Characterization of Outcomes of 2-Stage Exchange Arthroplasty in the Treatment of Prosthetic Joint Infections.

BACKGROUND: Two-stage revision is the preferred treatment for prosthetic hip and knee infections in the United States. Recent studies have questioned the true success rate of this treatment. The purpose of this study is to investigate outcomes of prosthetic hip and knee infections undergoing resection arthroplasty and spacer insertion at a single institution. METHODS: We identified 103 patients who underwent prosthesis resection and spacer placement for infection over a 10-year period. Twenty-three cases were excluded based on preset exclusion criteria leaving 80 cases (56 knees, 24 hips). A retrospective review was performed to examine the outcomes of these patients. RESULTS: Following spacer placement but before reimplantation, 9 (11.25%) of the 80 joints underwent repeat debridement and spacer exchange for persistent infection. Twenty-four (30.00%) patients had a serious complication during their treatment course. Fourteen (17.50%) patients never underwent reimplantation. Of these, 10 continued with spacer retention, 2 had resection arthroplasty, and 1 each had an amputation and an arthrodesis. Of the 66 patients with successful reimplantation, 48 (72.70%) remained infection free at most recent follow-up. CONCLUSIONS: Two-stage revision does not result in the high rates of cure reported previously, when taking into account the substantial number of patients who never undergo the subsequent reimplantation surgery. Of those who underwent reimplantation in our study, many required additional spacer exchange or had complications. Surgeons and patients should consider these outcomes when discussing the treatment of prosthetic hip and knee infections.

The feasibility and promise of mobile technology with community health worker reinforcement to reduce rural preterm birth.

OBJECTIVES: (1) Assess feasibility of a smartphone platform intervention combined with Community Health Worker (CHW) reinforcement in rural pregnant women; (2) Obtain data on the promise of the intervention on birth outcomes, patient activation, and medical care adherence; and (3) Explore financial implications of the intervention using return on investment (ROI). SAMPLE: A total of 98 rural pregnant women were enrolled and assigned to intervention or control groups in this two-group experimental design. INTERVENTION: The intervention group received usual prenatal care plus a smartphone preloaded with a tailored prenatal platform with automated texting, chat function, and hyperlinks and weekly contact from the CHW. The control group received usual prenatal care and printed educational materials. MEASUREMENTS: Demographics, health risk data, interaction with platform, medical records, hospital billing charges, Client Satisfaction Questionnaire-8, satisfaction comments, and the Patient Activation Measure. RESULTS: A total of 77 women completed the study. The intervention was well-received, showed promise for improving birth outcomes, patient activation, and medical care adherence. Financial analysis showed a positive ROI under two scenarios. CONCLUSIONS: Despite several practical issues, the study appears feasible. The intervention shows promise for extending prenatal care and improving birth outcomes in rural communities. Further research is needed with a larger and more at-risk population to appreciate the impact of the intervention.

Identification of populations at risk: Stillbirth toolkit for health care providers.

BACKGROUND: Maternity care and women's health are measured, in part, by the stillbirth rate of a country. The purposes of this pilot project were to: a) establish a baseline of health care provider knowledge regarding stillbirth risk factors based on geographic distribution (urban/rural) and provider licensure (MD, APRN, PA, CNM) and b) evaluate the utility of a Stillbirth Risk Factor Toolkit and its effects on provider knowledge. METHODS: Evaluative research using a retrospective pre-posttest survey design was completed. The study setting included primary care clinics (urban [n=25] and rural [n=25]) in Nebraska. Health care providers from N=50 clinics were surveyed about their knowledge of stillbirth risk factors (modifiable and non-modifiable) before and after reading the Toolkit. RESULTS: Providers were least knowledgeable regarding the definition of stillbirth and the number of weeks' gestation that constitute a stillbirth. Overall, there was no significant difference in baseline knowledge between rural and urban providers. Nearly half (43.8%) found the Toolkit to be very helpful and applicable to their patient population, and 34.8% said they would be very likely to utilize it with their patients. There was a statistically significant increase in knowledge of stillbirth risk factors among all health care providers after reviewing the Toolkit (p<0.001). CONCLUSIONS: Health providers had varied baseline knowledge about stillbirth. The Toolkit improved provider knowledge, but further research is needed to assess its impact on clinical practice.

An Integrative Review of Postpartum Depression in Rural U.S. Communities.

AIM: This study's aim is to synthesize and summarize the literature on postpartum depression (PPD) in U.S. rural populations. BACKGROUND: Internationally, PPD has a high prevalence in rural communities. Although women in rural U.S. communities have higher rates of depression outside of the postpartum time period, little study has been conducted on PPD in U.S. rural populations. It is unknown whether rural women in the United States have high rates of PPD as is common in rural populations internationally. DESIGN: We used integrative literature review using Whittemore and Knafl's (2005) methodology. DATA SOURCES AND METHODS: We searched the databases MEDLINE, CINAHL, PsycINFO, and Academic Search Premier with the words "postpartum depression" or "postnatal depression" and the word "rural." RESULTS: We found 11 articles with empirical data that met the criteria and thus were included in the review. Seven articles were quantitative, two were qualitative, one was mixed methods, and one was a nonexperimental design. Five foci emerged in the literature including (a) screening and prevalence, (b) demographic factors, (c) program creation and implementation, (d) mental health care seeking, and (e) social support. The results suggest that prevalence of PPD may be higher in rural U.S. areas, that implementing PPD prevention and screening programs for rural women is feasible, and that women in rural areas rely on informal networks and may face a stigma for seeking mental health care. CONCLUSIONS: Further research is needed on PPD in rural U.S. POPULATIONS: Specifically, this research should focus on the mix of variables found throughout this review such as race and income level. Nurses should lead for changes in clinical practice and policy that increase screening and interventions for PPD in rural communities.

Accountability for reasonableness: the relevance, or not, of exceptionality in resource allocation.

Accountability for Reasonableness has gained international acceptance as a framework to assist with resource allocation within healthcare. Despite this, one of the four conditions, the relevance condition, has not been widely adopted. In this paper I will start by examining the relevance condition, and the constraints placed on it by Daniels and Sabin. Following this, I review the theoretical limitations of the condition identified to date, by prominent critics such as Rid, Friedman, Lauridsen and Lippert-Rasmussen. Finally, I respond to Daniels and Sabin's enthusiasm for testing the accountability for reasonableness framework in different contexts, by evaluating the challenges of implementing the relevance condition within the NHS. I use the funding of treatments for patients on the basis of their exceptional circumstances as a case study to examine whether the relevance condition could be applied in practice.

Efficacy of acamprosate for alcohol dependence in a family medicine setting in the United States: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Acamprosate has been found to enhance rates of complete abstinence and to increase percent days abstinent (PDA) from alcohol relative to placebo treatment. As most U.S. clinical trials of acamprosate have been conducted in alcohol and other drug specialty clinics, there is a need to examine the efficacy of acamprosate in generalist settings. This study tested the efficacy of acamprosate versus placebo on the primary study outcome of PDA in the treatment of alcohol-dependent patients in a family medicine setting. Secondary study outcomes included percent heavy drinking days (%HDD) and gamma glutamyltransferase level (normal or high). METHODS: A randomized, double-blind, placebo-controlled, parallel group design of acamprosate was conducted in 2 family medicine settings (North Carolina and Wisconsin). One hundred volunteers were recruited primarily by advertisement, and participants were assigned to 666 mg (2 pills) oral acamprosate 3 times daily (1,998 mg/d) or matching placebo over a 12-week period. All participants concomitantly received 5 sessions of a brief behavioral intervention from a family/primary care physician. RESULTS: No significant treatment effect of acamprosate was found on PDA or the secondary outcomes. Significant treatment goal by time interaction effects was found on PDA and %HDD. Participants who had an initial goal of abstinence versus a reduction in alcohol use improved on average over time in PDA and had less %HDD from baseline to the end of treatment. CONCLUSIONS: This clinical trial did not find evidence of efficacy for acamprosate compared to placebo among alcohol-dependent individuals recruited primarily by advertisement as studied in a primary care setting. Drinking outcomes significantly improved regardless of medication condition. A goal of abstinence was significantly associated with improved drinking outcomes, suggesting that alcohol-dependent patients with such a goal may do particularly well with counseling in a family medicine setting.

Application of particle swarm optimization to understand the mechanism of action of allosteric inhibitors of the enzyme HSD17ß13.

Understanding a drug candidate's mechanism of action is crucial for its further development. However, kinetic schemes are often complex and multi-parametric, especially for proteins in oligomerization equilibria. Here, we demonstrate the use of particle swarm optimization (PSO) as a method to select between different sets of parameters that are too far apart in the parameter space to be found by conventional approaches. PSO is based upon the swarming of birds: each bird in the flock assesses multiple landing spots while at the same time sharing that information with its neighbors. We applied this approach to the kinetics of HSD17ß13 enzyme inhibitors, which displayed unusually large thermal shifts. Thermal shift data for HSD17ß13 indicated that the inhibitor shifted the oligomerization equilibrium toward the dimeric state. Validation of the PSO approach was provided by experimental mass photometry data. These results encourage further exploration of multi-parameter optimization algorithms as tools in drug discovery.

A study of symptoms described by ovarian cancer survivors.

OBJECTIVE: A cross-sectional, observational study to evaluate physical and psychological symptoms experienced by patients following completion of treatment for ovarian cancer and compared to symptoms documented in their hospital notes. METHODS: Women attending follow-up clinic at Hammersmith Hospital having undergone treatment for primary or relapsed ovarian cancer were asked to complete two validated questionnaires (EORTC QLQ-C30 and QLQ-OV28) and a "wellbeing thermometer". Results were assessed and stratified by patient age, tumour stage, relapse status, type of chemotherapy received and treatment-free interval. Symptoms reported in questionnaires were compared to those documented in patients' hospital notes. RESULTS: Of 116 women approached, 100 (86%) participated in this study and had received chemotherapy for ovarian cancer between 2003 and 2010. The most frequently described and severe symptoms reported in the questionnaires were emotional symptoms, negative feelings about treatment or prognosis, fatigue and pain. Dyspareunia, cognitive impairment and peripheral neuropathy were also frequently described. Symptom severity was independent of variables such as disease stage, type of chemotherapy received and relapse status. The "wellbeing thermometer" scores closely correlated with pain, fatigue, weakness, gastrointestinal symptoms and attitude to disease or treatment (p<0.001). There was a marked discordance between questionnaire-reported symptoms and those recorded in hospital notes. CONCLUSIONS: The majority of women surveyed experienced persistent psychological and physical symptoms following ovarian cancer treatment; in particular: psychological concerns, sexual inactivity and fatigue, all potentially reversible with appropriate interventions. Our results highlight the extent of symptoms described by ovarian cancer survivors and the need for them to be adequately acknowledged and addressed.

The concept of exceptionality: a legal farce?

How do we decide which treatments should be offered by the National Health Service (NHS) when we cannot afford to fund them all? In the absence of a positive appraisal by the National Institute for Health and Clinical Excellence (NICE), which mandates the provision of a treatment by the NHS, Primary Care Trusts (PCTs) are free to decide whether to provide a particular drug to some, or all, of their population. However, as public bodies, it is a well-established principle of Administrative Law that PCTs are not at liberty to fetter the exercise of their own discretion. They must recognise the possibility that some patients will have exceptional circumstances, and as a consequence, any general policy prohibiting the funding of a drug cannot be absolute. In the absence of statutory guidance on what might constitute exceptional, clinicians are left guessing as to whether their patients might be eligible for funding on the grounds of exceptionality. Using the context of expensive cancer drugs, I will examine the concept of exceptionality from clinical, moral, and legal perspectives, focussing particularly on the role of social factors in determining exceptionality. I will review the cases where PCTs' decisions not to fund cancer drugs were subject to legal action and argue that the courts have provided little guidance on interpreting the term exceptional, and that the concept has a limited role to play in the allocation of scarce health resources at a local level.

Client Retention in Community Treatment: Completer and Noncompleter Experiences of an Individualized, Needs-Based Partner Abuse Intervention Program.

There has been increased interest in the subjective experiences of participants of community partner abuse intervention programs (PAIPs). In the context of high attrition rates, qualitative research is needed to understand the factors associated with sustained engagement and dropout. Using a community nonmandated PAIP, the current study is a rare investigation of the experiences of both completers and noncompleters. We explored the differences between completers' and noncompleters' perceptions of the treatment process, the reasons for sustained program engagement, and the perceived outcomes of treatment. Semi-structured interviews were completed with 14 participants: nine completers and five noncompleters. The majority of participants were referred by children's social care and were unemployed at the time of interview. The interviews were conducted by research staff independent from the treatment-providing organization. Three themes emerged from the data: (a) Treatment as Challenging Yet Enlightening, (b) the Importance of a Well-timed and Safe Therapeutic Environment, and (c) Improved Emotional Self-Management Due to Treatment. Results highlighted how structured individualized sessions, underpinned by a strong therapeutic alliance with facilitators, helped participants increase their interpersonal problem-solving and communication skills. The study reinforced the importance of developing a therapeutic alliance and providing structured individualized treatment characterized by flexibility and accessibility. Noncompletion was perceived as related to known risk factors and treatment readiness. Therefore, it may be beneficial to employ screening measures to monitor these factors. Future research should use larger, more diverse samples to further investigate subjective experiences of PAIP completers and, particularly, noncompleters to enhance the limited literature in this area.

Quantifying Radiation Exposure From Intraoperative Computed Tomography in Traditionally Safe Operating Room Zones.

OBJECTIVES: To quantify the amount of radiation exposure from a commercially available computed tomography surgical imaging system that occurs in areas of the operating room that are generally believed to be safe and to correlate these amounts with established safety recommendations. DESIGN: Experimental in vitro study. SETTING: Standard hospital operating room at a Level 1 trauma center. PARTICIPANTS: Radiation survey instruments at specified distances from an intraoperative computed tomography scanner. Represented positions were the location of the anesthesiologist (80 cm), the radiation technologist (180 cm), the substerile room (500 cm), the operating room door (600 cm), the next-room nursing station (960 cm), and the hallway (1000 cm). INTERVENTION: Radiation survey instruments were systematically exposed by a protocol intended to imitate expected radiation scatter during operative room use. MAIN OUTCOME MEASUREMENTS: Radiation exposure readings from radiation survey instruments. RESULTS: The mean radiation exposure rates are reported. The mean exposure rate was highest at the anesthesiologist (2200 mrem/h), followed by the door (25.33 mrem/h), the technologist (21.0 mrem/h), the substerile room (8.2 mrem/h), the hallway (2.633 mrem/h), and then the next-room nursing station (1.557 mrem/h). The mean integrated doses per scan were 15.03 mrem for the anesthesiologist, 0.170 mrem for the technologist, 0.136 mrem at the door, 0.033 mrem in the substerile room, 0.014 mrem in the hallway, and 0.005 mrem at the next-door nursing station. The exposure was related both to distance from the machine and to orientation from the machine. CONCLUSIONS: These results indicate that although there is measurable radiation exposure outside of the operating room, the magnitude is low enough to be clinically insignificant. This study provides data that reinforce the need to wear a protective gear or leave the room during the use of intraoperative computed tomography but unsuspecting surrounding staff need not worry about uninformed exposure.

Management of Periprosthetic Hip and Knee Joint Infections With a Known Sinus Tract-A Single-Center Experience.

BACKGROUND: Prosthetic joint infection (PJI) is a serious complication after total joint arthroplasty (TJA). A sinus tract communicating with a prosthetic joint is a major criterion defining PJI. Despite this fact, many patients presenting with a draining sinus tract undergo invasive procedures before initiation of two-stage revision arthroplasty. We hypothesized that many patients undergo nondefinitive procedures to treat the sinus tract, rather than undergoing definitive treatment of infection with two-stage revision. METHODS: A retrospective review of all cases of two-stage revision arthroplasty at Loyola University Medical Center between January 2004 and May 2018 was performed. Patients with infected TJA and periprosthetic sinus tract were included. Records were queried for laboratory values and prior procedures. RESULTS: We identified 160 patients who underwent two-stage revision for infection over the 14-year period. Of the 160 patients, 25 had a documented periprosthetic sinus tract before initiation of definitive revision arthroplasty and were included. Eleven (44.0%) had one or more procedures including interventional radiology drain placement, local wound care, or formal irrigation and debridement before definitive treatment. Forty-five percent of patients that underwent nondefinitive procedures before definitive surgery had either an erythrocyte sedimentation rate or C-reactive protein at normal or near-normal levels. CONCLUSION: Many arthroplasty patients presenting with periprosthetic sinus tracts undergo nondefinitive procedures before definitive treatment. Inherent surgical risks of these procedures can increase the overall morbidity and mortality of these patients. Further effort is needed to educate surgeons regarding management of sinus tracts after TJA.

Clinical and Radiographic Predictors of Nonunion in Open Tibial Shaft Fractures.

Open fracture is a risk factor for nonunion of diaphyseal tibia fractures. Compared with closed injuries, there is a relative lack of scientific knowledge regarding the healing of open tibia fractures. The objective of this study was to investigate which patient, injury, and surgeon-related factors predict nonunion in open tibial shaft fractures. A cohort of 98 patients with 104 extra-articular open tibial shaft fractures (OTA/AO 41A2-3, 42A-C, and 43A) were treated surgically between 2007 and 2018 at a single level 1 trauma center and were retrospectively reviewed. Patients underwent irrigation and debridement followed by definitive intramedullary nailing or plate fixation. Patient, injury, and perioperative prognostic factors were analyzed as predictors of nonunion based on anteroposterior and lateral radiographs. The nonunion rate was 27.9% (n=29). There were 12 occurrences of deep infection (11.5%). The median follow-up was 14 months. High-energy mechanism of injury (hazard ratio [HR], 5.76), Gustilo-Anderson class IIIA injury (HR, 3.66), postoperative cortical continuity of 0% to 25% (HR, 2.90), early postoperative complication (HR, 4.20), and deep infection (HR, 2.25) were significant predictors of nonunion on univariable analysis (P<.05). On multivariable assessment, only high-energy mechanism of injury, Gustilo-Anderson class IIIA injury, and early postoperative complication reached significance as predictors of nonunion. These data also indicate that lack of cortical continuity is a significant univariable radiographic predictor of nonunion. This is potentially modifiable, may guide surgeons in selecting patients for early bone grafting procedures, and should be assessed carefully in this high-risk population. [Orthopedics. 2021;44(3):142-147.].

Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer.

Increased breakdown of glucose through glycolysis in both aerobic and anaerobic conditions is a hallmark feature of mammalian cancer and leads to increased production of L-lactate. The high-level lactate present within the tumor microenvironment is reused as a crucial biofuel to support rapid cancer cell proliferation, survival, and immune evasion. Inhibitors that target the glycolysis process are being developed for cancer therapy. In this study, we report an approach of using synthetic D-lactate dimers to inhibit melanoma and squamous cell carcinoma cell proliferation and survival. We also provide in vivo evidence that intratumoral injection of D-lactate dimers induced an innate immune response and inhibited subcutaneous melanoma xenograft growth in immunodeficient mice. Our findings support a potential utility of D-lactate dimers in skin cancer treatment and therefore warrant further mechanistic studies.

Gelation or molecular recognition; is the bis-(α,ß-dihydroxy ester)s motif an omnigelator?

Understanding the gelation of liquids by low molecular weight solutes at low concentrations gives an insight into many molecular recognition phenomena and also offers a simple route to modifying the physical properties of the liquid. Bis-(α,ß-dihydroxy ester)s are shown here to gel thermoreversibly a wide range of solvents, raising interesting questions as to the mechanism of gelation. At gelator concentrations of 5-50 mg ml⁻¹, gels were successfully formed in acetone, ethanol/water mixtures, toluene, cyclohexane and chloroform (the latter, albeit at a higher gelator concentration). A range of neutron techniques - in particular small-angle neutron scattering (SANS) - have been employed to probe the structure of a selection of these gels. The universality of gelation in a range of solvent types suggests the gelation mechanism is a feature of the bis-(α,ß-dihydroxy ester) motif, with SANS demonstrating the presence of regular structures in the 30-40 Å range. A correlation between the apparent rodlike character of the structures formed and the polarity of the solvent is evident. Preliminary spin-echo neutron scattering studies (SESANS) indicated the absence of any larger scale structures. Inelastic neutron spectroscopy (INS) studies demonstrated that the solvent is largely unaffected by gelation, but does reveal insights into the thermal history of the samples. Further neutron studies of this kind (particularly SESANS and INS) are warranted, and it is hoped that this work will stimulate others to pursue this line of research.

The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer.

The c-Jun N-terminal kinases (JNKs), with its members JNK1, JNK2, and JNK3, is a subfamily of (MAPK) mitogen-activated protein kinases. JNK signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apoptosis, and inflammation. Dysregulation of JNK pathway is associated with a wide range of immune disorders and cancer. Our objective is to provide a review of JNK proteins and their upstream regulators and downstream effector molecules in common skin disorders, including psoriasis, dermal fibrosis, scleroderma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

Mood and anxiety disorders in females with the FMR1 premutation.

Fragile X syndrome (FXS) is a model for studying the relative contributions of genetic and environmental factors to psychiatric disorders in mothers of children with disabilities. Here, we examine the frequency and predictors of mood and anxiety disorders in mothers with the FMR1 premutation. Ninety-three females with the FMR1 premutation were in the study and were compared to 2,159 women from the National Comorbidity Survey Replication (NCS-R) dataset. Mood and anxiety disorders were assessed using the SCID-I. Our data reflect elevated lifetime major depressive disorder (MDD), lifetime panic disorder without agoraphobia and current agoraphobia without panic disorder in the FMR1 premutation sample. Also, we found a low frequency of lifetime social phobia, specific phobia, and post-traumatic stress disorders and current specific phobia in the FMR1 premutation sample. The profile of MDD in the FMR1 premutation sample was not episodic or comorbid with an anxiety disorder, as in the NCS-R dataset. Never having been married and smaller CGG repeat length were associated with increased likelihood of MDD while increased children with FXS in the family and greater child problem behaviors were associated with increased likelihood of an anxiety disorder in the FMR 1 premutation group. Major depression in females with the FMR1 premutation may not be characterized as an episodically chronic recurrent disorder as it is in community samples and may have a genetic basis given the relationship with CGG repeat length and lack of association with all child and most demographic factors.

Sulfhydryl Labeling as a Tool to Investigate the Topology of Membrane Proteins Involved in Lipopolysaccharide Biosynthesis.

Establishing the topology of membrane proteins, especially when their tridimensional structures are unavailable, is critical to identify functional regions, delimit the protein orientation in the membrane, the number of transmembrane segments, and the position of critical amino acids (whether exposed to the solvent or embedded in the lipid bilayer). Elucidating the topology of bacterial integral membrane proteins typically involves the construction of deletion-fusions whereby regions of the protein are fused to reporters. Although these methods have several advantages, they are also artifact prone. In contrast, methods based on single amino acid substitutions preserve the native protein intact. We describe here an assay to analyze the topology of membrane proteins involved in the biogenesis of bacterial glycoconjugates, which is based on the accessibility of cysteine substitutions at various places in the protein under in vivo and in vitro conditions. Cysteine residues are detected with polyethylene glycol-maleimide (PEG-Mal). This procedure can be applied to crude bacterial cell extracts and does not require protein purification.

Thiol stress-dependent aggregation of the glycolytic enzyme triose phosphate isomerase in yeast and human cells.

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants, and xenobiotics. Cysteine-containing proteins are especially at risk, as the thiol side chain is subject to oxidation, adduction, and chelation by thiol-reactive compounds. The thiol-chelating heavy metal cadmium is a highly toxic environmental pollutant demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of cadmium toxicity responsible for these outcomes are largely unknown. Using fluorescent protein fusion to cytosolic proteins with known redox-active cysteines, we identified the yeast glycolytic enzyme triose phosphate isomerase as being aggregation-prone in response to cadmium and to glucose depletion in chronologically aging cultures. Cadmium-induced aggregation was limited to newly synthesized Tpi1 that was recruited to foci containing the disaggregase Hsp104 and the peroxiredoxin chaperone Tsa1. Misfolding of nascent Tpi1 in response to both cadmium and glucose-depletion stress required both cysteines, implying that thiol status in this protein directly influences folding. We also demonstrate that cadmium proteotoxicity is conserved between yeast and human cells, as HEK293 and HCT116 cell lines exhibit recruitment of the protein chaperone Hsp70 to visible foci. Moreover, human TPI, mutations in which cause a glycolytic deficiency syndrome, also forms aggregates in response to cadmium treatment, suggesting that this conserved enzyme is folding-labile and may be a useful endogenous model for investigating thiol-specific proteotoxicity.