Amyloid Accelerator Polyphosphate Implicated as the Mystery Density in α-Synuclein Fibrils.

Aberrant aggregation of α-Synuclein is the pathological hallmark of a set of neurodegenerative diseases termed synucleinopathies. Recent advances in cryo-electron microscopy have led to the structural determination of the first synucleinopathy-derived α-Synuclein fibrils, which contain a non-proteinaceous, "mystery density" at the core of the protofilaments, hypothesized to be highly negatively charged. Guided by previous studies that demonstrated that polyphosphate (polyP), a universally conserved polyanion, significantly accelerates α-Synuclein fibril formation, we conducted blind docking and molecular dynamics simulation experiments to model the polyP binding site in α-Synuclein fibrils. Here we demonstrate that our models uniformly place polyP into the lysine-rich pocket, which coordinates the mystery density in patient-derived fibrils. Subsequent in vitro studies and experiments in cells revealed that substitution of the two critical lysine residues K43 and K45 leads to a loss of all previously reported effects of polyP binding on α-Synuclein, including stimulation of fibril formation, change in filament conformation and stability as well as alleviation of cytotoxicity. In summary, our study demonstrates that polyP fits the unknown electron density present in in vivo α-Synuclein fibrils and suggests that polyP exerts its functions by neutralizing charge repulsion between neighboring lysine residues.

A Survey to Assess the Current Status of Structured Benefit-Risk Assessment in the Global Drug and Medical Device Industry.

BACKGROUND: This industry survey was conducted to gain insight into the ways structured Benefit-Risk assessment (sBRA) of medical products is approached across drug or medical device developing companies, including frameworks and methods that are currently used and areas where future work is being planned. METHODS: A survey containing 28 questions covering five key areas of sBRA was set-up and shared with representatives from the participating companies. Each company was asked to complete a single survey response including inputs across the company's multidisciplinary key representatives involved in benefit-risk assessment. RESULTS: Of the 26 participating companies, 21 (81%) are conducting sBRA. Considering these 21 qualitative frameworks were used by almost every company (19, 90%), while only 12 (57%) have used a quantitative method. Many companies have sBRA training (17, 81%), document templates (16,76%), Standard Operating Procedures (SOPs)/checklists (13, 62%), and /or best practice manuals/examples (12,57%) available. Considering all 26 companies Software tools (15, 58%) and BR planning documents (11,42%) were identified as areas into which many companies intend to put effort. CONCLUSIONS: The industry survey confirmed a wide usage of sBRA by many companies involved in research and development. Nevertheless, sBRA is evolving and several future opportunities like the implementation of visualization tools were identified by the representatives of the pharmaceutical companies. Finally, challenges like the cross-functional comprehension of the added value of sBRA are still seen.

Phosphorylations and Acetylations of Cytochrome c Control Mitochondrial Respiration, Mitochondrial Membrane Potential, Energy, ROS, and Apoptosis.

Cytochrome c (Cytc) has both life-sustaining and cellular death-related functions, depending on subcellular localization. Within mitochondria, Cytc acts as a single electron carrier as part of the electron transport chain (ETC). When released into the cytosol after cellular insult, Cytc triggers the assembly of the apoptosome, committing the cell to intrinsic apoptosis. Due to these dual natures, Cytc requires strong regulation by the cell, including post-translational modifications, such as phosphorylation and acetylation. Six phosphorylation sites and three acetylation sites have been detected on Cytc in vivo. Phosphorylations at T28, S47, Y48, T49, T58, and Y97 tend to be present under basal conditions in a tissue-specific manner. In contrast, the acetylations at K8, K39, and K53 tend to be present in specific pathophysiological conditions. All of the phosphorylation sites and two of the three acetylation sites partially inhibit respiration, which we propose serves to maintain an optimal, intermediate mitochondrial membrane potential (ΔΨm) to minimize reactive oxygen species (ROS) production. Cytc phosphorylations are lost during ischemia, which drives ETC hyperactivity and ΔΨm hyperpolarization, resulting in exponential ROS production thus causing reperfusion injury following ischemia. One of the acetylation sites, K39, shows a unique behavior in that it is gained during ischemia, stimulating respiration while blocking apoptosis, demonstrating that skeletal muscle, which is particularly resilient to ischemia-reperfusion injury compared to other organs, possesses a different metabolic strategy to handle ischemic stress. The regulation of Cytc by these post-translational modifications underscores the importance of Cytc for the ETC, ΔΨm, ROS production, apoptosis, and the cell as a whole.

Diffractive optical computing in free space.

Structured optical materials create new computing paradigms using photons, with transformative impact on various fields, including machine learning, computer vision, imaging, telecommunications, and sensing. This Perspective sheds light on the potential of free-space optical systems based on engineered surfaces for advancing optical computing. Manipulating light in unprecedented ways, emerging structured surfaces enable all-optical implementation of various mathematical functions and machine learning tasks. Diffractive networks, in particular, bring deep-learning principles into the design and operation of free-space optical systems to create new functionalities. Metasurfaces consisting of deeply subwavelength units are achieving exotic optical responses that provide independent control over different properties of light and can bring major advances in computational throughput and data-transfer bandwidth of free-space optical processors. Unlike integrated photonics-based optoelectronic systems that demand preprocessed inputs, free-space optical processors have direct access to all the optical degrees of freedom that carry information about an input scene/object without needing digital recovery or preprocessing of information. To realize the full potential of free-space optical computing architectures, diffractive surfaces and metasurfaces need to advance symbiotically and co-evolve in their designs, 3D fabrication/integration, cascadability, and computing accuracy to serve the needs of next-generation machine vision, computational imaging, mathematical computing, and telecommunication technologies.

Distinct microbial communities degrade cellulose diacetate bioplastics in the coastal ocean.

IMPORTANCE: Cellulose diacetate (CDA) is a promising alternative to conventional plastics due to its versatility in manufacturing and low environmental persistence. Previously, our group demonstrated that CDA is susceptible to biodegradation in the ocean on timescales of months. In this study, we report the composition of microorganisms driving CDA degradation in the coastal ocean. We found that the coastal ocean harbors distinct bacterial taxa implicated in CDA degradation and these taxa have not been previously identified in prior CDA degradation studies, indicating an unexplored diversity of CDA-degrading bacteria in the ocean. Moreover, the shape of the plastic article (e.g., a fabric, film, or foam) and plasticizer in the plastic matrix selected for different microbial communities. Our findings pave the way for future studies to identify the specific species and enzymes that drive CDA degradation in the marine environment, ultimately yielding a more predictive understanding of CDA biodegradation across space and time.

Factors Affecting Anxiety-Related Symptoms, Diagnosis, and Treatment Among Collegiate Student-Athletes in the National College Health Assessment.

CONTEXT: Increased attention continues to be placed on best practices for assisting student-athletes who show symptoms of a mental health illness. One of the most common mental health concerns for student-athletes is feeling overwhelmed or anxious. Early recognition of these symptoms can help student-athletes find early intervention. OBJECTIVE: To elucidate specific attributes associated with an increased likelihood of anxiety symptoms and treatment avoidance to help athletic trainers and other practitioners better identify and assist high-risk individuals. DESIGN: Cross-sectional study. SETTING: Colleges and universities in the United States. PATIENTS OR OTHER PARTICIPANTS: A total of 51 882 varsity athletes who completed the National College Health Assessment between 2011 and 2019. MAIN OUTCOME MEASURE(S): Survey responses (self-report) to questions related to anxiety symptoms and disorders cross-sectioned into 9 predictors: year in school, gender, sexual orientation, race and ethnicity, international student status, school type, received information on stress reduction or depression or anxiety, anxiety about impeding academic performance, and history of mental health treatment in the last year. RESULTS: More than three-fourths (82.9%, n = 43 016) of student-athletes reported feeling overwhelmed because of all that they had to do in their daily activities, whereas only half (47.5%, n = 24 645) of student-athletes described overwhelming anxiety as a symptom. Gender, sexual orientation, race and ethnicity, school type, and previous mental health treatment had large effects on these 2 symptoms. However, of the student-athletes who reported overwhelming anxiety as a symptom, only one-fourth (22.9%, n = 5649) indicated they received a diagnosis of anxiety with or without treatment. CONCLUSIONS: Factors such as the year in school and availability of mental health information appeared to have little effect on the experience of anxiety-related symptoms and the propensity to seek treatment. However, other factors, including gender, sexual orientation, race and ethnicity, school type, and previous mental health treatment, did have important effects. Our study provides additional evidence that the stresses placed on collegiate student-athletes frequently led to feelings of being overwhelmed and, eventually, anxiety disorder diagnoses. However, most student-athletes experiencing anxiety-related symptoms still did not seek a diagnosis with or without treatment.

Molecular Processes Leading to Shear Banding in Entangled Polymeric Solutions.

The temporal and spatial evolution of shear banding during startup and steady-state shear flow was studied for solutions of entangled, linear, monodisperse polyethylene C3000H6002 dissolved in hexadecane and benzene solvents. A high-fidelity coarse-grained dissipative particle dynamics method was developed and evaluated based on previous NEMD simulations of similar solutions. The polymeric contribution to shear stress exhibited a monotonically increasing flow curve with a broad stress plateau at intermediate shear rates. For startup shear flow, transient shear banding was observed at applied shear rates within the steady-state shear stress plateau. Shear bands were generated at strain values where the first normal stress difference exhibited a maximum, with lifetimes persisting for up to several hundred strain units. During the lifetime of the shear bands, an inhomogeneous concentration distribution was evident within the system, with higher polymer concentration in the slow bands at low effective shear rate; i.e., γ˙<τR-1, and vice versa at high shear rate. At low values of applied shear rate, a reverse flow phenomenon was observed in the hexadecane solution, which resulted from elastic recoil of the molecules within the slow band. In all cases, the shear bands dissipated at high strains and the system attained steady-state behavior, with a uniform, linear velocity profile across the simulation cell and a homogeneous concentration.

Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle.

Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochrome c oxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 Å) and acetylmimetic K39Q Cytc (1.36 Å) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury.

Trends in Collegiate Student-Athlete Mental Health in the National College Health Assessment, 2011-2019.

CONTEXT: Recently, the athletic training community has paid increased attention to collegiate student-athlete mental health, mental health treatment-seeking behavior, and the effects of mental health factors on athletic and academic performance. Ongoing efforts to better educate and equip athletic trainers to help student-athletes in this regard should result in improved mental health-related outcomes. OBJECTIVE: To examine changes in the mental health of student-athletes over the past decade compared with that of nonathlete students. DESIGN: Cross-sectional study. SETTING: Colleges and universities in the United States. PATIENTS OR OTHER PARTICIPANTS: Varsity athletes (athletes; n = 54 479) and nonathlete students (nonathletes; n = 448 301) who completed the National College Health Assessment between 2011 and 2019. MAIN OUTCOME MEASURE(S): Surveys included responses (self-reported) to questions in 5 mental health-related categories: recent mental health symptoms, recent mental health diagnosis, mental health treatment-seeking behavior, receiving mental health information from the institution, and the recent effect of mental health factors on academic performance. RESULTS: Athletes consistently described lower symptom and diagnosis rates compared with nonathletes, except for attempted suicide, substance abuse, and eating disorders. Rates of diagnosis increased over time in both groups but remained lower in athletes. Treatment-seeking behavior and openness to future treatment increased over time in both groups but remained lower in athletes. Athletes received more information on stress reduction, substance abuse, eating disorders, and handling distress or violence compared with nonathletes. Both groups received information more frequently over time. Athletes reported fewer academic effects, especially for depression and anxiety, but these effects grew over time in both groups. The effects of injuries and extracurricular activities on academic performance were greater in athletes than in nonathletes. CONCLUSIONS: Athletes described overall lower levels of mental health symptoms, diagnoses, and academic effects compared with nonathletes. Whereas the rates in nonathletes climbed over the past decade, the rates in athletes broadly remained flat or climbed less rapidly. Increasingly positive attitudes toward treatment were encouraging, but the deficit in athletes relative to nonathletes persisted. Ongoing efforts of athletic trainers to educate athletes and guide them to mental health resources are needed to continue, or better yet to accelerate, the observed positive trends in information dissemination and treatment-seeking behavior.

Atomistic Simulation of Flow-Induced Microphase Separation and Crystallization of an Entangled Polyethylene Melt Undergoing Uniaxial Elongational Flow and the Role of Kuhn Segment Extension.

Atomistic simulations of the linear, entangled polyethylene C1000H2002 melt undergoing steady-state and startup conditions of uniaxial elongational flow (UEF) over a wide range of flow strength were performed using a united-atom model for the atomic interactions between the methylene groups constituting the polymer macromolecules. Rheological, topological, and microstructural properties of these nonequilibrium viscoelastic materials were computed as functions of strain rate, focusing on regions of flow strength where flow-induced phase separation and flow-induced crystallization were evident. Results of the UEF simulations were compared with those of prior simulations of planar elongational flow, which revealed that uniaxial and planar flows exhibited essentially a universal behavior, although over strain rate ranges that were not completely equivalent. At intermediate flow strength, a purely configurational microphase separation was evident that manifested as a bicontinuous phase composed of regions of highly stretched molecules that enmeshed spheroidal domains of relatively coiled chains. At high flow strength, a flow-induced crystallization (FIC) occurred, producing a semicrystalline material possessing a high degree of crystallinity and primarily a monoclinic lattice structure. This FIC phase formed at a temperature (450 K) high above the quiescent melting point (≈400 K) and remained stable after cessation of flow for temperature at or below 435 K. Careful examination of the Kuhn segments constituting the polymer chains revealed that the FIC phase only formed once the Kuhn segments had become essentially fully extended under the UEF flow field. Thermodynamic properties such as the heat of fusion and heat capacity were estimated from the simulations and found to compare favorably with experimental values.

Abnormal enteric nervous system and motor activity in the ganglionic proximal bowel of Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a congenital defect in which the enteric nervous system (ENS) does not develop in the distal bowel, requiring surgical removal of the portions of bowel without ENS ganglia ('aganglionic') and reattachment of the 'normal' proximal bowel with ENS ganglia. Unfortunately, many HSCR patients have persistent dysmotility (e.g., constipation, incontinence) and enterocolitis after surgery, suggesting that the remaining bowel is not normal despite having ENS ganglia. Anatomical and neurochemical alterations have been observed in the ENS-innervated proximal bowel from HSCR patients and mice, but no studies have recorded ENS activity to define the circuit mechanisms underlying post-surgical HSCR dysfunction. Here, we generated a HSCR mouse model with a genetically-encoded calcium indicator to map the ENS connectome in the proximal colon. We identified abnormal spontaneous and synaptic ENS activity in proximal colons from GCaMP-Ednrb -/- mice with HSCR that corresponded to motor dysfunction. Many HSCR-associated defects were also observed in GCaMP-Ednrb +/- mice, despite complete ENS innervation. Results suggest that functional abnormalities in the ENS-innervated bowel contribute to post-surgical bowel complications in HSCR patients, and HSCR-related mutations that do not cause aganglionosis may cause chronic colon dysfunction in patients without a HSCR diagnosis.

Solving integral equations in free space with inverse-designed ultrathin optical metagratings.

As standard microelectronic technology approaches fundamental limitations in speed and power consumption, novel computing strategies are strongly needed. Analogue optical computing enables the processing of large amounts of data at a negligible energy cost and high speeds. Based on these principles, ultrathin optical metasurfaces have been recently explored to process large images in real time, in particular for edge detection. By incorporating feedback, it has also recently been shown that metamaterials can be tailored to solve complex mathematical problems in the analogue domain, although these efforts have so far been limited to guided-wave systems and bulky set-ups. Here, we present an ultrathin Si metasurface-based platform for analogue computing that is able to solve Fredholm integral equations of the second kind using free-space visible radiation. A Si-based metagrating was inverse-designed to implement the scattering matrix synthesizing a prescribed kernel corresponding to the mathematical problem of interest. Next, a semitransparent mirror was incorporated into the sample to provide adequate feedback and thus perform the required Neumann series, solving the corresponding equation in the analogue domain at the speed of light. Visible wavelength operation enables a highly compact, ultrathin device that can be interrogated from free space, implying high processing speeds and the possibility of on-chip integration.

Effects of pubertal growth variation on knee mechanics during walking in female and male adolescents.

INTRODUCTION: Puberty substantially alters the body's mechanical properties, neuromuscular control, and sex differences therein, likely contributing to increased, sex-biased knee injury risk during adolescence. Female adolescents have higher risk for knee injuries than male adolescents of similar age engaging in similar physical activities, and much research has investigated sex differences in mechanical risk factors. However, few studies address the considerable variation in pubertal growth (timing, pace), knee mechanics, and injury susceptibility within sexes, or the impact of such growth variation on mechanical injury risk. OBJECTIVES: The present study tested for effects of variation in pubertal growth on established mechanical knee injury risk factors, examining relationships between and within sexes. METHODS: Pubertal growth indices describing variation in the timing and rate of pubertal growth were developed using principal component analysis and auxological data from serial stature measurements. Linear mixed models were applied to evaluate relationships between these indices and knee mechanics during walking in a sample of adolescents. RESULTS: Later developing female adolescents with slower pubertal growth had higher extension moments throughout stance, whereas earlier developers had higher valgus knee angles and moments. In male adolescents, faster and later growth were related to higher extension moments throughout gait. In both sexes, faster growers had higher internal rotation moments at foot-strike. CONCLUSIONS: Pubertal growth variation has important effects on mechanical knee injury risk in adolescence, affecting females and males differently. Earlier developing females exhibit greater injury risk via frontal plane factors, whereas later/faster developing males have elevated risk via sagittal plane mechanisms.

Microstructural evolution and reverse flow in shear-banding of entangled polymer melts.

The temporal and spatial evolution of shear banding under startup of shear flow was simulated for highly entangled, linear, monodisperse polyethylene melts of differing molecular weight, C750H1502, C1200H2402, and C3000H6002, using a high-fidelity coarse-grained dissipative particle dynamics method. It was determined that shear stress was dominated by segmental orientation of entangled strands at low shear rates, but at a critical shear rate below the reciprocal of the Rouse time, flow-induced disentanglement resulted in the onset of chain tumbling that reduced the average degree of orientation, leading to a regime of decreasing shear stress, with a commensurate onset of increasing average chain extension imposed by the strong flow kinematics that ultimately drove the steady-state shear stress higher. During startup of shear flow, shear band development began immediately after the maximum in the first normal stress difference, where distinct fast and slow bands formed. The slow bands consisted of relatively entangled and coiled molecules, whereas the fast bands consisted of more disentangled and extended chains that experienced quasiperiodic rotation/retraction cycles. The simulation results often exhibited a generation of temporary reverse flow, in which the local fluid velocity was temporarily opposite to that of the bulk flow direction, at the onset of the shear-banding phenomena; this effect was consistent with earlier experiments and theoretical results. The physical mechanism for the generation of reverse flow during shear-band formation was investigated and found to be related to the recoil of the molecules comprising the slow band. Overall, the phenomenon of shear banding appeared to arise due to flow-induced disentanglement from orientational ordering and segmental stretching that affected individual chains to different degrees, ultimately resulting in regions of relatively coiled and entangled chains that evolved into a slow band, whereas the locally disentangled chains, experiencing quasiperiodic stretch-rotation cycles, formed a fast band. The transitional period resulted in a kinematic instability that generated the temporary reverse-flow phenomenon.

Examining the incidence of reporting mental health diagnosis between college student athletes and non-athlete students and the impact on academic performance.

Objective: Compare collegiate athletes to non-athlete students for mental health diagnosis, treatment, and mental health impacts on academic performance. Participants: Students, including club and varsity athletes, from a large Midwestern U.S. NCAA Division 1 university (N = 2167). Methods: American College Health Association (ACHA)-NCHA II (2010-2016) survey data were analyzed using chi square tests for between-groups differences and gender effects on mental health diagnoses, treatment, and academic impacts of mental health. Results: Compared to athletes, non-athletes reported higher rates of anxiety, eating, mood, sleep, and other disorders. Controlling for gender, these differences were not significant. Regardless of gender, athletes sought treatment less often than non-athletes. Athletes reported anxiety, sleep, alcohol/drugs, extracurricular activities and injuries as major academic impediments. Conclusions: Mental health diagnosis rates were lower in athletes, but appeared to be an artifact of gender differences between groups. However, less treatment-seeking and academic impacts mean that ongoing attention to mental health is vital to student-athlete well-being.

Terbinafine-Induced Liver Injury: A Case Report.

Hepatic injuries attributable to terbinafine usage are a well-documented yet infrequent phenomenon. This case study details the clinical presentation and management of a 70-year-old Hispanic female, with no previous medical history, subsequently hospitalized for progressive jaundice, right upper quadrant abdominal discomfort, and worsening pruritus. A comprehensive review of her prior records revealed a recent terbinafine prescription for onychomycosis, which she took consistently for five weeks and then self-discontinued four weeks before her current admission. Laboratory tests on admission revealed a cholestatic pattern of liver injury, evident by transaminitis and conjugated hyperbilirubinemia. The R factor used to determine whether a liver injury is hepatocellular or cholestatic was 0.9. Further diagnostic imaging, including abdominal ultrasound, CT of the abdomen, and magnetic resonance cholangiopancreatography, failed to disclose an obstructive pathology, revealing only cholelithiasis and chronic cholecystitis. Therapeutically, the patient was initiated on hydroxyzine to address symptoms of pruritus, and then subsequently underwent a liver biopsy. Histopathologic findings from the biopsy revealed benign hepatic parenchyma demonstrating focal canalicular cholestasis, mild chronic inflammation involving select portal tracts, and chronic lobular inflammation, suggesting terbinafine-induced hepatotoxicity. This case highlights the challenges of diagnosing terbinafine-induced liver injury, emphasizing the need for a high index of clinical suspicion and recognizing the potential for prolonged symptomatic manifestation after drug discontinuation. This article provides valuable insights into the complexities inherent in such diagnoses and significantly enriches a medical provider's approach to diagnosing and treating unexplained liver injuries.

Structural analysis and functional evaluation of the disordered ß-hexosyltransferase region from Hamamotoa (Sporobolomyces) singularis.

Hamamotoa (Sporobolomyces) singularis codes for an industrially important membrane bound ß-hexosyltransferase (BHT), (BglA, UniprotKB: Q564N5) that has applications in the production of natural fibers such as galacto-oligosaccharides (GOS) and natural sugars found in human milk. When heterologously expressed by Komagataella phaffii GS115, BHT is found both membrane bound and soluble secreted into the culture medium. In silico structural predictions and crystal structures support a glycosylated homodimeric enzyme and the presence of an intrinsically disordered region (IDR) with membrane binding potential within its novel N-terminal region (1-110 amino acids). Additional in silico analysis showed that the IDR may not be essential for stable homodimerization. Thus, we performed progressive deletion analyses targeting segments within the suspected disordered region, to determine the N-terminal disorder region's impact on the ratio of membrane-bound to secreted soluble enzyme and its contribution to enzyme activity. The ratio of the soluble secreted to membrane-bound enzyme shifted from 40% to 53% after the disordered N-terminal region was completely removed, while the specific activity was unaffected. Furthermore, functional analysis of each glycosylation site found within the C-terminal domain revealed reduced total secreted protein activity by 58%-97% in both the presence and absence of the IDR, indicating that glycosylation at all four locations is required by the host for the secretion of active enzyme and independent of the removed disordered N-terminal region. Overall, the data provides evidence that the disordered region only partially influences the secretion and membrane localization of BHT.

A Rare Case of Phentermine-Induced Nonischemic Cardiomyopathy.

Obesity is a global epidemic with steadily increasing prevalence in most countries. Weight loss is generally challenging for patients to tackle in the face of the temptation to overeat and avoid physical activity. Hence, clinicians and patients alike are likely to steer toward the use of anorexigens. We report the case of a 33-year-old female with no significant cardiac history who presented with dyspnea, productive cough, and chest pressure for one month and was diagnosed with new-onset heart failure with a reduced ejection fraction secondary to prolonged phentermine use. The authors aim to highlight phentermine's potential for precipitating heart failure, even in a young, relatively healthy person, especially with a growing obese population. Ultimately, healthy weight loss can be achieved by implementing dietary changes and encouraging adequate physical activity, as the World Health Organization (WHO) recommended. Anorectic drugs may be employed for short-term use. Further research concerning the long-term side effects of phentermine may avert the prescriber and patient from abusing this drug.