Pyrus communis) fruit stored under cold (0-1 °C and 90-95 % RH) and supermarket (20-22 °C and 80-85 % RH) conditions. Composite CH + SA coatings reduced mass loss and retained fruit firmness throughout the 67 and 20 days storage period. In addition, CH + SA prevented membrane damage by suppressing the electrolyte leakage and malondialdehyde (MDA) accumulation as compared to CH or SA alone. CH 2.0 % + SA 2.0 mM coating efficiently delayed the cell wall degrading enzymatic activities including pectin methylesterase (PME), polygalacturonase (PG) and cellulase associated with fruit softening up to 60 and 15 days storage period in cold and supermarket conditions, respectively.

Trained Immunity Enhances Human Monocyte Function in Aging and Sepsis.

Aging plays a critical role in the incidence and severity of infection, with age emerging as an independent predictor of mortality in sepsis. Trained immunity reprograms immunocytes to respond more rapidly and effectively to pathogens and serves as a potential approach to improve immune function in aging and/or sepsis. However, there is very little data on trained immunity in the aging immune system or in the presence of sepsis. We examined the impact of ß-glucan induced innate immune training on monocytes from aging healthy humans (>60 years old) as well as sepsis patients. We observed increased metabolic capacity, upregulated cytokine secretion, increased H3K27 acetylation, and upregulation of crucial intracellular signaling pathways in trained monocytes from healthy aging subjects. The response to trained immunity in healthy aging monocytes was equivalent to the response of monocytes from younger, i.e., 18 - 59 years, individuals. Additionally, we found that trained immunity induced a unique expression pattern of cell surface markers in monocytes that was consistent across age groups. Trained monocytes from sepsis patients also displayed enhanced metabolic capacity and increased cytokine production. These results indicate that immune training can be induced in aging monocytes as well as monocytes from critically ill sepsis patients.

Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis.

Circulating lactate levels are a critical biomarker for sepsis and are positively correlated with sepsis-associated mortality. We investigated whether lactate plays a biological role in causing endothelial barrier dysfunction in sepsis. We showed that lactate causes vascular permeability and worsens organ dysfunction in CLP sepsis. Mechanistically, lactate induces ERK-dependent activation of calpain1/2 for VE-cadherin proteolytic cleavage, leading to the enhanced endocytosis of VE-cadherin in endothelial cells. In addition, we found that ERK2 interacts with VE-cadherin and stabilizes VE-cadherin complex in resting endothelial cells. Lactate-induced ERK2 phosphorylation promotes ERK2 disassociation from VE-cadherin. In vivo suppression of lactate production or genetic depletion of lactate receptor GPR81 mitigates vascular permeability and multiple organ injury and improves survival outcome in polymicrobial sepsis. Our study reveals that metabolic cross-talk between glycolysis-derived lactate and the endothelium plays a critical role in the pathophysiology of sepsis.

Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis.

High circulating levels of lactate and high mobility group box-1 (HMGB1) are associated with the severity and mortality of sepsis. However, it is unclear whether lactate could promote HMGB1 release during sepsis. The present study demonstrated a novel role of lactate in HMGB1 lactylation and acetylation in macrophages during polymicrobial sepsis. We found that macrophages can uptake extracellular lactate via monocarboxylate transporters (MCTs) to promote HMGB1 lactylation via a p300/CBP-dependent mechanism. We also observed that lactate stimulates HMGB1 acetylation by Hippo/YAP-mediated suppression of deacetylase SIRT1 and ß-arrestin2-mediated recruitment of acetylases p300/CBP to the nucleus via G protein-coupled receptor 81 (GPR81). The lactylated/acetylated HMGB1 is released from macrophages via exosome secretion which increases endothelium permeability. In vivo reduction of lactate production and/or inhibition of GPR81-mediated signaling decreases circulating exosomal HMGB1 levels and improves survival outcome in polymicrobial sepsis. Our results provide the basis for targeting lactate/lactate-associated signaling to combat sepsis.

Diagnosis of osteoarticular tuberculosis by immuno-PCR assay based on mycobacterial antigen 85 complex detection.

Diagnosis of osteoarticular tuberculosis (OATB) exhibits serious challenges owing to paucibacillary nature of specimens and localization of disease at sites that are difficult to access. We recently developed indirect immuno-PCR (I-PCR) and real-time I-PCR (RT-I-PCR) assays for the detection of mycobacterial antigen 85 complex (Ag85) in OATB patients. Detection limits for the purified Ag85 protein were found to be 1 and 41 fg ml-1 by I-PCR and RT-I-PCR, respectively, which were at least 105 -fold lower than respective ELISA. While spiking synovial fluids of non-TB control subjects with the purified Ag85 protein, LODs of 100 and 120 fg ml-1 were obtained by I-PCR and RT-I-PCR, respectively, thus demonstrating the sample matrix effect. Sensitivities of 87·5 and 70·5% were observed in bodily fluids of confirmed (n = 8) and clinically suspected (n = 51) OATB cases, respectively, by I-PCR, with a specificity of 93·9% (n = 33). Markedly, the sensitivities obtained by I-PCR/RT-I-PCR were significantly higher (P < 0·05-0·01) than ELISA and GeneXpert assay (n = 30). However, no substantial difference in sensitivity was observed between the I-PCR and RT-I-PCR assays. After further improving the accuracy of I-PCR, this test may lead to development of an attractive diagnostic kit.

Mistaking a Tumour for an Infection - Acrometastasis of the Finger from Endocervical Adenosquamous Carcinoma: A Case Report.

Acrometastasis is rare with a very low incidence of all bone metastasis. It can present with swelling, pain and warmth with erythema that may mimic an infection especially in the distal phalanx. Due to its rarity and subtle clinical presentation, it can be misdiagnosed as an infection causing the treatment to be delayed. We report a 42-year-old female with an acrometastasis to the distal phalanx of the left middle finger which we mistook as an infection thus delaying her treatment. It was a terminal presentation of her endocervical adenosquamous carcinoma. We would like to highlight that acrometastasis has an indistinct presentation and in cases where the lesion does not respond to treatment, acrometastasis should be included as one of the differential diagnoses. Thus, physicians need to have a high level of suspicion in patients with a primary malignant tumour.

The patient perspective, experience and satisfaction of day case unicompartmental knee arthroplasty: A short-term mixed-methods study.

BACKGROUND: Day case unicompartmental knee arthroplasty (UKA) is increasingly being performed worldwide. When performed in the appropriate patient, day case UKA has been demonstrated to be safe, cost effective and improve resource allocation. Limited evidence highlights increased patient satisfaction of day case UKA when compared with inpatient UKA. A detailed study of the patient perspective, experience and satisfaction following day case UKA has not been described before. METHODS: A retrospective case series review of 21 consecutive patients (19 unilateral, 2 bilateral) undergoing day case UKA in an elective orthopaedic centre was undertaken. A qualitative and quantitative patient assessment of the day case UKA experience was administered. A five-point Likert scale satisfaction questionnaire, Oxford Knee Score (OKS) and open-ended interview was undertaken. The qualitative responses underwent thematic analysis. RESULTS: One hundred percent of patients expressed satisfaction (76.2% completely satisfied, 33.8% moderately satisfied) with day case UKA. The majority of patients (90.5%) reported that if they had to undergo UKA again they would prefer a day case over an inpatient procedure. Patients consider surgical outcome, physiotherapy provision, discharge planning, postoperative medications and follow up as key aspects of day case UKA care. One patient was re-admitted following discharge. CONCLUSIONS: The present study demonstrates a high level of patient satisfaction with day case UKA. The results reported herein are subject to the study limitations of sample size, recall bias and inclusion criteria. We recommend that the themes identified by patients are addressed through a multidisciplinary approach with well-defined clinical pathways for a high-quality patient-centred experience.

Efficacy of postharvest sodium nitroprusside application to extend storability by regulating physico-chemical quality of pear fruit.

Quality loss in pear fruit during storage reduces its marketability for long run. To increase its storability, the efficacy of postharvest dip treatment donor sodium nitroprusside (SNP) 0.000, 0.001, 0.002 and 0.003 mol L-1 were investigated on pear fruit cv. Patharnakh under storage conditions (low temperature 0-1 °C and relative humidity (90-95%). SNP effectively lowered fruit mass loss, retained colour and higher firmness, suppressed browning and respiration rate and sustained soluble solids content, titratable acidity, total phenol content and ascorbic acid thus conserved the fruit quality for longer period. SNP treatments suppressed the activity of polyphenol oxidase and increased activity of superoxide dismutase enzyme. Additionally, the SNP treated fruit exhibited lesser activities of fruit softening enzymes like pectin methylesterase, polygalacturonase and cellulase. Among all, 0.002 mol L-1 SNP concentration was superior to lengthen storability and sensory quality of pear up to 60 d under cold storage.

Understanding the holistic experiences of living with a kidney transplant: an interpretative phenomenological study (protocol).

BACKGROUND: Currently very little is known about the perceptions and experiences of kidney transplant recipients from a qualitative perspective. As highlighted by the European Kidney Health Alliance recommendations, providing holistic care to kidney patients is important however this is currently an unmet care need in renal disease. It is imperative to understand patient experiences to ensure that they are included in key strategies and future renal service planning. Ignoring these important patient views means that there is a significant risk of inappropriate renal service provision and lack of adequate support impacting on overall health. METHOD: A purposive sampling strategy will recruit individuals currently living with a kidney transplant, 6 months to 5 years post-transplant. A maximum of 30 patients will be recruited between two Regional Nephrology units within the United Kingdom via clinical gatekeepers. In-depth interviews will be undertaken with participants living with a kidney transplant across the two sites. Interviews will be digitally-recorded, transcribed verbatim and subjected to interpretative phenomenological analysis. DISCUSSION: Renal healthcare professionals need to understand more than the biological impact of receiving a kidney transplant. Understanding the holistic and multi-domain experiences that these patients experience will help healthcare professionals to recognize the needs of this group and ensure more responsive care.

Novel Role of Endothelial Derived Exosomal HSPA12B in Regulating Macrophage Inflammatory Responses in Polymicrobial Sepsis.

Endothelial cell dysfunction contributes to sepsis induced initiate immune response and the infiltration of immune cells into organs, resulting in organ injury. Heat shock protein A12B (HSPA12B) is predominantly expressed in endothelial cells. The present study investigated whether endothelial HSPA12B could regulate macrophage pro-inflammatory response during sepsis. Wild type (WT) and endothelial cell-specific HSPA12B deficient (HSPA12B-/-) mice were subjected to CLP sepsis. Mortality and cardiac function were monitored. Higher mortality, worsened cardiac dysfunction, and greater infiltrated macrophages in the myocardium and spleen were observed in HSPA12B-/- septic mice compared with the WT septic mice. The serum levels of TNF-α and IL-1ß were higher and the levels of IL-10 were lower in HSPA12B-/- septic mice than in WT septic mice. Importantly, endothelial exosomes contain HSPA12B which can be uptaken by macrophages. Interestingly, endothelial exosomal HSPA12B significantly increases IL-10 levels and decreases TNF-α and IL-1ß production in LPS-stimulated macrophages. Mechanistic studies show that endothelial exosomal HSPA12B downregulates NF-κB activation and nuclear translocation in LPS stimulated macrophages. These data suggest that endothelial HSPA12B plays a novel role in the regulation of macrophage pro-inflammatory response via exosomes during sepsis and that sepsis induced cardiomyopathy and mortality are associated with endothelial cell deficiency of HSPA12B.

Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Sex differences in the association of risk factors for heart failure incidence and mortality.

BACKGROUND: There are known risk factors associated with the development of heart failure (HF), but it is not fully understood whether these differ by sex. OBJECTIVES: To investigate sex differences in risk factors for HF incidence and mortality. METHODS: 468 941 participants (55.9% women, age range 37-73 years) were included. Established CVD risk factors (hypertension, hypercholesterolaemia, diabetes type 1 and 2, adiposity, smoking, physical activity and poor diet) and novel risk factors (grip strength, fitness, TV viewing and sleep duration) were the exposures of interest. HF incidence and mortality were the outcomes. RESULTS: Over a mean follow-up of 9.0 years, 1812 participants developed HF and 763 died due to HF. Women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), hypertension, hypercholesterolaemia, low levels of physical activity and fitness, low strength, high levels of TV viewing, sleep duration <7 hours/day, smokers; those who were underweight and who were obese, had high body surface area and those who drink >14 units of alcohol were at higher risk of HF incidence. However, in women T2DM, hypercholesterolaemia, >3 hours/day of TV and sleep <7 hours/day, low level of physical activity and high level of TV viewing were more strongly associated with HF incidence compared with men. CONCLUSION: Several modifiable risk factors (in particular diabetes) appear more strongly associated with HF in women compared with men. The relevance of these findings to HF characteristics and future outcomes needs to be established.

Medical Malpractice Defense: The Predictive and Protective Power of Mortality, Survival, and Life Expectancy.

Introduction.-The defense of medical malpractice presents a significant challenge to Assistant United States Attorneys (AUSAs). A medical malpractice claim consists of proof of: (1) duty, (2) breach of the duty, (3) causation, and (4) damages. Often the breach of the duty and the causation elements present complex medical issues involving multiple specialties and subspecialties of medicine. A considerable amount of time is required to prepare the defense pertaining to the alleged breach of the duty and causation elements. The damages aspect of the medical malpractice case is often not given equal treatment and may not be fully developed. As a result, damage awards can be surprisingly high once the breach of the standard of care and the causation defenses fail. Purpose.-The purpose of this article is to underscore the importance of developing the damages aspect of the case. This article will demonstrate through a case study the power of using fact-based medical-actuarial risk statistics and life expectancy testimony to limit, by thousands if not millions of dollars, economic damages to impairment-specific "years of life lost" in medical-malpractice torts. The important points to remember are that from the moment a case is assigned to an AUSA, the AUSA must: (1) focus as much, if not more, attention on damages; (2) execute a discovery strategy that ensures all aspects of damages are thoroughly investigated; and (3) retain the appropriate experts, including, in appropriate cases, an expert on medical risk appraisal and life expectancy.