Medical Care of Adults With Down Syndrome: A Clinical Guideline.

Importance: Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. Objective: To develop an evidence-based clinical practice guideline for adults with Down syndrome. Evidence Review: The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence. Findings: From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome. Conclusions and Relevance: These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.

Benefits and Harms of Mammography Screening for Women With Down Syndrome: a Collaborative Modeling Study.

BACKGROUND: Women with Down syndrome have a lower breast cancer risk and significantly lower life expectancies than women without Down syndrome. Therefore, it is not clear whether mammography screening strategies used for women without Down syndrome would benefit women with Down syndrome in the same way. OBJECTIVE: To determine the benefits and harms of various mammography screening strategies for women with Down syndrome using collaborative simulation modeling. DESIGN: Two established Cancer Intervention and Surveillance Modeling Network (CISNET) simulation models estimated the benefits and harms of various screening strategies for women with Down syndrome over a lifetime horizon. PARTICIPANTS: We modeled a hypothetical cohort of US women with Down syndrome who were born in 1970. INTERVENTIONS: Annual, biennial, triennial, and one-time digital mammography screenings during the ages 40-74. MAIN MEASURES: The models estimated numbers of mammograms, false-positives, benign biopsies, breast cancer deaths prevented, and life-years gained per 1000 screened women when compared with no screening. KEY RESULTS: In average-risk women 50-74, biennial screening incurred 122 mammograms, 10 false-positive mammograms, and 1.4 benign biopsies per one life-year gained compared with no screening. In women with Down syndrome, the same screening strategy incurred 2752 mammograms, 242 false-positive mammograms, and 34 benign biopsies per one life-year gained compared with no screening. The harm/benefit ratio varied for other screening strategies, and was most favorable for one-time screening at age 50, which incurred 1629 mammograms, 144 false-positive mammograms, and 20 benign biopsies per one life-year gained compared with no screening. CONCLUSIONS: The harm/benefit ratios for various mammography screening strategies in women with Down syndrome are not as favorable as those for average-risk women. The benefit of screening mammography for women with Down syndrome is less pronounced due to lower breast cancer risk and shorter life expectancy.

The science of food security.

We need to feed an estimated population in excess of 9 billion by 2050 with diminishing natural resources, whilst ensuring the health of people and the planet. Herein we connect the future global food demand to the role of agricultural and food science in producing and stabilising foods to meet the global food demand. We highlight the challenges to food and agriculture systems in the face of climate change and global megatrends that are shaping the future world. We discuss the opportunities to reduce food loss and waste, and recover produce that is currently wasted to make this the new raw ingredient supply for the food industry. Our systems-based perspective links food security to agricultural productivity, food safety, health and nutrition, processing and supply chain efficiency in the face of global and industry megatrends. We call for a collaborative, transdisciplinary approach to the science of food security, with a focus on enabling technologies within a context of social, market and global trends to achieve food and nutritional security.

Co-occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines.

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. The United States Preventive Service Task Force (USPSTF) has developed criteria for prioritizing conditions of public health importance with the potential for providing screening recommendations to improve clinical care. The quality of existing evidence needed to inform clinical guidelines has not been previously reviewed. Using the National Library of Medicine (NLM) database PubMed, we first identified 18 peer reviewed articles that addressed co-occurring medical conditions in adults with DS. Those conditions discussed in over half of the articles were prioritized for further review. Second, we performed detailed literature searches on these specific conditions. To inform the search strategy and review process a series of key questions were formulated a priori. The quality of available evidence was then graded and knowledge gaps were identified. The number of participating adults and the design of clinical studies varied by condition and were often inadequate for answering all of our key questions. We provide data on thyroid disease, cervical spine disease, hearing impairment, overweight-obesity, sleep apnea, congenital heart disease, and osteopenia-osteoporosis. Minimal evidence demonstrates massive gaps in our clinical knowledge that compromises clinical decision-making and management of these medically complex individuals. The development of evidence-based clinical guidance will require an expanded clinical knowledge-base in order to move forward.

MATRILINEAL, a sperm-specific phospholipase, triggers maize haploid induction.

Sexual reproduction in flowering plants involves double fertilization, the union of two sperm from pollen with two sex cells in the female embryo sac. Modern plant breeders increasingly seek to circumvent this process to produce doubled haploid individuals, which derive from the chromosome-doubled cells of the haploid gametophyte. Doubled haploid production fixes recombinant haploid genomes in inbred lines, shaving years off the breeding process. Costly, genotype-dependent tissue culture methods are used in many crops, while seed-based in vivo doubled haploid systems are rare in nature and difficult to manage in breeding programmes. The multi-billion-dollar maize hybrid seed business, however, is supported by industrial doubled haploid pipelines using intraspecific crosses to in vivo haploid inducer males derived from Stock 6, first reported in 1959 (ref. 5), followed by colchicine treatment. Despite decades of use, the mode of action remains controversial. Here we establish, through fine mapping, genome sequencing, genetic complementation, and gene editing, that haploid induction in maize (Zea mays) is triggered by a frame-shift mutation in MATRILINEAL (MTL), a pollen-specific phospholipase, and that novel edits in MTL lead to a 6.7% haploid induction rate (the percentage of haploid progeny versus total progeny). Wild-type MTL protein localizes exclusively to sperm cytoplasm, and pollen RNA-sequence profiling identifies a suite of pollen-specific genes overexpressed during haploid induction, some of which may mediate the formation of haploid seed. These findings highlight the importance of male gamete cytoplasmic components to reproductive success and male genome transmittance. Given the conservation of MTL in the cereals, this discovery may enable development of in vivo haploid induction systems to accelerate breeding in crop plants.

Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin ß.

Meprin metalloproteases play a role in the pathology of ischemia/reperfusion- (IR-) induced renal injury. The endoplasmic reticulum-associated protein, osteosarcoma-9 (OS-9), has been shown to interact with the carboxyl-terminal tail of meprin ß. More importantly, OS-9 interacts with the hypoxia inducible factor-1α (HIF-1α) and the prolyl-hydroxylase, proteins which mediate the cell's response to hypoxia. To determine if OS-9 is a meprin substrate, kidney proteins from meprin αß knockout mice (αßKO) (which lack endogenous meprins) and purified human OS-9 were incubated with activated forms of meprin A and meprin B, and Western blot analysis was used to evaluate proteolytic processing of OS-9. Fragmentation of OS-9 was observed in reactions with meprin B, but not meprin A. To determine whether meprin B cleaves OS-9 in vivo, wild-type (WT) and meprin αßKO mice were subjected to IR-induced renal injury. Fragmentation of OS-9 was observed in kidney proteins from WT mice subjected to IR, but not in meprin αßKO counterparts. Transfection of kidney cells (MDCK and HEK293) with meprin ß cDNA prevented accumulation of OS-9 following exposure to the hypoxia mimic, CoCl2. These data suggest that meprin ß interaction with OS-9 plays a role in the hypoxia response associated with IR-induced renal injury.

Maternal Haploids Are Preferentially Induced by CENH3-tailswap Transgenic Complementation in Maize.

Doubled haploid plants are invaluable breeding tools but many crop species are recalcitrant to available haploid induction techniques. To test if haploid inducer lines can be engineered into crops, CENH3 (-∕-) and CENH3:RNAi lines were complemented by AcGREEN-tailswap-CENH3 or AcGREEN-CENH3 transgenes. Haploid induction rates were determined following testcrosses to wild-type plants after independently controlling for inducer parent sex and transgene zygosity. CENH3 fusion proteins were localized to centromeres and did not cause vegetative defects or male sterility. CENH3:RNAi lines did not demonstrate consistent knockdown and rarely produced haploids. In contrast, many of the complemented CENH3 (-∕-) lines produced haploids at low frequencies. The rate of gynogenic haploid induction reached a maximum of 3.6% in several hemizygous individuals when backcrossed as males. These results demonstrate that CENH3-tailswap transgenes can be used to engineer in vivo haploid induction systems into maize plants.

Subtotal Nasal Reconstruction: Military-civilian Collaboration in Care of an Afghan-American Woman's Plight.

Military plastic surgeons perform reconstructive surgeries for various congenital, oncologic, and traumatic craniofacial injuries or deformities. Recently, our Walter Reed National Military Medical Center Plastic Surgery team was tasked to care for a woman who bravely sought a new and better life in the United States after she suffered amputation of her nose and bilateral ears while in her home country of Afghanistan. A military-civilian team collaborated throughout her reconstructive planning, treatment, and postoperative course to create both an aesthetically acceptable and functional subtotal nasal reconstruction. This case report details the patient's unique journey, her reconstructive course, and highlights her reintegration into a new life and society.

Delivery of electroconvulsive therapy in Canada: a first national survey report on usage, treatment practice, and facilities.

OBJECTIVES: The aims of this study were to document electroconvulsive therapy use in Canada with respect to treatment facilities and caseloads based on a survey of practice (Canadian Electroconvulsive Therapy Survey/Enquete Canadienne Sur Les Electrochocs-CANECTS/ECANEC) and to consider these findings in the context of guideline recommendations. METHOD: All 1273 registered hospitals in Canada were contacted, and 175 sites were identified as providing electroconvulsive therapy; these sites were invited to complete a comprehensive questionnaire. The survey period was calendar year 2006 or fiscal year 2006/2007. National usage rates were estimated from the responses. RESULTS: Sixty-one percent of the sites completed the questionnaire; a further 10% provided caseload data. Seventy were identified as general; 31, as university teaching; and 21, as provincial psychiatric/other single specialty (psychiatric) hospitals. Caseload volumes ranged from a mean of fewer than 2 to greater than 30 treatments per week. Estimated national usage during the 1-year survey period was 7340 to 8083 patients (2.32-2.56 per 10,000 population) and 66,791 to 67,424 treatments (2.11-2.13 per 1000 population). The diagnostic indications, admission status, and protocols for course end points are described. CONCLUSIONS: The usage rates are in keeping with earlier Canadian data and with those from other jurisdictions. The difficulty obtaining caseload data from individual hospitals is indicative of the need for standardized data collection to support both clinical research and quality assurance. The wide variation in protocols for number of treatments per course indicates a need for better informed clinical guidelines. The broad range of caseload volumes suggests the need to review the economies of scale in the field.

A decade of conflict: flap coverage options and outcomes in traumatic war-related extremity reconstruction.

BACKGROUND: War trauma patients who have sustained extremity trauma often exhibit extensive zones of injury with multiple concomitant injuries that can contribute to limited coverage options. Thus, flap availability and choice can become critical in the reconstruction algorithm of these severely traumatized patients. The authors' purpose was to analyze the outcomes of muscle and fasciocutaneous flaps during their extremity reconstructive experience to determine which option had better flap and limb salvage outcomes. METHODS: A retrospective review of servicemembers treated with flap-based limb salvage from 2003 through 2012 at the National Capital Consortium was completed. Patients were divided into cohorts of patients who underwent muscle or fasciocutaneous flaps. RESULTS: Three hundred fifty-nine flap procedures were performed. Of these procedures, 197 were muscle (55 percent) and 152 were fasciocutaneous flaps (42 percent). There was no difference in overall flap complications between groups (30 percent versus 26 percent; p = 0.475). However, there was a significantly higher flap failure rate in the muscle compared with the fasciocutaneous group (13 percent versus 6 percent; p = 0.030). Although there were more overall extremity complications in the muscle group (59 percent versus 47 percent; p = 0.030), there were no significant differences in soft-tissue infection, osteomyelitis, or amputation rates. CONCLUSIONS: There are many flap options that provide adequate coverage in extremity salvage. Complication rates did not differ significantly between muscle and fasciocutaneous flaps, with one exception--flap failure rates were significantly higher in our muscle-based flap cohort of patients. Nonetheless, each of these flap types has utility in our patients based on individual wounding patterns, flap availability for reconstruction, and rehabilitation goals. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Flap coverage outcomes following vascular injury and repair: chronicling a decade of severe war-related extremity trauma.

BACKGROUND: Combat-related extremity injuries frequently require vascular repair within the combat theater before undergoing definitive reconstruction. This study examines the outcomes of early vascular repair with secondary soft-tissue extremity reconstruction over the past decade of war trauma. METHODS: War-related extremity injuries necessitating a downrange vascular procedure followed by a definitive limb reconstruction were reviewed. Patient demographics, type and location of vascular injuries, vascular intervention, and soft-tissue reconstruction procedures were examined. Outcomes of vascular repair, tissue transfer, and limb salvage were analyzed. RESULTS: From 2003 to 2012, 79 extremities in 78 patients had a vascular injury requiring in-theater intervention followed by 87 staged flap reconstructions performed distal to the vascular repair. Of the 74 arterial injuries requiring intervention, 27 were proximally located, with 73 percent requiring bypass. The early primary patency rate was 66 percent and the early primary-assisted patency rate was 93 percent for proximal artery repair procedures. The flap complication rate was 31 percent. Overall complications were examined by subtype and were not significantly different compared with flaps performed without a proximal vascular injury in the same limb. The flap success rate (93 percent) and the limb salvage rate (81 percent) were similar to the comparison cohort. CONCLUSIONS: This represents one of the largest series of traumatic extremity injuries requiring secondary limb reconstruction with tissue transfer following a vascular intervention. The authors identified no significant difference in outcomes related to flap coverage or limb salvage for patients with or without vascular injuries. Reconstructive options in combat extremity trauma are not limited by proximal vascular injury. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Delivery of electroconvulsive therapy in Canada: a first national survey report on devices and technique.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment for mood and other psychiatric disorders. Despite widespread use, the specifics of ECT practice in Canada are largely unknown. A nationwide survey designed to document current delivery was therefore conducted. METHOD: One hundred seventy-five Canadian ECT delivery sites were identified. A detailed questionnaire (13 pages, 76 questions grouped in 11 subheadings) was developed, translated into French, piloted, and then forwarded to all ECT centers. RESULTS: Return rate for the full questionnaire was 61%. Wide-ranging information pertaining to ECT was gathered. This article, which addresses the data specifically pertaining to ECT devices, electrical stimulus parameters and electrode placements, showed that many core aspects of ECT practice in Canada are in keeping with current recommendations. The use of old sine wave devices is virtually nonexistent. Electroencephalographic (EEG) monitoring of seizures is widespread. CONCLUSIONS: Specific concerns were identified, including the need for access to back-up devices at all centers, the lack of ECT credentialing requirements by Canadian hospitals, and a striking variation in dosing practices. An audit of Canadian practice and the development of a National Standards Document would be an essential next undertaking.

Electroconvulsive therapy teaching in Canada: cause for concern.

AIM: The objective of this study was to present survey data on the teaching of electroconvulsive therapy (ECT) in health care centers across Canada. METHODS: Of 1273 centers identified, 175 were found to practice ECT. These centers were asked to complete a questionnaire, and 107 (61%) of them answered 5 questions dealing specifically with ECT teaching. These questions were as follows: (1) Does your facility have an ECT teaching program for residents in psychiatry? (2) How is ECT taught to residents in psychiatry? (3) If direct supervision of the administration of ECT is a requirement of the psychiatry training program, is there a minimum number of supervised treatments or minimum duration of training period? (4) Do residents provide unsupervised ECT at your center? (5) Which other groups of learners, if any, are provided with orientation, teaching, or training in ECT? RESULTS: Sixty percent of respondents had no ECT teaching program for psychiatry residents. Pedagogical methods varied, ranging from direct observation of ECT treatments to directed readings. Few centers required a minimum number of supervised treatments. No resident-administered ECT is performed without direct supervision. Interestingly, various groups of health care professionals were often invited to participate in ECT training. CONCLUSIONS: The situation regarding ECT teaching continues to be a cause for concern given the noted absence of organized, structured, and mandatory programs. No resident administering ECT, however, goes unsupervised, which is in keeping with good practice. Electroconvulsive therapy is taught in many different ways, and teaching is accessible to different groups of health care professionals. However, much remains to be done to standardize ECT teaching to render this therapy available to all those who need it and to overcome the stigma and bias associated with it.

Canadian survey of perianesthetic care for patients receiving electroconvulsive therapy.

OBJECTIVES: We report on the anesthesia subsection of a comprehensive nationwide survey (Canadian Electroconvulsive Therapy Survey/Enquête canadienne sur les electrochocs) on the practice of electroconvulsive therapy (ECT) in Canada. METHODS: This comprehensive survey was sent to the 175 Canadian institutions identified as providers of ECT in 2007. Among other topics, 9 anesthesia-related questions were administered regarding anesthesiology consultation; high-risk patients; credentials of the anesthesia provider; monitoring, airway, and resuscitation equipment; anesthetic induction, muscle relaxant, vasoactive, and other perianesthetic drugs and practices; and postanesthetic discharge. RESULTS: Sixty-one percent (107/175) of the institutions returned completed survey questionnaires. More than 70% of the sites reported pre-ECT anesthesiology consultation for all (61%) or most (11%) patients. In more than 90%, a Canadian Royal College-certified anesthesiologist, or equivalent, provided anesthetic care. Routine use of oximetry, electrocardiography, and blood pressure monitoring were reported by all but 2 sites; use of bite block was reported by all but 4 sites; and preoxygenation was reported by all but 7 sites. Dantrolene and capnography were not reported as readily available by 35% and 40%, respectively, with comparatively less frequent availability at non-operating room and lower-volume sites. CONCLUSIONS: These results suggest safe practices of anesthesia for ECT in Canada. Further attention needs to be paid to ready availability of dantrolene and capnography, particularly at non-operating room ECT sites. Improvements in anesthetic care of patients undergoing ECT may be realized through continued knowledge translation efforts and by expanding access to currently unavailable anesthetic induction agents and, in some settings, limited clinical anesthesiology resources.

The Canadian Survey of Standards of Electroconvulsive Therapy Practice: a call for accreditation.

OBJECTIVE: To report the results of the policies and procedures subsection of a nationwide electroconvulsive therapy (ECT) survey: Canadian Electroconvulsive Therapy Survey/Enquête canadienne sur les electrochocs. METHOD: We contacted 1273 registered health care institutions in Canada and invited the 175 centres identified as providing ECT to complete a comprehensive postal questionnaire. Nonresponding sites were repeatedly reminded and then eventually contacted by telephone. RESULTS: Sixty-one per cent (107/175) of the institutions returned survey questionnaires. Most (84%) of the responding sites have a written general policy for the delivery of ECT. Only 27% of respondents indicated having some written policy for managing concurrent medications during ECT, and practice was quite variable regarding individual psychotropics. Informed consent was usually obtained by the attending physician (88%), and most sites indicated conveying information before ECT by using interdisciplinary and multimodal means. Almost all of the sites (93%) discharged outpatients with accompaniment home by a responsible adult. CONCLUSIONS: It is reassuring to note that general ECT policies and procedures do exist in most Canadian ECT centres. Wider variations in practice were observed in several areas, such as the elements of consent provided to patients and families, the use of concurrent medications, and the degree of supervision on discharge home after outpatient ECT. However, adherence to these policies was not captured by the results of the survey. Based on experiences in other countries, establishing a Canadian ECT accreditation service could further improve standards of practice.

Access to electroconvulsive therapy services in Canada.

OBJECTIVES: We sought to determine factors governing access to electroconvulsive therapy (ECT) in Canada. METHODS: We contacted all 1273 registered health care institutions in Canada and invited the 175 centers identified as providing ECT to complete a comprehensive questionnaire. To determine geographic access to ECT, we used a geographic information system, population density data, and road network data. Responses to 5 questions from the questionnaire were used to identify local barriers to access. RESULTS: Approximately 84% of the population in the 10 Canadian provinces live within a 1-hour drive of an ECT center, but 5% live more than 5 hours' drive away. There was significant province-to-province variation, with all of the citizens of Prince Edward Island living within 2 hours of an ECT center but 12.5% of those in Newfoundland and Labrador living more than 5 hours' distance away. There are no ECT services at all in the 3 territories, which contain 3% of the Canadian population. Nongeographic barriers to access included inadequate human resources, particularly, a lack of anesthesiologists, in 59% of the centers; logistical impedances (52%); space limitations (45%); strictures on the hiring of adequate staff (29%); imposed limits to number of treatments or to operating or postanesthetic room time (28%); and a lack of funds to purchase up-to-date ECT or related anesthesiology equipment (14%). CONCLUSIONS: Electroconvulsive therapy is geographically accessible for most Canadians. Even when geography is not a factor, however, there are significant barriers to access resulting from inadequate availability of qualified professional staff, treatment areas, and funding.

High-resolution secondary ion mass spectrometry reveals the contrasting subcellular distribution of arsenic and silicon in rice roots.

Rice (Oryza sativa) takes up arsenite mainly through the silicic acid transport pathway. Understanding the uptake and sequestration of arsenic (As) into the rice plant is important for developing strategies to reduce As concentration in rice grain. In this study, the cellular and subcellular distributions of As and silicon (Si) in rice roots were investigated using high-pressure freezing, high-resolution secondary ion mass spectrometry, and transmission electron microscopy. Rice plants, both the lsi2 mutant lacking the Si/arsenite efflux transporter Lsi2 and its wild-type cultivar, with or without an iron plaque, were treated with arsenate or arsenite. The formation of iron plaque on the root surface resulted in strong accumulation of As and phosphorous on the epidermis. The lsi2 mutant showed stronger As accumulation in the endodermal vacuoles, where the Lsi2 transporter is located in the plasma membranes, than the wild-type line. As also accumulated in the vacuoles of some xylem parenchyma cells and in some pericycle cells, particularly in the wild-type mature root zone. Vacuolar accumulation of As is associated with sulfur, suggesting that As may be stored as arsenite-phytochelatin complexes. Si was localized in the cell walls of the endodermal cells with little apparent effect of the Lsi2 mutation on its distribution. This study reveals the vacuolar sequestration of As in rice roots and contrasting patterns of As and Si subcellular localization, despite both being transported across the plasma membranes by the same transporters.

Soft tissue management of war wounds to the foot and ankle.

This article details the experiences of United States military reconstructive surgeons in the soft tissue management of war wounds of the foot and ankle resulting from the conflicts in Iraq and Afghanistan. War wounds from this conflict are commonly caused by blast and fragmentation, and are characteristically extensive, heterogeneous, and severe. Multiple serial débridement episodes are routinely necessary because of deterioration of the wounds over time, which is in contrast to civilian trauma wherein fewer débridement episodes are generally required. Wound therapy adjuncts, such as subatmospheric wound dressing and synthetic dermal replacement, have been used extensively with favorable results. Pedicled flaps, such as the distally based sural neurofasciocutaneous flap, are reliable, and avoid the risks and technical demands associated with microsurgery. Free tissue transfer, such as the anterolateral thigh flap, the latissimus dorsi muscle flap, and the rectus abdominis muscle flap, are powerful reconstructive tools, and have been extensively used in the reconstruction of war wounds of the foot and ankle.

Trafficking of storage proteins in developing grain of wheat.

The processing properties of the wheat flour are largely determined by the structures and interactions of the grain storage proteins (also called gluten proteins) which form a continuous visco-elastic network in dough. Wheat gluten proteins are classically divided into two groups, the monomeric gliadins and the polymeric glutenins, with the latter being further classified into low molecular weight (LMW) and high molecular weight (HMW) subunits. The synthesis, folding and deposition of the gluten proteins take place within the endomembrane system of the plant cell. However, determination of the precise routes of trafficking and deposition of individual gluten proteins in developing wheat grain has been limited in the past by the difficulty of developing monospecific antibodies. To overcome this limitation, a single gluten protein (a LMW subunit) was expressed in transgenic wheat with a C-terminal epitope tag, allowing the protein to be located in the cells of the developing grain using highly specific antibodies. This approach was also combined with the use of wider specificity antibodies to compare the trafficking and deposition of different gluten protein groups within the same endosperm cells. These studies are in agreement with previous suggestions that two trafficking pathways occur in wheat, with the proteins either being transported via the Golgi apparatus into the vacuole or accumulating directly within the lumen of the ER. They also suggest that the same individual protein could be trafficked by either pathway, possibly depending on the stage of development, and that segregation of gluten proteins both between and within protein bodies may occur.