Laparoscopic Lumen-guided cholecystectomy in face of the difficult gallbladder.

BACKGROUND: Where the critical view of safety cannot be established during cholecystectomy, certain salvage techniques are indicated to reduce the likelihood of bile duct injury. The present study describes a salvage technique termed the "laparoscopic lumen-guided cholecystectomy" (LLC) and reports its peri-operative outcomes. METHOD: A summary of the technique is as follows: (1) Hartmann's pouch is incised and stones are evacuated; (2) the cystic anatomy is inspected from the inside of the gallbladder; (3) the lumen is used to guide retrograde dissection towards the cystic pedicle; (4) cystic duct control is achieved if deemed safe. LLC cases performed between June 2020 and January 2022 in a single health board were included. The operative details and peri-operative outcomes of the technique are reported and compared to cases of similar difficulty where the LLC was not attempted. RESULTS: LLC was performed in 4.6% (27/587) of cases. In all 27 cases, LLC was performed for a "frozen" cholecystohepatic triangle. Hartmann's pouch was completely excised in all cases (27/27) and cystic duct control was achieved in 85.2% of cases (23/27). No cases of bile leak or ductal injury were reported. Rates of bile leak, post-operative complications and ERCP were lower following LLC compared to the group where LLC was not attempted (p < 0.01). CONCLUSION: LLC is a safe salvage technique and should be considered in cases where the critical view of safety cannot be established. The technique achieves cystic duct control in the majority of cases and favourable outcomes in the face of a difficult cholecystectomy.

Human monocytes store and secrete preformed CCL5, independent of de novo protein synthesis.

Monocytes are a subset of circulating peripheral blood mononuclear cells with diverse roles in immunity, including sentinel roles in cytokine secretion. Conventionally, cytokines require an inductive stimulus for their expression and secretion, resulting in a time lag from the time of stimulation to when the proteins are packaged and secreted. Because cytokines are the main communicators in the immune system, their temporal expression is a key factor in coordinating responses to efficiently resolve infection. Herein, we identify that circulating human monocytes contain preformed cytokines that are stored intracellularly, in both resting and activated states. Having preformed cytokines bypasses the time lag associated with de novo synthesis, allowing monocytes to secrete immune mediators immediately upon activation or sensing of microbe-associated molecular patterns. We demonstrate here that, out of several cytokines evaluated, human monocytes contain a previously undescribed reservoir of the preformed chemokine CCL5. Furthermore, we showed that CCL5 could be secreted from monocytes treated with the protein synthesis inhibitor (cycloheximide) and Golgi blocker (brefeldin A). We examined the possibility for uptake of extracellular CCL5 from platelet aggregates and observed no significant levels of platelet binding to our enriched monocyte preparations, indicating that the source of preformed CCL5 was not from platelets. Preformed CCL5 was observed to be distributed throughout the cytoplasm and partially colocalized with CD63+ and Rab11A+ membranes, implicating endosomal compartments in the intracellular storage and trafficking of CCL5.

A comparison of transhepatic versus transperitoneal cholecystostomy for acute calculous cholecystitis: a 5-year experience.

Percutaneous cholecystostomy is a treatment for acute calculous cholecystitis used in patients where surgery is high risk or challenging either to allow for surgical optimisation or as definitive treatment. In this case series we compare the outcomes of a transhepatic versus transperitoneal approach in patients undergoing percutaneous cholecystostomy for acute calculous cholecystitis. A retrospective review of patients from 2014 to 2019 was conducted and included demographics, percutaneous cholecystostomy route, complications and outcome. Fifty-one patients were included. Percutaneous cholecystostomy was placed transhepatically in 15 cases; transperitoneal in 30 cases; 6 cases had undetermined route. The transhepatic cohort had 43.5% fewer readmissions due to biliary sepsis, 32.5% fewer drain-related complications, and were less likely to require further treatment (32.5% reduction) compared to the transperitoneal cohort. In our experience, the transhepatic route is preferred due to fewer complications, fewer readmissions and a reduction in the need for further treatment.

Neurological Complications of Acute Rhinosinusitis: Meningitis.

Meningitis remains a rare but potentially life-threatening intracranial complication of acute rhinosinusitis. We describe a case of a 62-year-old man with a background of chronic rhinosinusitis who presented to hospital with confusion, fever and bilateral green purulent rhinorrhoea. After immediate sepsis management, urgent contrast-enhanced computed tomography head revealed opacification of all paranasal sinuses and bony erosion of the lateral walls of both ethmoid sinuses. He was treated with intravenous antibiotics, topical nasal steroids, decongestants and irrigation. Following a turbid lumbar puncture and multidisciplinary discussion, he was admitted to the critical care unit and later intubated due to further neurological deterioration. After 13 days admission and rehabilitation in the community he made a good recovery. This case highlights the importance of timely diagnosis and appropriate management of acute rhinosinusitis and awareness of the possible complications. Joint care with physicians and intensivists is crucial in the management of these sick patients.

Use of open source monitoring hardware to improve the production of MOFs: using STA-16(Ni) as a case study.

Affordable and readily available microelectronics are becoming prevalent in teaching laboratories however these useful and economic tools are not used widely in either academia or industry. Herein we report how a metal organic framework (MOF) synthetic route can be optimized using an in situ monitoring apparatus designed in-house on open source hardware for under $100. We demonstrate that the MOF can be produced at atmospheric pressure, an improvement over previous reports, but also with a reduction in reaction time of 93%. This improvement in reaction time was predicted after a single experiment using the monitoring kit showing how efficiencies in the lab can be gained with very little experimental and monetary overhead while minimising the resources used.

Diaphragm disease of the terminal ileum presenting as acute small bowel obstruction.

Diaphragm disease (DD) of the small bowel is a rarely reported complication of non-steroidal anti-inflammatory drug (NSAID) use, characterised by diaphragm-like strictures, most commonly in the ileum, causing varying degrees of obstruction. It typically presents in the elderly, over many years with non-specific symptoms. Diagnosis is challenging, the majority of cases relying on histopathology for confirmation. Treatment involves NSAID cessation and surgery through a combination of stricturoplasties and/or segmental resection. Very rarely DD presents as a surgical emergency. A case presenting as acute small bowel obstruction (SBO) is described, initially diagnosed as adhesions, later confirmed to be DD of the terminal ileum following histopathological examination. Given the widespread use of NSAIDs and an ageing population, it is likely the incidence of DD will increase. It is, therefore, important that surgeons are aware of this disease entity and consider it as a potential diagnosis in patients presenting with acute SBO.

Nodular fasciitis of the parotid gland engulfing the facial nerve: a conservative approach.

Nodular fasciitis (NF) is a rapidly growing benign lesion rarely reported in the parotid gland. It shares cytological features with other benign and malignant parotid neoplasms and may be difficult to diagnose based on fine needle aspiration cytology alone. Given this diagnostic conundrum, surgical excision for histology is recommended to facilitate definitive diagnosis. A case with significant involvement of the facial nerve is described, which has not previously been reported in the literature. Despite features of potential malignancy, the decision was taken to biopsy the lesion and not proceed to complete excision in an attempt to reduce the risk of facial nerve injury. Expert opinion later diagnosed NF. Contrary to accepted practice, where diagnostic uncertainty remains around the malignant potential of a lesion, risks and benefits of complete excision versus a conservative approach should be carefully weighed especially when the facial nerve is involved and NF is a possible diagnosis.

Feasibility of measuring zinc in human nails using portable x-ray fluorescence.

A variety of adverse health effects have been identified as resulting from zinc deficiency. Zinc supplementation may therefore be indicated for certain individuals or populations. A rapid and straightforward means of assessing zinc status in humans would be of considerable medical benefit. In this study, the feasibility of measuring zinc levels in human fingernails or toenails using a portable x-ray fluorescence technique was assessed. Whole nail models (or phantoms) were constructed from resin, and dosed with various concentrations of zinc. These different concentration "nails" were cut into small slices of 4.4 ±â€¯0.2 mm width. The combination of these various slices into different arrangements allowed the modeling of different time-dependent zinc exposure scenarios. A portable x-ray fluorescence device was tested using an "open beam" configuration having a beam diameter of ∼9 mm, and using a "weld mask" configuration with the beam width reduced to 2.9 mm. Minimum detection limits were determined to be 0.15 ±â€¯0.01 ppm for the open beam, and 1.13 ±â€¯0.08 ppm when using the weld mask. By scanning across the length of the model nails, it was demonstrated that differences in zinc levels deposited over time could be detected, and that the weld mask configuration was better suited to resolving spatial changes. The x-ray fluorescence approach was found to be highly sensitive for detecting zinc in nail, and capable of differentiating patterns of zinc uptake over time.

What are the Conditions of Riparian Ecosystems? Identifying Impaired Floodplain Ecosystems across the Western U.S. Using the Riparian Condition Assessment (RCA) Tool.

Environmental stressors associated with human land and water-use activities have degraded many riparian ecosystems across the western United States. These stressors include (i) the widespread expansion of invasive plant species that displace native vegetation and exacerbate streamflow and sediment regime alteration; (ii) agricultural and urban development in valley bottoms that decouple streams and rivers from their floodplains and reduce instream wood recruitment and retention; and (iii) flow modification that reduces water quantity and quality, degrading aquatic habitats. Here we apply a novel drainage network model to assess the impacts of multiple stressors on reach-scale riparian condition across two large U.S. regions. In this application, we performed a riparian condition assessment evaluating three dominant stressors: (1) riparian vegetation departure from historical condition; (2) land-use intensity within valley bottoms; and (3) floodplain fragmentation caused by infrastructure within valley bottoms, combining these stressors in a fuzzy inference system. We used freely available, geospatial data to estimate reach-scale (500 m) riparian condition for 52,800 km of perennial streams and rivers, 25,600 km in Utah, and 27,200 km in 12 watersheds of the interior Columbia River Basin (CRB). Model outputs showed that riparian condition has been at least moderately impaired across ≈70% of the streams and rivers in Utah and ≈49% in the CRB. We found 84% agreement (Cohen's ĸ = 0.79) between modeled reaches and field plots, indicating that modeled riparian condition reasonably approximates on-the-ground conditions. Our approach to assessing riparian condition can be used to prioritize watershed-scale floodplain conservation and restoration by providing network-scale data on the extent and severity of riparian degradation. The approach that we applied here is flexible and can be expanded to run with additional riparian stressor data and/or finer resolution input data.

Detection of lead in bone phantoms and arsenic in soft tissue phantoms using synchrotron radiation and a portable x-ray fluorescence system.

The differences and commonalities between x-ray fluorescence results obtained using synchrotron radiation and a portable x-ray fluorescence device were examined using arsenic in soft tissue phantoms and lead in bone phantoms. A monochromatic beam energy of 15.8 keV was used with the synchrotron, while the portable device employed a rhodium anode x-ray tube operated at 40 kV. Bone phantoms, dosed with varying quantities of lead, were made of Plaster of Paris and placed underneath skin phantoms of either 3.1 mm or 3.9 mm thickness. These skin phantoms were constructed from polyester resin, and dosed with varying amounts of arsenic. Using an irradiation time of 120 s, arsenic Kα and Kß, and lead Lα and Lß characteristic x-ray peaks were analysed. This information was used to calculate calibration line slopes and minimum detection limits for each data set. As expected, minimum detection limits were much lower at the synchrotron for detecting arsenic and lead. Both approaches produced lower detection limits for arsenic in soft tissue than for lead in bone when simultaneous detection was attempted. Although arsenic Kα and lead Lα emissions share similar energies, it was possible to detect both elements in isolation by using the arsenic Kß and lead Lß characteristic x-rays. Greater thickness of soft tissue phantom reduced the ability to detect the underlying lead. Experiments with synchrotron radiation could help guide future efforts toward optimizing a portable x-ray fluorescence in vivo measurement device.

Structural Descriptors of Zeolitic-Imidazolate Frameworks Are Keys to the Activity of Fe-N-C Catalysts.

Active and inexpensive catalysts for oxygen reduction are crucially needed for the widespread development of polymer electrolyte fuel cells and metal-air batteries. While iron-nitrogen-carbon materials pyrolytically prepared from ZIF-8, a specific zeolitic imidazolate framework (ZIF) with sodalite topology, have shown enhanced activities toward oxygen reduction in acidic electrolyte, the rational design of sacrificial metal-organic frameworks toward this application has hitherto remained elusive. Here, we report for the first time that the oxygen reduction activity of Fe-N-C catalysts positively correlates with the cavity size and mass-specific pore volume in pristine ZIFs. The high activity of Fe-N-C materials prepared from ZIF-8 could be rationalized, and another ZIF structure leading to even higher activity was identified. In contrast, the ORR activity is mostly unaffected by the ligand chemistry in pristine ZIFs. These structure-property relationships will help identifying novel sacrificial ZIF or porous metal-organic frameworks leading to even more active Fe-N-C catalysts. The findings are of great interest for a broader application of the class of inexpensive metal-nitrogen-carbon catalysts that have shown promising activity also for the hydrogen evolution (Co-N-C) and carbon dioxide reduction (Fe-N-C and Mn-N-C).

Riparian vegetation as an indicator of riparian condition: Detecting departures from historic condition across the North American West.

Floodplain riparian ecosystems support unique vegetation communities and high biodiversity relative to terrestrial landscapes. Accordingly, estimating riparian ecosystem health across landscapes is critical for sustainable river management. However, methods that identify local riparian vegetation condition, an effective proxy for riparian health, have not been applied across broad, regional extents. Here we present an index to assess reach-scale (500 m segment) riparian vegetation condition across entire drainage networks within large, physiographically-diverse regions. We estimated riparian vegetation condition for 53,250 km of perennial streams and rivers, 25,685 km in Utah, and 27,565 km in twelve watersheds of the interior Columbia River Basin (CRB), USA. We used nationally available, existing land cover classification derived from 30 m Landsat imagery (LANDFIRE EVT) and a modeled estimate of pre-European settlement land cover (LANDFIRE BpS). The index characterizes riparian vegetation condition as the ratio of existing native riparian vegetation cover to pre-European settlement riparian vegetation cover at a given reach. Roughly 62% of Utah and 48% of CRB watersheds showed significant (>33%) to large (>66%) departure from historic condition. Riparian vegetation change was predominantly caused by human land-use impacts (development and agriculture), or vegetation change (native riparian to invasive or upland vegetation types) that likely resulted from flow and disturbance regime alteration. Through comparisons to ground-based classification results, we estimate the existing vegetation component of the index to be 85% accurate. Our assessments yielded riparian condition maps that will help resource managers better prioritize sites and treatments for reach-scale conservation and restoration activities.

Rickettsial Infections among Ctenocephalides felis and Host Animals during a Flea-Borne Rickettsioses Outbreak in Orange County, California.

Due to a resurgence of flea-borne rickettsioses in Orange County, California, we investigated the etiologies of rickettsial infections of Ctenocephalides felis, the predominant fleas species obtained from opossums (Didelphis virginiana) and domestic cats (Felis catus), collected from case exposure sites and other areas in Orange County. In addition, we assessed the prevalence of IgG antibodies against spotted fever group (SFGR) and typhus group (TGR) rickettsiae in opossum sera. Of the 597 flea specimens collected from opossums and cats, 37.2% tested positive for Rickettsia. PCR and sequencing of rickettsial genes obtained from C. felis flea DNA preparations revealed the presence of R. typhi (1.3%), R. felis (28.0%) and R. felis-like organisms (7.5%). Sera from opossums contained TGR-specific (40.84%), but not SFGR-specific antibodies. The detection of R. felis and R. typhi in the C. felis fleas in Orange County highlights the potential risk for human infection with either of these pathogens, and underscores the need for further investigations incorporating specimens from humans, animal hosts, and invertebrate vectors in endemic areas. Such studies will be essential for establishing a link in the ongoing flea-borne rickettsioses outbreaks.

Using multiscale spatial models to assess potential surrogate habitat for an imperiled reptile.

UNLABELLED: In evaluating conservation and management options for species, practitioners might consider surrogate habitats at multiple scales when estimating available habitat or modeling species' potential distributions based on suitable habitats, especially when native environments are rare. Species' dependence on surrogates likely increases as optimal habitat is degraded and lost due to anthropogenic landscape change, and thus surrogate habitats may be vital for an imperiled species' survival in highly modified landscapes. We used spatial habitat models to examine a potential surrogate habitat for an imperiled ambush predator (eastern diamondback rattlesnake, Crotalus adamanteus; EDB) at two scales. The EDB is an apex predator indigenous to imperiled longleaf pine ecosystems (Pinus palustris) of the southeastern United States. Loss of native open-canopy pine savannas and woodlands has been suggested as the principal cause of the species' extensive decline. We examined EDB habitat selection in the Coastal Plain tidewater region to evaluate the role of marsh as a potential surrogate habitat and to further quantify the species' habitat requirements at two scales: home range (HR) and within the home range (WHR). We studied EDBs using radiotelemetry and employed an information-theoretic approach and logistic regression to model habitat selection as use vs. AVAILABILITY: We failed to detect a positive association with marsh as a surrogate habitat at the HR scale; rather, EDBs exhibited significantly negative associations with all landscape patches except pine savanna. Within home range selection was characterized by a negative association with forest and a positive association with ground cover, which suggests that EDBs may use surrogate habitats of similar structure, including marsh, within their home ranges. While our HR analysis did not support tidal marsh as a surrogate habitat, marsh may still provide resources for EDBs at smaller scales.

Epizootiology of Tacaribe serocomplex viruses (Arenaviridae) associated with neotomine rodents (Cricetidae, Neotominae) in southern California.

The objective of this study was to advance our knowledge of the epizootiology of Bear Canyon virus and other Tacaribe serocomplex viruses (Arenaviridae) associated with wild rodents in California. Antibody (immunoglobulin G [IgG]) to a Tacaribe serocomplex virus was found in 145 (3.6%) of 3977 neotomine rodents (Cricetidae: Neotominae) captured in six counties in southern California. The majority (122 or 84.1%) of the 145 antibody-positive rodents were big-eared woodrats (Neotoma macrotis) or California mice (Peromyscus californicus). The 23 other antibody-positive rodents included a white-throated woodrat (N. albigula), desert woodrat (N. lepida), Bryant's woodrats (N. bryanti), brush mice (P. boylii), cactus mice (P. eremicus), and deer mice (P. maniculatus). Analyses of viral nucleocapsid protein gene sequence data indicated that Bear Canyon virus is associated with N. macrotis and/or P. californicus in Santa Barbara County, Los Angeles County, Orange County, and western Riverside County. Together, analyses of field data and antibody prevalence data indicated that N. macrotis is the principal host of Bear Canyon virus. Last, the analyses of viral nucleocapsid protein gene sequence data suggested that the Tacaribe serocomplex virus associated with N. albigula and N. lepida in eastern Riverside County represents a novel species (tentatively named "Palo Verde virus") in the genus Arenavirus.

Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear phenotype.

Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2(-n/X) and the arterial area ratio ß = 2(1-2/X). Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, ß > 1) to a high-shear stress phenotype (X < 2, ß < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process.

Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease: evidence for enhanced Anrep effect.

Patients with pulmonary hypertension associated with congenital heart disease survive longer with preserved right ventricular (RV) function compared with those with primary pulmonary hypertension. The purpose of this study was to test the hypothesis that superior RV performance can be demonstrated, at baseline and when challenged with increased RV afterload, in lambs with chronic left-to-right cardiac shunts compared with control lambs. A shunt was placed between the pulmonary artery and the aorta in fetal lambs (shunt). RV pressure-volume loops were obtained 4 wk after delivery in shunt and control lambs, before and after increased afterload was applied using pulmonary artery banding (PAB). Baseline stroke volume (8.7 ± 1.8 vs. 15.8 ± 2.7 ml, P = 0.04) and cardiac index (73.0 ± 4.0 vs. 159.2 ± 25.1 ml·min(-1)·kg(-1), P = 0.02) were greater in shunts. After PAB, there was no difference in the change in cardiac index (relative to baseline) between groups; however, heart rate (HR) was greater in controls (168 ± 7.3 vs. 138 ± 6.6 beats/min, P = 0.01), and end-systolic elastance (Ees) was greater in shunts (2.63 vs. 1.31 × baseline, P = 0.02). Control lambs showed decreased mechanical efficiency (71% baseline) compared with shunts. With acute afterload challenge, both controls and shunts maintained cardiac output; however, this was via maladaptive responses in controls, while shunts maintained mechanical efficiency and increased contractility via a proposed enhanced Anrep effect-the second, slow inotropic response in the biphasic ventricular response to increased afterload, a novel finding in the RV. The mechanisms related to these physiological differences may have important therapeutic implications.

Altered reactivity and nitric oxide signaling in the isolated thoracic duct from an ovine model of congenital heart disease with increased pulmonary blood flow.

We have previously shown decreased pulmonary lymph flow in our lamb model of chronically increased pulmonary blood flow, created by the in utero placement of an 8-mm aortopulmonary shunt. The purpose of this study was to test the hypothesis that abnormal lymphatic function in shunt lambs is due to impaired lymphatic endothelial nitric oxide (NO)-cGMP signaling resulting in increased lymphatic vascular constriction and/or impaired relaxation. Thoracic duct rings were isolated from 4-wk-old shunt (n = 7) and normal (n = 7) lambs to determine length-tension properties, vascular reactivity, and endothelial NO synthase protein. At baseline, shunt thoracic duct rings had 2.6-fold higher peak to peak tension and a 2-fold increase in the strength of contractions compared with normal rings (P < 0.05). In response to norepinephrine, shunt thoracic duct rings had a 2.4-fold increase in vascular tone compared with normal rings (P < 0.05) and impaired relaxation in response to the endothelium-dependent dilator acetylcholine (63% vs. 13%, P < 0.05). In vivo, inhaled NO (40 ppm) increased pulmonary lymph flow (normalized for resistance) ∼1.5-fold in both normal and shunt lambs (P < 0.05). Inhaled NO exposure increased bioavailable NO [nitrite/nitrate (NOx); ∼2.5-fold in normal lambs and ∼3.4-fold in shunt lambs] and cGMP (∼2.5-fold in both) in the pulmonary lymph effluent (P < 0.05). Chronic exposure to increased pulmonary blood flow is associated with pulmonary lymphatic endothelial injury that disrupts NO-cGMP signaling, leading to increased resting vasoconstriction, increased maximal strength of contraction, and impaired endothelium-dependent relaxation. Inhaled NO increases pulmonary lymph NOx and cGMP levels and pulmonary lymph flow in normal and shunt lambs. Therapies that augment NO-cGMP signaling within the lymphatic system may provide benefits, warranting further study.

Stem cell antigen-1 in skeletal muscle function.

Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca-1 is expressed on muscle-derived stem cells and myogenic precursors recruited to sites of muscle injury. We previously reported that inhibition of Sca-1 expression stimulated myoblast proliferation in vitro and regulated the tempo of muscle repair in vivo. Despite its function in myoblast expansion during muscle repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and hindlimb muscles to elucidate the tissue, contractile, and functional effects of Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber cross-sectional area, and Pax7+ myoblast number showed little differences between ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in KO versus WT mice, with young KO mice achieving results similar to aging WT animals. In addition, KO mice did not improve with practice, while WT animals demonstrated conditioning over time. Surprisingly, myomechanical analysis of isolated muscles showed that KO young muscle generated more force and experienced less fatigue. However, KO muscle also demonstrated incomplete relaxation with fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning with exercise, and that deficient conditioning in Sca-1 KO animals becomes more pronounced with age.