The systems biology simulation core library.

SUMMARY: Studying biological systems generally relies on computational modeling and simulation, e.g., model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED-ML) or the Open Modeling EXchange format. Conducting simulation experiments based on these formats requires efficient and reusable implementations to make them accessible to the broader scientific community and to ensure the reproducibility of the results. The Systems Biology Simulation Core Library (SBSCL) provides interpreters and solvers for these standards as a versatile open-source API in JavaTM. The library simulates even complex bio-models and supports deterministic Ordinary Differential Equations; Stochastic Differential Equations; constraint-based analyses; recent SBML and SED-ML versions; exchange of results, and visualization of in silico experiments; open modeling exchange formats (COMBINE archives); hierarchically structured models; and compatibility with standard testing systems, including the Systems Biology Test Suite and published models from the BioModels and BiGG databases. AVAILABILITY AND IMPLEMENTATION: SBSCL is freely available at https://draeger-lab.github.io/SBSCL/ and via Maven Central. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Impact of Cancer Care Regionalization on Patient Volume.

BACKGROUND: Cancer centers are regionalizing care to expand patient access, but the effects on patient volume are unknown. This study aimed to compare patient volumes before and after the establishment of head and neck regional care centers (HNRCCs). METHODS: This study analyzed 35,394 unique new patient visits at MD Anderson Cancer Center (MDACC) before and after the creation of HNRCCs. Univariate regression estimated the rate of increase in new patient appointments. Geospatial analysis evaluated patient origin and distribution. RESULTS: The mean new patients per year in 2006-2011 versus 2012-2017 was 2735 ± 156 patients versus 3155 ± 207 patients, including 464 ± 78 patients at HNRCCs, reflecting a 38.4 % increase in overall patient volumes. The rate of increase in new patient appointments did not differ significantly before and after HNRCCs (121.9 vs 95.8 patients/year; P = 0.519). The patients from counties near HNRCCs, showed a 210.8 % increase in appointments overall, 33.8 % of which were at an HNRCC. At the main campus exclusively, the shift in regional patients to HNRCCs coincided with a lower rate of increase in patients from the MDACC service area (33.7 vs. 11.0 patients/year; P = 0.035), but the trend was toward a greater increase in out-of-state patients (25.7 vs. 40.3 patients/year; P = 0.299). CONCLUSIONS: The creation of HNRCCs coincided with stable increases in new patient volume, and a sizeable minority of patients sought care at regional centers. Regional patients shifted to the HNRCCs, and out-of-state patient volume increased at the main campus, optimizing access for both local and out-of-state patients.

Clinical Diagnosis of the Infantile Shoulder Subluxation in Residual Brachial Plexus Birth Injury and Its Correlation With Ultrasound Diagnosis.

INTRODUCTION AND AIMS OF STUDY: Timely detection of shoulder subluxation in infants with brachial plexus birth injury (BPBI) is essential to prevent the progression of glenohumeral deformity. Shoulder ultrasonography (USG) is routinely used to detect an infantile subluxation/dislocation, but its use is limited because of the paucity of expert radiologists in developing countries. The aim of this study was to determine the clinical examination predictors to determine shoulder subluxation in patients with BPBI correlating with ultrasound confirmation. METHODS: We prospectively studied children who presented to our hospital between 2017 and 2021 diagnosed as brachial plexus birth injury. In patients developing internal rotation contracture of the shoulder, we looked for 3 standard clinical signs: reduced passive external rotation <60 degrees, deep anterior crease (DAC) and relatively short arm segment. Shoulder subluxation was defined as USG measurement of alpha angle>30 degrees and ossific nuclei of the humerus lying behind the dorsal scapular line. Sensitivity and specificity were used to assess their efficacy in clinical diagnosis of shoulder subluxation in different groups. The predicted probability of shoulder subluxation from each prediction rule was compared with actual distributions based on USG confirmation. RESULTS: Of the 58 BPBI infants who developed PER<60 degrees at the shoulder, 41 had USG confirmed shoulder subluxation. The 2 independent predictors of shoulder subluxation (PER<45 degrees and DAC) were identified in the current patient population based on data analysis. The presence of short arm segment is a very specific marker of shoulder subluxation but not sensitive. The predicted probability of shoulder subluxation from the prediction rule combining all the 3 markers were similar to the actual distributions in the current patient population. CONCLUSIONS: PER<45 degrees and presence of deep anterior crease are clinical markers indicating shoulder dislocation in patients with BPBI developing reduced external rotation at the shoulder. On the basis of the proposed clinical diagnosis algorithm, the above markers along with the selective use of USG can help in early detection and treatment of infantile shoulder dislocation.

Mandibular transverse dentoalveolar and skeletal changes associated with lip bumper and rapid maxillary expander: A cone-beam computed tomography study.

INTRODUCTION: Currently, there is little consensus regarding the spontaneous uprighting of the mandibular dentoalveolar complex in response to maxillary expansion, which poses the question about the necessity of combining mandibular treatment with rapid maxillary expansion to coordinate the maxilla and mandible transversely. This study aimed to evaluate the effects of the bonded rapid maxillary expander (RME) alone compared with RME with lip bumper (LB) treatment on the mandibular transverse changes. METHODS: This retrospective study analyzed 3 groups: the control group with no orthodontic or orthopedic treatment (23 patients [14 females, 9 males]; mean age 9.13 years at T1 and 11.24 years at T2); the RME group with no mandibular treatment (22 patients [9 females, 13 males]; mean age 8.73 years at T1 and 12.04 years at T2); and RME + LB group (23 patients [16 females, 7 males]; mean age 9.45 years at T1 and 12.18 years at T2). Three-dimensional superimposition of the mandibular images was performed with cone-beam computed tomography taken at prephase and postphase I treatment (growth and development check records for the control group) to conduct the angular and linear measurements at the dental, alveolar, and skeletal levels. The intergroup comparisons were performed using the Mann-Whitney U-test. RESULTS: Accompanying slight molar self-uprighting during the normal mandibular growth period observed in the control group, transverse growth was also observed in both alveolar and basal bone levels of the mandible, but no significant changes in the alveolar bone inclination occurred. The bonded RME slightly increased the mandibular first molar uprighting but not the mandibular widths at the tooth or alveolar levels. Adding a LB significantly increased the intermolar width and molar uprighting while decreasing the alveolar bone inclination but did not increase the amount of mandibular transverse growth at the bone level. CONCLUSIONS: RME alone did not significantly increase the transverse dimension of the mandible. RME + LB significantly increased mandibular intermolar width, uprighted the mandibular molars, and reduced the alveolar bone inclination.

Clinico-Radiological-Pathological Correlation of Visual Loss in COVID-Associated Rhino-Orbito-Cerebral Mucormycosis.

PURPOSE: To correlate the clinical, radiological, and histopathological features in Covid-associated Rhino-orbito-cerebral mucormycosis cases presenting with acute visual loss. DESIGN: Cross-sectional study. METHODS: Covid-associated Rhino-orbito-cerebral mucormycosis cases with unilateral visual loss, planned for exenteration, underwent orbital and ophthalmological ocular examination. The available radiological sequences, doppler ultrasonography and histopathology findings were correlated with clinical manifestations. RESULTS: The median age was 51 years and the male: female ratio was 3:1. All except one presented with unilateral ophthalmoplegia. The ocular media were hazy in 2 eyes. In 8 eyes, retinal changes were suggestive of occlusion of CRA (6), combined occlusion of CRA and central retinal vein (1), and myopic degeneration with hypertensive retinopathy (1). The contralateral eye showed retinal ischemic changes in one patient. Radiological imaging showed orbital apex involvement in the 10 affected eyes and one contralateral eye. Ipsilateral cavernous sinus thrombosis, diffusion restriction on MRI of optic nerve, internal carotid artery narrowing/thrombosis, and cortical watershed infarcts were seen in 8, 4, 4, and 2 cases, respectively. The blood flow in CRA and ophthalmic artery was absent or reduced in all the 10 affected eyes and in 1 contralateral eye. On histopathology, orbital fat necrosis, fungal hyphae, acute inflammation, granuloma formation, ischemic thrombosis of ophthalmic artery was observed in 10 specimens. CRA was patent in 9 and thrombosed in 1 eye. Optic nerve was ischemic in 8 and viable in 2 eyes. CONCLUSION: Acute visual loss in ROCM cases is associated with orbital apex involvement and thrombotic ischemia of ophthalmic artery. Cessation of flow in CRA possibly occurs secondary to ophthalmic artery thrombosis.

Modified Velpeau Sling Application for the Treatment of Fractures Around Shoulder in Infants.

BACKGROUND: Fractures around the shoulder region in infants are treated by arm-chest bandaging, adhesive strapping, or sling application. These conventional treatment methods are associated with issues like skin irritation, excoriation, movement of bone fragments causing muscle spasm, and difficulty in nursing care. We describe the technique of modified Velpeau sling application and reviewed its efficacy at a long-term follow-up. METHODS: A retrospective study was conducted with 19 infants who presented between 2009 and 2018 to a tertiary care center in western India with either clavicle or humerus fracture. Inclusion criteria was any infant with humerus or clavicle fracture that underwent modified Velpeau sling application and had a minimum follow-up of 2 years. Patients were followed at weekly intervals until sling discontinuation based on the fracture healing. At further follow-up, children were assessed for the presence of angular or rotational malalignment and limb length discrepancy. Functional outcome was measured by the Paediatric Adolescent Shoulder Survey at the final follow-up. RESULTS: Seven clavicle and 12 humerus fractures were treated with this technique. The mean age at presentation was 50 days (range, 1 d to 7 mo). The average follow-up was 6 years (range, 2 to 10 y). Two infants had underlying osteogenesis imperfecta. Infants without underlying pathology had no angular/rotational malalignment or limb length discrepancy, while both infants with underlying osteogenesis imperfecta had a varus alignment and shortening of the humerus. Infants without underlying pathology demonstrated good functional outcomes measured by the Paediatric Adolescent Shoulder Survey questionnaire, while those with pathology had functional limitations. CONCLUSIONS: The modified Velpeau method is an effective way of treating fractures around the shoulder region in infants without underlying pathology. Several advantages such as accessibility of sling material, easy application, inexpensive material, and absence of skin-related complications make this an effective treatment. LEVEL OF EVIDENCE: Level IV-therapeutic study.

Correlating the patterns of diabetic macular edema, optical coherence tomography biomarkers and grade of diabetic retinopathy with stage of renal disease.

PURPOSE: To correlate optical coherence tomography (OCT)-based morphological patterns of diabetic macular edema (DME), biomarkers and grade of diabetic retinopathy (DR) in patients with various stages of chronic kidney disease (CKD) secondary to diabetes. DESIGN: Multicentric retrospective cross-sectional study was conducted at seven centers across India. METHODS: Data from medical records of patients with DME and CKD were entered in a common excel sheet across all seven centers. Staging of CKD was based on estimated glomerular filtration rate (eGFR). RESULTS: The most common morphological pattern of DME was cystoid pattern (42%) followed by the mixed pattern (31%). The proportion of different morphological patterns did not significantly vary across various CKD stages (p = 0.836). The presence of external limiting membrane-ellipsoid zone (ELM-EZ) defects (p < 0.001) and foveal sub-field thickness (p = 0.024) showed a direct correlation with the stage of CKD which was statistically significant. The presence of hyperreflective dots (HRD) and disorganization of inner retinal layers (DRIL) showed no significant correlation with the stage of CKD. Sight threatening DR was found to increase from 70% in CKD stage 3 to 82% in stages 4 and 5 of CKD, and this was statistically significant (p = 0.03). CONCLUSION: Cystoid morphological pattern followed by mixed type was the most common pattern of DME on OCT found in patients suffering from stage 3 to 5 of CKD. However, the morphological patterns of DME did not significantly vary across various CKD stages. ELM-EZ defects may be considered as an important OCT biomarker for advanced stage of CKD.

Proton Therapy for HPV-Associated Oropharyngeal Cancers of the Head and Neck: a De-Intensification Strategy.

OPINION STATEMENT: The rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT-all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway-the "Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck" and the "TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)" trial-are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.

A Biomechanical Comparison of the Effect of Baseplate Design and Bone Marrow Fat Infiltration on Tibial Baseplate Pullout Strength.

BACKGROUND: Early clinical results of a new total knee arthroplasty (TKA) implant design show promise for improved outcomes and patellofemoral function scores. However, reports of early tibial component-cement interface debonding requiring revision have been published. This study investigated the biomechanical properties of three different tibial baseplates to understand potential causes of failure. METHODS: PFC Sigma (control), Attune (1st generation) and Attune S+ (2nd generation) tibial baseplates were implanted into 4th generation sawbone tibia models using a standardized technique. Three of each baseplate were cemented with and without additional bovine bone marrow fat. All models were tested to failure with measured axial distraction force. Implant type, presence or absence of bovine marrow and load to failure were all recorded and compared. Two-way ANOVA followed by post-hoc pairwise comparisons were used to determine statistical significance, which was set to P < .05. RESULTS: The 2nd generation tibial baseplates required significantly more force to failure. The presence of bovine marrow significantly reduced the pullout force of the implant designs overall. No significant difference was detected between the 1st generation and control baseplates. Failure mode for each model was also noted to be different irrespective of the presence or absence of bone marrow fat. CONCLUSION: The 2nd generation baseplates required significantly more force to failure compared with older designs. The presence of bone marrow during cementation of a tibial base plate significantly decreased axial pullout strength of a tibial baseplate in this laboratory model. All 1st generation baseplates exhibited debonding at the cement-implant interface.

Using Strand Displacing Polymerase To Program Chemical Reaction Networks.

Chemical reaction networks (CRNs) provide a powerful abstraction to formally represent complex biochemical processes. DNA provides a promising substrate to implement the abstract representation (or programming language) of CRNs due to its programmable nature. Prior works that used DNA to implement CRNs either used DNA-only systems or multienzyme DNA circuits. Architectures with DNA-only components had the rationale of being biologically simple systems. Multienzyme systems, on the other hand, aimed at using natural enzymes to improve circuit performance, although, at the cost of increased complexity. In this work, we explore an alternative architecture that lies along the spectrum in between DNA-only systems and multienzyme DNA systems. Our architecture relies on only a strand displacing polymerase enzyme and DNA hybridization reactions for implementing CRNs. First, we briefly introduce the theory and DNA design of simple CRNs and then explore the fundamental properties of polymerase-based strand displacement systems. Finally, we engineer a catalytic amplifier in vitro as a use-case of our framework since such amplifiers require the intricate design of DNA sequences and reaction conditions.

Programming Temporal DNA Barcodes for Single-Molecule Fingerprinting.

Fluorescence microscopy enables simultaneous observation of the dynamics of single molecules in a large region of interest. Most traditional techniques employ either the geometry or the color of single molecules to uniquely identify (or barcode) different species of interest. However, these techniques require complex sample preparation and multicolor hardware setup. In this work, we introduce a time-based amplification-free single-molecule barcoding technique using easy-to-design nucleic acid strands. A dye-labeled complementary reporter strand transiently binds to the programmed nucleic acid strands to emit temporal intensity signals. We program the DNA strands to emit uniquely identifiable temporal signals for molecular-scale fingerprinting. Since the reporters bind transiently to DNA devices, our method offers relative immunity to photobleaching. We use a single universal reporter strand for all DNA devices making our design extremely cost-effective. We show DNA strands can be programmed for generating a multitude of uniquely identifiable molecular barcodes. Our technique can be easily incorporated with the existing orthogonal methods that use wavelength or geometry to generate a large pool of distinguishable molecular barcodes thereby enhancing the overall multiplexing capabilities of single-molecule imaging.

Vitamin C and inflammatory cytokine levels in elective total knee arthroplasty.

BACKGROUND: Vitamin C levels are decreased in arthritis patients and reduced levels following surgery may impair adequate healing. AIM: This study measured changes in vitamin C and inflammatory markers in patients undergoing total knee arthroplasty (TKA). METHODS: Venous blood samples were collected from 10 patients during the preoperative to postoperative period. Vitamin C, interleukin-1ß, interleukin-6 (IL-6), and C-reactive protein (CRP) levels were measured using various assays. RESULTS: No significant changes in vitamin C levels were measured. However, all participants had suboptimal preoperative vitamin C levels and 90% had suboptimal levels postoperatively. IL-6 and CRP levels significantly increased during the immediate postoerative period. CONCLUSION: There was a rise in inflammation following TKA while vitamin C levels did not significantly change during this short study period. Of note, every patient had suboptimal vitamin C levels prior to surgery and 90% continued with suboptimal levels two days postoperatively.

Programming DNA-Based Biomolecular Reaction Networks on Cancer Cell Membranes.

DNA is a highly programmable biomolecule and has been used to construct biological circuits for different purposes. An important development of DNA circuits is to process the information on receptors on cell membranes. In this Communication, we introduce an architecture to program localized DNA-based biomolecular reaction networks on cancer cell membranes. Based on our architecture, various types of reaction networks have been experimentally demonstrated, from simple linear cascades to reaction networks of complex structures. These localized DNA-based reaction networks can be used for medical applications such as cancer cell detection. Compared to prior work on DNA circuits for evaluating cell membrane receptors, the DNA circuits made by our architecture have several major advantages including simpler design, lower leak, lower cost, and higher signal-to-background ratio.

Effect of Reverse End-to-Side (Supercharging) Neurotization in Long Processed Acellular Nerve Allograft in a Rat Model.

PURPOSE: Processed acellular nerve allograft (PNA) has been suggested as a convenient tool for overcoming short and medium nerve defects. Although the clinical implications are unclear, animal data suggest that PNA becomes less effective at longer lengths. Although reverse or supercharging end-to-side nerve transfer may improve the neurotrophic potential in chronically denervated nerve tissue, the application of this strategy to long acellular nerve allograft has not been previously investigated. We hypothesized that supercharging acellular nerve allograft would increase its effective length. METHODS: Sprague-Dawley and Thy1-green fluorescent protein Sprague-Dawley rats underwent transection of the tibial nerve, followed by immediate repair with 20-, 40-, or 60-mm acellular nerve allografts processed identically to commercially available human acellular nerve allograft (AxoGen, Inc., Alachua, FL) or isograft. Half of the allograft group was supercharged with a reverse end-to-side transfer from the ipsilateral peroneal nerve. At 10 weeks, the reconstructed nerve in the Thy1-green fluorescent rat groups were exposed and examined under a fluorescence-enabled microscope. At 20 weeks, the remaining rats underwent motor testing and tissue harvest for morphological examination. RESULTS: In comparison with a nonenhanced allograft, supercharging had a statistically significant positive impact on the reinnervated muscle normalized force generation and distal axon counts for all graft sizes. Muscles in the supercharged group were heavier than those in the allograft group for the 40-mm-length grafts and G-ratio measurements were higher in the supercharged allograft group for 60-mm-length grafts only. CONCLUSIONS: This study supports that hypothesis that supercharging nerve transfer improves axon regeneration within PNA. CLINICAL RELEVANCE: When an appropriate donor nerve is available, supercharging nerve transfer may improve nerve regeneration in PNA across long nerve defects.

Renewable Time-Responsive DNA Circuits.

DNA devices have been shown to be capable of evaluating Boolean logic. Several robust designs for DNA circuits have been demonstrated. Some prior DNA-based circuits are use-once circuits since the gate motifs of the DNA circuits get permanently destroyed as a side effect of the computation, and hence cannot respond correctly to subsequent changes in inputs. Other DNA-based circuits use a large reservoir of buffered gates to replace the working gates of the circuit and can be used to drive a finite number of computation cycles. In many applications of DNA circuits, the inputs are inherently asynchronous, and this necessitates that the DNA circuits be asynchronous: the output must always be correct regardless of differences in the arrival time of inputs. This paper demonstrates: 1) renewable DNA circuits, which can be manually reverted to their original state by addition of DNA strands, and 2) time-responsive DNA circuits, where if the inputs change over time, the DNA circuit can recompute the output correctly based on the new inputs, that are manually added after the system has been reset. The properties of renewable, asynchronous, and time-responsiveness appear to be central to molecular-scale systems; for example, self-regulation in cellular organisms.

A Single Institution Retrospective Comparison Study of Locoregional Recurrence After Accelerated Partial Breast Irradiation Using External Beam Fractionation Compared with Whole Breast Irradiation with 8 Years of Follow-Up.

BACKGROUND: Accelerated partial breast irradiation (APBI) was developed to address disadvantages of overall treatment time and potentially unnecessary radiation associated with whole breast irradiation (WBI). We report updated results of our single institution study using an external beam APBI regimen with a median follow-up of 8 years. METHODS: A total of 290 APBI patients with AJCC Stage 0-II breast cancer were compared with 290 WBI patients with matched tumor characteristics. Toxicities were scored based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Cox regression models were used to predict likelihood of freedom from ipsilateral failure. RESULTS: Median follow-up was 8 years in the APBI group and 7.5 years in the WBI group. In the APBI group, there were 18 (6.2%) ipsilateral breast tumor recurrence (IBTR), 13 (72%) had elsewhere failures (EF), and 5 (28%) had local failures (LF) with a median time to failure of 64.1 months. In the WBI group, there were three (1.0%) IBTR; one (33%) was an EF and two (67%) were LF with a median time to failure of 91 months. APBI was 4.6 times more likely (hazard ratio 4.57, 95% confidence interval 1.3-16.2, p = 0.02) to have an IBTR than WBI after adjusting for age, tumor size, histology, grade, and estrogen receptor status. Fatigue, erythema, and desquamation toxicities were significantly less in the APBI group then the WBI group. CONCLUSIONS: IBTR rates were higher in external beam APBI group compared with WBI, but APBI had fewer toxicities. Clinicians must weigh the risks and benefits of APBI when making a recommendation for partial breast irradiation after lumpectomy.

Does partial muscle reinnervation preserve future re-innervation potential?

INTRODUCTION: Late revision nerve surgery for incomplete motor recovery due to partial reinnervation would improve muscle function if all muscle fibers were protected from developing denervation atrophy. METHODS: Sixty immature Sprague-Dawley rats underwent the following tibial nerve manipulations (n = 15/group): group A, partial denervation (two thirds of nerve resected and the remaining one third crushed), revision repair at 8 months; group B, partial denervation; group C, complete denervation, immediate reconstruction; group D, complete denervation, reconstruction at 8 months; and group E, control. Final testing at 11 months included muscle force, weight, and histology. RESULTS: Muscle weight was significantly (P < 0.05) different among all groups (highest to lowest: E > B > C > A > D), and force was significantly lower in groups A and D compared with E. Muscle fiber cross-sectional area was statistically smaller in group A than in groups B, C, or E. DISCUSSION: Partial reinnervation still allowed substantial muscle recovery, but it did not preserve the non-innervated muscle fibers. Muscle Nerve 56: 1143-1148, 2017.

Microsporidial polymyositis in human immunodeficiency virus-infected patients, a rare life-threatening opportunistic infection: clinical suspicion, diagnosis, and management in resource-limited settings.

INTRODUCTION: Microsporidial myositis is a rare opportunistic infection that has been reported in HIV-infected and HIV-uninfected immunocompromised patients. METHODS: In this study we present a retrospective analysis of 5 cases of microsporidial myositis in HIV-infected patients, including the clinical, laboratory, and histologic features, and a review of the literature. RESULTS: Five young men with HIV infection [median CD4 count of 20 cells (range 14-144)/mm(3) ] who presented with signs and symptoms suggestive of myositis underwent EMG-NCV and muscle biopsy, which revealed signs compatible with microsporidial myositis. Early and aggressive treatment led to improvement in 3 patients. Two of the 5 patients died due to a delay in diagnosis, because the spores were mistaken for Candida without confirmatory stains or a high index of suspicion. CONCLUSIONS: Myositis in HIV-infected patients with low CD4 counts should be evaluated using muscle biopsy. A high index of suspicion is required for early diagnosis of microsporidial myositis in HIV-infected patients. Early diagnosis and immediate, aggressive treatment are the keys to favorable outcomes in these patients.