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Following two centuries of research at Karnak, our understanding of the origins and development of this famous ancient Egyptian temple complex remains limited. Recent archaeological excavation in the Ptah temple, however, has reached its earliest levels, providing a first, securely dated stratigraphic sequence. Despite flood risks, the development of the religious complex c. 2200-2000 BC was made possible by the retreating Nile riverbank. Thus, the river and the expanding Karnak temple complex played major roles in the takeover of Egypt by the Eleventh Dynasty rulers and the growth of the new capital at Thebes, a potent combination of forces-fluvial, religious and secular--encountered among other early state powers. Keywords: First Intermediate Period, Thebes, Amun temple, settlement, landscape evolution, Introduction Geoarchaeological research conducted on cities situated on alluvial plains has long demonstrated the significant impact of river movement on urban development and landscape change though time (e.g. Mackay 1945; [...]

After the sharp transition to aridity that followed the "Green Sahara" episode 5500 years ago, human settlements took refuge in Egyptian oases, which have to varying extents been "Green Oases" for centuries. In that period, synchronous with the beginning of historical times, the desert's aridity is generally regarded as broadly comparable to the current period. Natural and anthropogenic deposits studied during 13 excavation campaigns in Bahariya Oasis (Egyptian Desert) suggest that a fairly clear transition from a relatively green environment to much more arid landscapes occurred in the first millennia BCE and CE. This article aims at establishing the chronology of human occupations and environmental change within this period, by combining archaeological and radiocarbon data, using Bayesian modeling. It reveals that the drying up of the environment experienced by desert farmers occurred at some point between the reigns of Antoninus Pius and Caracalla (2nd–3rd century CE). The accuracy of the produced chronological models made it possible to highlight synchronisms between the end of this "Green Oasis" phase and comparable aridification phenomena on regional and interregional scales. Similar degradation processes on remote sites inside the Roman Empire might be explained by globalized anthropogenic agencies overlapping with a broader climatic drying. [ABSTRACT FROM AUTHOR]

The British Museum Asyut Region Project aims at reconstructing and preserving the deep history of the Asyut region through survey and documentation of its pharaonic and post-pharaonic heritage, including the varied responses of local communities who live atop the layers of history below. Two initial field seasons have concentrated on the modern village of Shutb, 5 km south of Asyut, which is believed to perch on top of the remains of ancient Shashotep. Documentation of (part of) the tell and an augering survey in its immediate surroundings confirm the presence of ancient remains underneath the modern village. Engagement with the most recent layers of history includes the documentation of Shutb's outstanding vernacular architecture and capacity building and awareness sessions with local stakeholders. [ABSTRACT FROM AUTHOR]

Background: The complexity of the skeletal muscle and the identification of numerous human disease-causing mutations in its constitutive proteins make it an interesting tissue for proteomic studies aimed at understanding functional relationships of interacting proteins in both health and diseases. Method: We undertook a large-scale study using two-hybrid screens and a human skeletal-muscle cDNA library to establish a proteome-scale map of protein-protein interactions centered on proteins involved in limb-girdle muscular dystrophies (LGMD). LGMD is a group of more than 20 different neuromuscular disorders that principally affect the proximal pelvic and shoulder girdle muscles. Results and conclusion: The interaction network we unraveled incorporates 1018 proteins connected by 1492 direct binary interactions and includes 1420 novel protein-protein interactions. Computational, experimental and literature-based analyses were performed to assess the overall quality of this network. Interestingly, LGMD proteins were shown to be highly interconnected, in particular indirectly through sarcomeric proteins. In-depth mining of the LGMD-centered interactome identified new candidate genes for orphan LGMDs and other neuromuscular disorders. The data also suggest the existence of functional links between LGMD2B/dysferlin and gene regulation, between LGMD2C/?-sarcoglycan and energy control and between LGMD2G/telethonin and maintenance of genome integrity. This dataset represents a valuable resource for future functional investigations. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major risk factor for cardiovascular morbidity and mortality. Despite this fact and the development of efective antihypertensive drug therapy, hypertension is often poorly controlled. Community pharmacies are an ideal site for the management of hypertension and other modifiable cardiovascular risk factors. The purpose of the current study was to develop and assess a pharmacy-based cardiovascular risk screening program implemented by graduate students. Methods: Four graduate students trained as health coaches screened a convenience sample of adults who were interested in cardiovascular risk assessment in 21 Montreal area pharmacies. On the screening day, we assessed cardiovascular risk factors, including blood pressure, used the Cardiovascular Life Expectancy Model, which includes cardiovascular age, to inform patients of their personalized risk profile, delivered an individualized health coaching intervention and conducted a participant satisfaction survey. This was followed by an individualized health coaching intervention. The intervention program was implemented by trained graduate students and supported by pharmacists. Results: Among the 238 patients who participated (57% female, mean age 60.6 years), 67% had a body mass index (BMI) greater than 25 kg/m2, 52% had abdominal obesity, 58% reported insufficient physical activity and 14% were smokers. A total of 120 patients (51%) were taking antihypertensive medication, yet 63 (53%) had blood pressure readings above currently accepted targets. Higher BMI and physical inactivity were associated with increased rates of poorly controlled hypertension. Conclusion: The screening program identified individuals with modifiable cardiovascular risk factors and poorly controlled hypertension. The intervention program was well received by participants and the majority provided contact information for future cardiovascular screening clinics. These findings support the feasibility of screening programs run by graduate students in the pharmacy setting. [ABSTRACT FROM AUTHOR]

Objective: The giant protein titin is essential for striated muscle development, structure, and elasticity. All titin mutations reported to date cause late-onset, dominant disorders involving either skeletal muscle or the heart. Our aim was to delineate the phenotype and determine the genetic defects in two consanguineous families with an early-onset, recessive muscle and cardiac disorder.Methods: Clinical and myopathological reevaluation of the five affected children, positional cloning, immunofluorescence, and Western blot studies were performed.Results: All children presented with congenital muscle weakness and childhood-onset fatal dilated cardiomyopathy. Skeletal muscle biopsies showed minicores, centrally located nuclei, and/or dystrophic lesions. In each family, we identified a homozygous titin deletion in exons encoding the C-terminal M-line region. Both deletions cause a frameshift downstream of the titin kinase domain and protein truncation. Immunofluorescence confirmed that truncated titins lacking the C-terminal end were incorporated into sarcomeres. Calpain 3 was secondarily depleted.Interpretation: M-line titin homozygous truncations cause the first congenital and purely recessive titinopathy, and the first to involve both cardiac and skeletal muscle. These results expand the spectrum of early-onset myopathies and suggest that titin segments downstream of the kinase domain are dispensable for skeletal and cardiac muscle development, but are crucial for maintaining sarcomere integrity. [ABSTRACT FROM AUTHOR]

Studies calpain 33 mRNA expression in mice after denervation and during muscle regeneration. Changes in callpain 3 and alpha-skeletal actin mRNA levels; Quantification of specific mRNA; Apoptosis in denervated muscles.

The limb-girdle muscular dystrophies are a genetically heterogeneous group of inherited progressive muscle disorders that affect mainly the proximal musculature, with evidence for at least three autosomal dominant and eight autosomal recessive loci. The latter mostly involve mutations in genes encoding components of the dystrophin-associated complex; another form is caused by mutations in the gene for the muscle-specific protease calpain 3. Using a positional cloning approach, we have identified the gene for a form of limb-girdle muscular dystrophy that we previously mapped to chromosome 2p13 (LGMD2B). This gene shows no homology to any known mammalian gene, but its predicted product is related to the C. elegans spermatogenesis factor fer-1. We have identified two homozygous frameshift mutations in this gene, resulting in muscular dystrophy of either proximal or distal onset in nine families. The proposed name `dysferlin' combines the role of the gene in producing muscular dystrophy with its C. elegans homology. [ABSTRACT FROM AUTHOR]

Introduction. A fall may impact a person’s physical, emotional, and psychological well-being. Fall prevention programs are being implemented to reduce these negative outcomes. However, linguistic barriers in health services may reduce access to such prevention programs. A telehealth fall prevention program was designed to increase access to such programs in French for Francophone minority communities in Canada. This capacity-building project aimed to support community partners to deliver this telehealth program and document strategies used to reach, adopt, and implement the program within various Francophone and Acadian Minority Communities. Methods. A sequential explanatory mixed methodology was used to document reach, adoption, and implementation strategies and describe the lived experiences of program facilitators and organization representatives. Reach, adoption, and implementation were documented and analyzed descriptively, while lived experiences were analyzed using content analysis following the Consortium Framework for Implementation Research. Results. Twelve organization representatives or program facilitators from eight organizations operating in four different provinces participated in the study. Three themes emerged from the qualitative data on reach and adoption: external context, internal context, and capacity building. Four themes were identified as barriers and facilitators to implementation: level of preparation and time management, interpersonal relations and telepresence, exercise facilitation and safety, and technological problem-solving. Conclusion. Using tailored reach and adoption strategies such as prioritizing provinces with higher proportions of needs and training local community program facilitators may lead to the successful implementation of a new telehealth fall prevention program. Results from this study could potentially inform other primary prevention programs or telehealth program implementation. [ABSTRACT FROM AUTHOR]

Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs with the same steroids. Conclusion Several particulate steroids have an immediate and massive effect on microvascular perfusion because of formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs. (©) RSNA, 2016 Online supplemental material is available for this article.

Mutations in dysferlin and anoctamin 5 are the cause of muscular disorders, with the main presentations as limb-girdle muscular dystrophy or Miyoshi type of distal myopathy. Both these proteins have been implicated in sarcolemmal resealing. On the basis of similarities in associated phenotypes and protein functions, we tested the hypothesis that ANO5 protein could compensate for dysferlin absence. We first defined that the main transcript of ANO5 expressed in skeletal muscle is the 22-exon full-length isoform, and we demonstrated that dysferlin-deficient (Dysf (prmd)) mice have lower Ano5 expression levels, an observation that further enhanced the rational of the tested hypothesis. We then showed that AAV-mediated transfer of human ANO5 (hANO5) did not lead to apparent toxicity in wild-type mice. Finally, we demonstrated that AAV-hANO5 injection was not able to compensate for dysferlin deficiency in the Dysf (prmd) mouse model or improve the membrane repair defect seen in the absence of dysferlin. Consequently, overexpressing hANO5 does not seem to provide a valuable therapeutic strategy for dysferlin deficiency.

We report a Belgian family with autosomal dominant, late-onset, distal myopathy with selective foot extensor muscle involvement of the lower legs. Linkage to the tibial muscular dystrophy (TMD) locus 2q31 was not evident at first because of incomplete disease penetrance in a 50-year-old asymptomatic family member. An abnormal tibialis anterior muscle biopsy established her subclinical status and linkage of the family to the TMD locus. Mutation analysis showed a disease-specific, heterozygous point mutation in the last exon, Mex6, of the titin gene. This is the third mutation found in TMD and the second European family with TMD outside the Finnish population, suggesting that titinopathies may occur in various populations.