2D Nanomaterials and Their Drug Conjugates for Phototherapy and Magnetic Hyperthermia Therapy of Cancer and Infections.

Photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) using 2D nanomaterials (2DnMat) have recently emerged as promising alternative treatments for cancer and bacterial infections, both important global health challenges. The present review intends to provide not only a comprehensive overview, but also an integrative approach of the state-of-the-art knowledge on 2DnMat for PTT and MHT of cancer and infections. High surface area, high extinction coefficient in near-infra-red (NIR) region, responsiveness to external stimuli like magnetic fields, and the endless possibilities of surface functionalization, make 2DnMat ideal platforms for PTT and MHT. Most of these materials are biocompatible with mammalian cells, presenting some cytotoxicity against bacteria. However, each material must be comprehensively characterized physiochemically and biologically, since small variations can have significant biological impact. Highly efficient and selective in vitro and in vivo PTTs for the treatment of cancer and infections are reported, using a wide range of 2DnMat concentrations and incubation times. MHT is described to be more effective against bacterial infections than against cancer therapy. Despite the promising results attained, some challenges remain, such as improving 2DnMat conjugation with drugs, understanding their in vivo biodegradation, and refining the evaluation criteria to measure PTT or MHT effects.

Ageing in the brain: mechanisms and rejuvenating strategies.

Ageing is characterized by the progressive loss of cellular homeostasis, leading to an overall decline of the organism's fitness. In the brain, ageing is highly associated with cognitive decline and neurodegenerative diseases. With the rise in life expectancy, characterizing the brain ageing process becomes fundamental for developing therapeutic interventions against the increased incidence of age-related neurodegenerative diseases and to aim for an increase in human life span and, more importantly, health span. In this review, we start by introducing the molecular/cellular hallmarks associated with brain ageing and their impact on brain cell populations. Subsequently, we assess emerging evidence on how systemic ageing translates into brain ageing. Finally, we revisit the mainstream and the novel rejuvenating strategies, discussing the most successful ones in delaying brain ageing and related diseases.

New graphene-containing pharmaceutical formulations for infrared lamps-based phototherapy of skin cancer: In vitro validation and ex-vivo human skin permeation.

Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm-2), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 µg mL-1) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 µg mL-1) completely eradicated skin cancer cells (A-431). Ex vivo human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 µg mL-1) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG.

Greater tuberosity fractures of the humerus: complications and long-term outcomes after surgical treatment.

BACKGROUND: Isolated greater tuberosity (GT) fractures typically occur in younger patients following high-energy trauma compared to humeral neck fractures. Surgical treatment is indicated when superior displacement is > 5 mm. This study aimed to assess the complications and long-term outcomes of surgically-treated GT fractures. METHODS: A retrospective review of 39 patients who underwent surgery from 2010 to 2014 was conducted. The cohort comprised 54.6% females, with an average age of 56.74 years and a median follow-up of 6.71 years. Only 25 patients returned for reevaluation, with functional outcomes assessed using Constant-Murley score. RESULTS: Women were older than men (63.00 ± 12.15 vs. 48.65 ± 16.93, p = 0.006). 18/39 patients (46.1%) sustained avulsion-type, 1 patient out of 39 (2.6%) depression-type, and 20/39 patients (51.3%) split-type fractures. The mean Constant-Murley score was 84.08 ± 18.36, with higher scores observed in men (p = 0.021). Avulsion-type fractures were related to higher postoperative scores compared to split fractures (p = 0.069). Post-surgical complications occurred in 20.5% of patients, with no differences noted between sexes, fracture types, or procedures. CONCLUSION: This study enhances understanding of the long-term outcomes of surgically-treated GT fractures, aiding in treatment selection. Interfragmentary screws may be preferable in younger male patients, but are associated with the higher risk of reintervention, particularly in fragile bone. Prospective multicentric studies are warranted to further elucidate long-term results and treatment strategies.

Chemotherapy-free treatment of recurrent advanced ovarian cancer: myth or reality?

Advanced ovarian cancer remains a leading cause of death from gynecologic malignancy. Surgery and, in most cases, platinum-based chemotherapy with or without maintenance with bevacizumab and/or poly-ADP ribose polymerase inhibitors (PARPi) represent the mainstay of treatment, but the disease typically recurs. The treatment of these patients represents a clinical challenge because sequential chemotherapy regimens are often used, with suboptimal outcomes and cumulative toxicity. Chemotherapy-free regimens, based on combinations of PARPi, vascular endothelial growth factor receptor inhibitors, anti-programmed cell death protein-1/programmed death-ligand 1, and anti-cytotoxic T-lymphocyte-associated protein-4 antibodies, among others, represent a valid option, with manageable toxicity profile and ease of administration. This review addresses this new strategy in the management of recurrent ovarian cancer and discusses its feasibility in the treatment landscape of the disease.

Innovative, Sugar-Free Oral Hydrogel as a Co-administrative Vehicle for Pediatrics: a Strategy to Enhance Patient Compliance.

Palatability and swallowability in the pediatric population are perceived as true challenges in the oral administration of medication. Pediatric patients have high sensitivity to taste and reduced ability to take solid dosage forms, which can often lead to a poor therapeutic compliance. It is crucial to find new strategies to simplify the oral administration of drugs to children. The present paper reports the development of a new hydrogel vehicle adapted to the pediatric population. Several polymers with similar properties were selected and adjustments were made to obtain the desired characteristics of the final product. The developed formulations were studied for organoleptic properties, rheology, mucoadhesion properties, preservative efficacy, and stability. Physical and chemical compatibilities between the vehicle and several drugs/medicines, at the time of administration, were also studied. Six final formulations with different polymers, odor, and color were chosen, and no known interactions with medications were observed. The proposed new oral vehicles are the first sugar-free vehicle hydrogels designed to make the intake of oral solid forms a more pleasant and safer experience for pediatric patients.

SARS-CoV-2 infection in kidney transplant recipients: Early report of five cases.

From December 2019 to March 2020, China was the epicenter of the SARS-CoV-2 infection pandemic, but from that moment on, Europe surpassed China in the number of new cases and deaths related to this novel viral respiratory infection. The emergence of this world pandemic is particularly important for solid organ transplant recipients, who might have an increased risk of mortality, not only due to their chronic immunosuppression status, but also to the cardiovascular risk that correlates with several years of chronic kidney disease. To the extent that there is still a lack of knowledge about the clinical characteristics, evolution, and prognosis of SARS-CoV-2 infection in kidney transplant recipients, we will report the first 5 cases diagnosed and followed in our transplant unit, as well as share the therapeutic strategies adopted.

The Proinflammatory Soluble CD40 Ligand Is Associated with the Systemic Extent of Stable Atherosclerosis.

Background and objectives: Polyvascular atherosclerosis is frequent and associated with a high cardiovascular risk, although the mechanisms regulating the atherosclerosis extent to single or multiple arterial territories are still poorly understood. Inflammation regulates atherogenesis and soluble CD40 ligand (sCD40L) is an inflammatory mediator associated with the presence of single-territorial atherosclerosis. We assessed whether the sCD40L expression is associated with the atherosclerosis extent to single or multiple arterial territories and with the atherosclerosis severity in different territories. Materials and Methods: We prospectively enrolled 94 participants with no atherosclerosis (controls, n = 26); isolated coronary atherosclerosis (group 1, n = 20); coronary and lower extremity (LE) atherosclerosis (group 2, n = 18); coronary and carotid atherosclerosis (group 3, n = 12); and coronary, LE, and carotid atherosclerosis (group 4, n = 18). Serum sCD40L levels were quantified. Results: The sCD40L levels (ng/mL, mean (standard deviation)) were 4.0 (1.5), 5.6 (2.6), 7.2 (4.2), 5.9 (3.7), and 5.1 (2.4) in controls and groups 1 to 4, respectively (ANOVA p = 0.012). In nonrevascularized patients, the sCD40L levels were significantly higher in group 2 than in group 1 and were correlated with the number of LE diseased segments. Prior LE bypass surgery was associated with lower sCD40L levels. Coexistence of coronary and LE atherosclerosis was independently associated with the sCD40L levels. Conclusions: The sCD40L levels were increased in stable atherosclerosis, particularly in polyvascular coronary and LE atherosclerosis. The number of LE diseased segments and prior LE revascularization were associated with sCD40L expression. To our knowledge, these are novel data, which provide insights into the mechanisms underlying multi-territorial atherosclerosis expression. sCD40L may be a promising noninvasive tool for refining the stratification of the systemic atherosclerotic burden.

Association between miR-146a and Tumor Necrosis Factor Alpha (TNF-α) in Stable Coronary Artery Disease.

Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7-1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-α levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-α levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (ΔCt) miR-146a and TNF-α levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-α levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between ΔCt miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-α levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-α-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.

Framework to Support the Process of Decision-Making on Life-Sustaining Treatments in the ICU: Results of a Delphi Study.

OBJECTIVES: To develop a consensus framework that can guide the process of decision-making on continuing or limiting life-sustaining treatments in ICU patients, using evidence-based items, supported by caregivers, patients, and surrogate decision makers from multiple countries. DESIGN: A three-round web-based international Delphi consensus study with a priori consensus definition was conducted with experts from 13 countries. Participants reviewed items of the decision-making process on a seven-point Likert scale or with open-ended questions. Questions concerned terminology, content, and timing of decision-making steps. The summarized results (including mean scores) and expert suggestions were presented in the subsequent round for review. SETTING: Web-based surveys of international participants representing ICU physicians, nurses, former ICU patients, and surrogate decision makers. PATIENTS: Not applicable. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: In three rounds, respectively, 28, 28, and 27 (of 33 invited) physicians together with 12, 10, and seven (of 19 invited) nurses participated. Patients and surrogates were involved in round one and 12 of 27 responded. Caregivers were mostly working in university affiliated hospitals in Northern Europe. During the Delphi process, most items were modified in order to reach consensus. Seven items lacked consensus after three rounds. The final consensus framework comprises the content and timing of four elements; three elements focused on caregiver-surrogate communication (admission meeting, follow-up meeting, goals-of-care meeting); and one element (weekly time-out meeting) focused on assessing preferences, prognosis, and proportionality of ICU treatment among professionals. CONCLUSIONS: Physicians, nurses, patients, and surrogates generated a consensus-based framework to guide the process of decision-making on continuing or limiting life-sustaining treatments in the ICU. Early, frequent, and scheduled family meetings combined with a repeated multidisciplinary time-out meeting may support decisions in relation to patient preferences, prognosis, and proportionality.

Short Total Synthesis of Ajoene, (E,Z)-4,5,9-Trithiadodeca-1,6,11-triene 9-oxide, in Batch and (E,Z)-4,5,9-Trithiadodeca-1,7,11-triene in Continuous Flow.

A short total synthesis of ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, has been achieved over six steps. In addition, a continuous flow synthesis under mild reaction conditions to (E,Z)-4,5,9-trithiadodeca-1,7,11-triene is described starting from simple and easily accessible starting materials. Over four steps including propargylation, radical addition of thioacetate, deprotection, and disulfide formation/ allylation, the target product can be obtained at a rate of 0.26 g h-1 in an overall yield of 12 %.

Lower donated kidney volume is associated with increased risk of lower graft function and acute rejection at 1 year after living donor kidney-a retrospective study.

Kidney volume has been proven to be a surrogate marker of nephron mass and renal function. We studied 190 donor and recipient pairs undergoing living donor kidney transplantation at our institution during 9 years. Different metrics of donor kidney volume (DKV) were explored: alone or indexed to recipient's anthropometry, as body surface area (BSA). DKV/BSA (min. 49.7; P33rd 77.7; P67th 95.3; max. 176 cm3 /m2 ) was chosen given its higher correlation with eGFR at 1 year, and recipients were divided according to its tertiles (T). The eGFR at 1 year was lower in T1, when compared with T2 (P = 0.015) and T3 (P < 0.001). In a multivariable model, a regression spline revealed that a DKV/BSA lower than 80 was significantly associated with an eGFR at 1 year <60. In the first 6 years, the overall annual eGFR slope was -0.90 ml/min/year. Acute rejection occurred in 19%, 11%, and 0% of patients in T1, T2, and T3, respectively (P < 0.001). DKV/BSA increased stepwise from cellular- (n = 12) to antibody-mediated (n = 7) AR cases and to those without AR (n = 171; P = 0.002; no AR versus cellular AR). Lower DKV/BSA ratio was associated with significantly worse graft function and higher incidence of AR. Hence, it can be a tool for better selection of donors in order to improve graft outcomes, particularly in the setting of multiple potential living donors or kidney paired exchange programs.

Remaining kidney volume indexed to weight as a strong predictor of estimated glomerular filtration rate at 1 year and mid-term renal function after living-donor nephrectomy - a retrospective observational study.

The donors' estimated glomerular filtration rate (eGFR) after living nephrectomy has been a concern, particularly in donors with smaller kindeys. Therefore, we developed this retrospective observational study in 195 donors to determine the ability remaining kidney volume indexed to weight (RKV/W) to predict eGFR at 1 year through multivariate linear regression and to explore this relationship between annual eGFR change from 1 to 4 years postdonation evaluated by a linear mixed model. Comparing RKV/W tertiles (T1, T2, T3), RKV/W was a good predictor of 1-year eGFR which was significantly better in T3 donors. Gender, predonation eGFR, and RKV/W were independent predictors of eGFR at 1-year. In a subgroup with predonation eGFR < 90mL/min/1.73 m2 , a significant prediction of eGFR < 60mL/min/1.73 m2 was detected in males with RKV/W ≤ 2.51cm3 /kg. Annual eGFR (ml/min/year) change from 1 to 4 years was + 0.77. RKV/W divided by tertiles (T1-T3) was the only significant predictor: T2 and T3 donors had an annual eGFR improvement opposing to T1. RKV/W was a good predictor of eGFR at 1 year, independently from predonation eGFR. A higher RKV/W was associated with improved eGFR at 1 year. A decline in eGFR on the four years after surgery was only noticeable in donors with RKV/W ≤ 2.13cm3 /kg.

Evaluating Skin Sensitization Via Soft and Hard Multivariate Modeling.

Allergic contact dermatitis is the most frequent manifestation of immunotoxicity in humans with a prevalence rate of 15% to 20% over general population. Skin sensitization is a complex end point that was for a long time being evaluated using animal testing. Great efforts have been made to completely substitute the use of animals and replace them by integrating data from in vitro and in chemico assays with in silico calculated parameters. However, it remains undefined how to make the best use of the cumulative data in such a way that information gain is maximized and accomplished with the fewest number of tests possible. In this work, 3 skin sensitization prediction models were considered: one to discriminate sensitizers from non-sensitizers, considering a 2-level scale; one according to the GHS, considering a 3-level scale; and the other to categorize potency in a 6-level scale, according to available human data. We used a data set of known human skin allergens for which in vitro, in chemico, and in silico descriptors where available to build classifiers based on soft and hard multivariate modeling. Model building, optimization, and refinement resulted in 100% accuracy in distinguishing between sensitizers and non-sensitizers. The same model was able to perform the characterization, in 3 and 6 levels, respectively, with 98.8 and 97.5% accuracy. Combining data from in vitro and in chemico tests with in silico descriptors is relatively simple to implement and some predictors are fitting the adverse outcome pathway for skin sensitization.

New insights in cryoglobulinemic vasculitis.

Cryoglobulins are antibodies that precipitate at low temperatures and dissolve after rewarming. Cryoglobulinemia refers to the presence of circulating cryoglobulins and generally leads to a systemic inflammatory syndrome characterized by fatigue, arthralgia, purpura, ulcers, neuropathy and/or glomerulonephritis. The disease mainly involves small to medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes. Cryoglobulinemia is classified into three types (I, II and III) on the basis of immunoglobulin composition. Predisposing conditions include lymphoproliferative, autoimmune diseases and hepatitis C virus infection. The diagnosis of cryoglobulinemic syndrome is predominantly based on the presence of clinical features and laboratorial demonstration of serum cryoglobulins. The treatment strategy depends on the cause of cryoglobulinemia. For patients with chronic HCV infection, antiviral therapy is indicated. Immunosuppressive or immunomodulatory therapy, including steroids, plasmapheresis and cytotoxic agents, is reserved for organ-threatening manifestations. In this review, we discuss the main clinical presentations, diagnostic approach and treatment options.

Differential expression of gonadotropin and estrogen receptors and oocyte cytology during follicular maturation associated with egg viability in European eel (Anguilla anguilla).

In captivity, oogenesis and ovarian follicle maturation in European eel can be induced experimentally using hormonal therapy. The follicle's ability to respond effectively to the induction of maturation and ovulation, resulting in viable eggs, depends on the oocyte stage at the time of induction. We hypothesized that variation in the expression of key hormone receptors in the ovary and size of oocyte lipid droplets are associated with changes in oocyte stage. Thus, we induced ovarian follicle maturation using a priming dose of fish pituitary extract followed by the administration of a 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) injection. Females were then strip-spawned, the eggs were fertilized in vitro, incubated and larval survival was recorded at 3 days post hatch (dph). The expression of gonadotropin receptors (fshr, lhcgr1 and lhcgr2) and estrogen receptors (esr1, esr2a, esr2b, gpera and gperb) was quantified and the size of oocyte lipid droplets measured. Larval survival at 3 dph was used to differentiate high- and low-quality egg batches. Results showed significantly higher abundance of lhcgr1 and esr2a at priming for high-quality egg batches whereas fshr and gperb transcripts were significantly higher at DHP injection for low-quality egg batches. Therefore, high levels of lhcgr1 and esr2a may be important for attaining follicular maturational competence, while high fshr and gperb mRNA levels may indicate inadequate maturational competence. Furthermore, lipid droplet size at DHP and in ovulated eggs was significantly smaller in high-quality egg batches than in low-quality, which indicates that droplet size may be a useful marker of follicular maturational stage.

Short Total Synthesis of Ajoene.

We describe a short total synthesis of ajoene, a major biologically active constituent of garlic. The instability of allicin as the only other known alternative starting material has led to the development of a reliable procedure for the synthesis of ajoene from simple building blocks that is also suitable for upscale operations.

High pressure inactivation of Brettanomyces bruxellensis in red wine.

Brettanomyces bruxellensis ("Brett") is a major spoilage concern for the wine industry worldwide, leading to undesirable sensory properties. Sulphur dioxide, is currently the preferred method for wine preservation. However, due to its negative effects on consumers, the use of new alternative non-thermal technologies are increasingly being investigated. The aim of this study was to determine and model the effect of high pressure processing (HPP) conditions and yeast strain on the inactivation of "Brett" in Cabernet Sauvignon wine. Processing at 200 MPa for 3 min resulted in 5.8 log reductions. However higher pressure is recommended to achieve high throughput in the wine industry, for example >6.0 log reductions were achieved after 400 MPa for 5 s. The inactivation of B. bruxellensis is pressure and time dependent, with increased treatment time and pressure leading to increased yeast inactivation. It was also found that yeast strain had a significant effect on HPP inactivation, with AWRI 1499 being the most resistant strain. The Weibull model successfully described the HPP "Brett" inactivation. HPP is a viable alternative for the inactivation of B. bruxellensis in wine, with the potential to reduce the industry's reliance on sulphur dioxide.

Nystatin and lidocaine pastilles for the local treatment of oral mucositis.

Oral mucositis (OM) is a common adverse reaction to radiotherapy and chemotherapy in oncology. Its treatment requires oral formulations that enhance therapy compliance, improve administration and ensure drug effectiveness. Solid dosage forms that act by slow dissolution, such as pastilles, are an effective alternative to mouthwashes, for their versatility, ease of administration and extended residence time in the oral cavity. The present work describes the development and stability studies of an innovative formulation of nystatin and lidocaine pastilles for the treatment of oral mucositis. Full pharmaceutical quality testing was carried out, including disintegration and dissolution testing, texture profile analysis, grittiness and an antifungal activity testing. A soft pastille formulation containing 0.25% lidocaine and 78,000 IU nystatin was obtained, presenting suitable pharmaceutical characteristics, as a disintegration time of 17 ± 2 min, dissolution rate and microbiological and physicochemical for 30 days when stored at 2-8 °C under light protection. Palatability was also evaluated, being well accepted by a panel of 38 healthy volunteers. This formulation allows an accurate drug dosing by the prescriber, while enabling the patients to control the retention time of the drugs in the oral cavity and consequently manage their pain treatment.

The Acute Effect of Cryotherapy on Muscle Strength and Shoulder Proprioception.

CONTEXT: Cryotherapy, a common intervention used by clinicians, poses several benefits in managing acute injuries. However, cooling muscle tissue can interfere with muscular properties and the sensory-motor system. OBJECTIVE: The aim of this study was to analyze the influence of cryotherapy with a crushed-ice pack on shoulder proprioception concerning joint position sense, force sense, the threshold for detecting passive movement, and maximal force production. DESIGN: A randomized, double-blind controlled trial. PARTICIPANTS: 48 healthy women aged 22.6 ± 0.4 y with a mean body mass index of 22.8 ±0.37 kg/m2 and a percentage of body fat of 15.4 ± 1.5%. METHODS: In the experimental group, a crushed-ice pack was applied to the shoulder for 15 min, whereas participants in the control group applied a sandbag at skin temperature, also for 15 min. An isokinetic dynamometer was used to assess maximal voluntary contraction, force sense, joint position sense, and the threshold for detecting passive movement. RESULTS: Paired sample t tests revealed that maximal voluntary isometric contraction decreased significantly after cryotherapy (P ≤ .001), or approximately 10% of the reduction found in both muscular groups assessed. Shoulder position sense (P < .001) and the threshold for detecting passive movement (P = .01 and P = .01 for lateral and medial shoulder rotator muscles, respectively) also suffered significant impairment. Nevertheless, no significant differences emerged in force sense at 20% and 50% of maximal force reproduction (P = .41 and P = .10 for lateral rotator muscles at 20% and 50%, respectively; and P = .20 and P = .09 for medial rotator muscles at 20% and 50%, respectively). CONCLUSION: Applying a crushed-ice pack to the shoulder for 15 min negatively affected muscle strength and impaired shoulder proprioception by decreasing joint position sense and the threshold for detecting passive movement.