Mircette

Larry L. Cunningham, Jr., DDS, MD, FACS

• Associate Professor, Residency Director, and
• Chief, Division of Oral and Maxillofacial Surgery
• University of Kentucky College of Dentistry
• Lexington, Kentucky

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Epithelioid was 39 (67%), biphasic was 14, sarcomatoid was 2, and special variants was 3. Atrial fbrillation was the most common morbidity, and developed in 20 patients (34%). Background: Although surgical intervention improves survival for Postoperative median follow-up period was 6 years and 7 months. This study were 32%, 63%, and 37 months, and those of recent 29 epithelioid sought to examine treatment patterns and survival between black patients from 2011 were 43%, 72%, and 59 months (Figure). Multivariable logistic regressions were used to evaluate the racial diferences in the extent of surgery, receipt of additional treatment (chemotherapy and/or radiotherapy), and 30/90day mortality, while accounting for clinical and demographic factors. A multivariable Cox proportional hazards model was used to assess the independent associations of race with overall survival. Association between race and survival was also analyzed using a 1:1 propensity score matching with the greedy algorithm. There was also a statistically rising due to a long lag time in malignant transformation. As such, analysis supports the concept that mesothelin and fbulin-3 in control development of novel therapeutic options is urgently needed. Mice with 1Fukushima Medical University Department of Chest Surgery, Fukushima/ tumor size >600mm3 were considered reaching humane endpoint. In terms of histology type, Claudin15 was 50% and Calretinin was 65% in the epithelial type, while Claudin15 was 80% and Calretinin was 40% in the biphasic type. Taioli adenocarcinomas showed no or very low-level expression of Icahn School of Medicine at Mount Sinai, New York/United States of America Claudin15. The following meta-analysis examines average levels of these biomarkers in blood Keywords: tight junctions, malignant pleural mesothelioma, Claudin and pleura in comparison to several control groups. Preclinical studies di Torino and University of Torino, Torino/Italy show that efcacy increases with the intensity of the electric feld. The Registry of Malignant Mesothelioma feld intensities within the lungs of the models were evaluated. Sensitivity and specifcity of the initial to electromagnetic absorption, was calculated. Result: intensities throughout the lungs exceeded the therapeutic threshold of 1 V/cm in all models. Yumuk1 1 1 1 1 1Marmara University School of Medicine, Marmara University Pendik Training Data of 552 patients were analyzed. Sensitivity Research Hospital, Istanbul/Turkey and specifcity were 93% and 100%, respectively. Of those, 10 (71%) had an initial Background: Prognostic signifcance of Laboratory Prognostic diagnosis of chronic pleuritis, 3 (28. Fica1 1 Forces patients, their family and friends and anyone interested in fnding out more. The prognosis is at the Armed Forces community focusing on raising awareness of dismal because of early spreading and scarcity of therapies. Awareness events proved to (extrapleural pneumonectomy or pleurectomy/decortication) has be a major factor in the growth of the project providing excellent shown some improvement in patient survival, even more important networking opportunities and resulting in invitations to speak and with the addition of radio or chemotherapy. A list of organisations and relevant groups advanced disease are treated with palliative chemotherapy or was developed in preparation for the national roll out. The development of this service has been very well received by surgery or costly and patient-consuming radio or chemotherapy. Centre A is a public Hospital with Keywords: Mesothelioma, Service Development, Armed forces/ an assigned population of 1 million, without thoracic surgeon and veterans oncologic committee, and patients were seldom referred to palliative chemotherapy. Centre B is a terciary, referral academic university Hospital with Thoracic surgeons and oncologic committee. Centre A had 30% of patients with presence of metastasis at the time of diagnosis, while centre B had A. The 2 centres had radically diferent mostly afects men over 65 years of age; It is linked to exposure resources and approaches to treat this illness, however, even though to asbestos, normally 15-40 years prior to diagnosis. Its industrial there is a tendency towards better survival in Centre B, there were nature diagnosis can mean navigating complex health, legal and no statistically diferences between both groups. Clinical experience and anecdotal evidence from appear increasing the follow-up time or including more centres, health professionals indicate that this veterans encounter particular alternatively, the rarity of this disease could produce oncologic challenges in recognising and reporting early symptoms, getting a teams with not enough experience dealing with it afecting survival diagnosis and accessing care and support, including fnancial help. Semi-structured interviews of up to 15 veterans with mesothelioma and 15 family A. Valued sources of a grant from this scheme to support a three year project to develop support included specialist mesothelioma medical and nursing staf a specialist service for Armed Forces personnel and veterans as well as mesothelioma/asbestos charities. Kaplan-Meier curves were performed to estimate time to intracranial progression, survival from diagnosis of brain metastases, and overall survival. Median survival from diagnosis of brain metastases was survival estimates at 12 and 24 months were 30. Potential reasons for this result For patients with synchronous brain metastases at presentation (104 include a lack of tools to select patients for radical treatment. For all patients without brain metastases at presentation, extracranial disease in this patient group. However, even after completing this intensive 1 1 2 1 1 1 treatment, postoperative recurrence will develop in a subset of F. Harris, 4 1 1 1 1 considered to have systemic disease, which is regarded as incurable. Woolf1 1 1 Nevertheless, some patients have a relatively good prognosis following this treatment, even after postoperative recurrence. This analysis focused on 71 tumor and initial recurrence, was 11 months (range, 4. Of the 62 of these patients able to be assessed retrospectively, the Electronic patient records were accessed in March 2019 to determine brain was the most frequent location of recurrence (31%), followed initial extracranial disease treatment and date of death or last follow by the lung (27%), lymph nodes (24%), and bone (15%). Result: 30 patients received radical treatment (18 radiotherapy had oligometastatic recurrence and 30 underwent local treatment alone, 11 chemo-radiotherapy and one surgery) and 24 received with curative intent. Local treatment was most frequently given to palliative treatment (17 chemotherapy, four radiotherapy and three patients with oligometastatic recurrence (P < 0. These patients can beneft from defnitive treatment to primary tumour and loco-ablation of metastases. From August 2014 to April 2019, with a median follow up of 13 months, forty-seven patients were enrolled. Grade 1, 2 and 3 pneumonitis were Background: Pleural dissemination or malignant pleural efusion observed in the 69. However, recent studies suggested that complete removal of the disseminated nodule in combination with lung resection is associated with long-term survival when dissemination is limited. All but one patient were followed until December 2018 or death, and the follow-up period for surviving patients ranged from 48 to 361 months (median 158 months). Furthermore, 3 out of the 4 patients were still alive at 361 months, 300 months, and 211 months, respectively. Keywords: Non-Small Cell Lung Cancer, pleural dissemination, extrapleural pneumonectomy P2. Multivariate Cox regression analysis was performed to establish the predictive model. A prospective internal validation cohort contained 14 patients from January 2018 to December 2018. The incidence of minimally invasive cases may allow the development of efective mutations was calculated and compared among diferent subtypes. Biological characterizazion of these kind of patients will likely improve the understanding of their unusual course. Gronberg1,2 1The First Afliated Hospital of Guangzhou Medical University, National 1St. Microsatellite were stable except for 3 cases with low instability and 3 not evaluable cases. Next Generation Sequencing was performed with IonTorrent (ThermoFisher Scientifc, Life Technologies) by using P2. Main clinical and biological characteristics of the two populations are Background: Incidence of lung cancer is rising in India, which detailed in the table. During grossing, two tumor blocks were made, one for immunohistochemistry studies and other for mutation testing. In Smoking status highcellularity, lowtumor fraction cases, tumor enrichment was Former/current 76. The mutation rate in comprehensive evaluation of the composition and distribution of lung adenocarcinoma is approximately 50% in Japan. Correlation was tested by chi-square test and no signifcant diference when immune infltrates were compared by p value of less than 0. Our results showed that the infltration levels of most T-cell cancer but also cervical cancer of uterus and gastrointestinal stromal subpopulations within tumor did not signifcantly associated with tumor, and developed angiosarcoma of the skin. Result: Collectively, we identifed breast cancer group and no malignancy group (p=0. One patient in Japan, suggesting underlying common oncogenic molecular had no mutation detected from this panel. Only sequencing of 425 cancer genes related to treatment, genetic risks 7% of adenocarcinomas (9/134) and 4% of squamous cell carcinomas and tumorigenesis. Lin,1 1 1 1 1 4 4 4 centrally located, with no morphological squamous and glandular J. The addition of molecular testing is useful to defne discrepancies in challenging cases Keyword: pathology molecular multiple P2. In certain cases, the distinction based only on histological to 24%, 25% to 49%, fi50% (p=0. Method: An observational study was Dako 22C3 were inconsistent among three observers in all categories performed including 22 lung cancer cases with more than one nodule above, with all p values greater than 0. Only 2 nodules per patient were studied, selected according to histological or sizing criteria. Tumors were classifed according to both histological criteria into 3 categories: Synchronous, metastatic or undefned. Cases sharing at least 1 somatic mutation or fusion were considered metastatic tumors. Cases with diferent somatic mutations/fusions were considered synchronous tumors and those showing no mutations/fusions were classifed as undetermined. Result: Tumor nodule size in surgical specimens varied between 0,3 and 4 cm, whereas the biopsy case corresponded to an 8-cm mucinous adenocarcinoma. Based on molecular testing, we found 6 (27,27%) related and 14 (63,64%) non-related tumors, whereas only 2 cases (9,09%) remained undetermined. Surgical and pathology reports were reviewed by an independent expert committee for tumor staging. These data will be subsequently updated on a larger number of patient and correlated to clinical follow-up. This is partly due to the use of diferent antibodies, staining platforms and positivity cut-ofs. Infltration pattern has been clustered in 4 diferent categories: brisk-difuse, non-brisk P2. Currently, the lymphocyte infltration pattern appeared to have a negative impact thresholds of fi1% and fi50% of tumor cells stained are clinically (p=0. Slides were digitalized and scored for the percentage of tumor cells with membranous staining by 161 pathologists using an online digital platform. The median 1Institute of Pathology, University of Bern, Bern/Switzerland, 2Department age was 69 (range 31-81) years and the majority of patients were of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, men (85%). Histologically, 52 cases were squamous cell carcinomas, Bern/Switzerland, 3Pathologie Langgasse, Ittigen/Switzerland, 4Division of 19 adenocarcinomas, 9 pleomorphic carcinoma and 4 other types. Conclusion: Our data showed that a regimens is currently evaluated in clinical trials. Matsuo Kitasato University School of Medicine, Sagamihara/Japan Background: Understanding of the immune contexture of tumor microenvironments might provide knowledge predicting the efect of immunotherapies and prognosis. Method: the pathology archive at Wythenshawe Hospital was searched for cases with adequate material over a period spanning 2010-2016. To test hypotheses, we used the chi-square test, and the predictive factor search was performed through logistic regression. Conclusion: the molecular profle of lung carcinoma was similiar to what is described in the literature. It would be interesting to understand the biological behavior of this group of tumors and, in the future, to study the role of eventual therapeutic associations. In addition to heterogeneity of expression, sampling of recurrent rather than residual disease may contribute to discrepancies.

The patient may complain of a burning sensation and frequently be alarmed by the enlarged papillae birth control pills every 3 months purchase 15mcg mircette fast delivery, fearing a cancer birth control pills 1950s order 15 mcg mircette. Diseases of the Tongue Hypertrophy of the Fungiform Papillae Sublingual Varices the fungiform papillae appear as multiple small In persons more than 60 years of age varicosities round red nodules along the anterior portion of of the sublingual veins are common birth control pills with iron order genuine mircette on line. Sublingual varices are benign and they are usually Excessive smoking birth control zero copay discount mircette 15mcg with visa, alcohol consumption birth control pills 8667 buy mircette 15mcg, hot discovered accidentally by the patient birth control pills joint pain trusted mircette 15mcg. Diseases of the Lips Median Lip Fissure Characteristically, the lesions do not extend beyond the mucocutaneous border. A burning senMedian lip fissure is a relatively rare disorder that sation and feeling of dryness may occur. Unmay appear in both lower and upper lips and is treated, angular cheilitis may last for a long time, more common in males than females. Recently, a hereditary predisposiActinic cheilitis may occur as an acute or chronic tion has been proposed. Chronic actinic cheilitis is observed in sents as a deep inflammatory, persistent vertical older persons as a result of long-standing exposure fissure at the middle of the lip, usually infected by to sunlight (such as farmers, seamen) and characbacteria and Candida albicans (Fig. In persissively, the epithelium becomes thin, atrophic with tent severe cases, surgical excision with plastic small whitish-gray areas intermingled with red reconstruction is recommended. There is an increased risk of development of Angular Cheilitis leukoplakia and squamous cell carcinoma. Angular cheilitis, or perleche, is a disorder of the the differential diagnosis should include lupus lips caused by several factors, such as riboflavin erythematosus, lichen planus, contact cheilitis, deficiency, iron deficiency anemia, Plummer-Vinleukoplakia, and squamous cell carcinoma. Histopathologic examination is many cases are due to loss of proper vertical essential to exclude cancer. In such cases, a fold is formed at the angles fluorouracil, and, in severe cases, surgical excision of the mouth in which saliva continuously moisof the involved areas of the lip. It has been shown that microorganisms, such as Candida albicans, Streptococci, Staphylococci, and others may superimpose or cause angular cheilitis. Clinically, the condition is characterized by maceration, fissuring, erythema with erosions, and crusting at the commissures (Fig. Diseases of the Lips Exfoliative Cheilitis Cheilitis Glandularis Exfoliative cheilitis is a chronic inflammatory disCheilitis glandularis is an uncommon chronic order of the vermilion border of the lips, which is inflammatory disorder involving chiefly the lower characterized by the persistent formation of scales lip. Emotional stress women with emotional stress and may coexist with and chronic exposure to sunlight have also been atopy. Clinically, it consists of enlargement may become aggravated by cold or very hot of the lip due to minor salivary gland hyperplasia weather. Clinically, exfoliative cheilitis consists of and chronic inflammatory infiltration (Fig. This pattern is repetitive, resulting in thickopenings from which mucus or mucopustular fluid ening, scaling, and crusting of one or both lips may be expressed on pressure. The last two forms are a result of the differential diagnosis includes contact cheilitis microbial infection and the clinical signs and and actinic cheilitis. Topical moistening agents (such as the differential diagnosis includes cheilitis cocoa butter) and topical steroids may be helpful. Histopathologic examination is Contact Cheilitis essential in establishing the diagnosis. The most common causes that have been incriminated are lipsticks, lip salves, dentrifices, mouthwashes, foods, etc. Clinically, contact cheilitis is characterized by mild edema and erythema, followed by irritation and scaling (Fig. The differential diagnosis includes exfoliative cheilitis, and plasma cell cheilitis. Treatment consists of discontinuing all contact with the offending substance and use of topical steroids. Clinically, it is characterized by diffuse redbelieved to be a monosymptomatic form of the ness with slight swelling of the vermilion border of Melkersson-Rosenthal syndrome. Similar lesions have been cheilitis granulomatosa is characterized by paindescribed on the gingiva and the tongue. This less, diffuse swelling, frequently of the lower lip group of lesions is identical to plasma cell balanitis and rarely the upper lip or both (Fig. Small vesicles, erosions, and cheilitis, allergic reactions, actinic cheilitis, eryscaling may occasionally appear. The disease usuthroplakia, candidosis, lichen planus, and lupus ally has a sudden onset and a chronic course, with erythematosus. Topical steroid ointments, intralesional injection of triamcinolone, or systemic steroids may be useful in some cases. Soft-Tissue Cysts Mucocele Ranula Mucoceles, or mucous cysts, originate from minor Ranula is a variety of mucocele localized exclusalivary glands or their ducts and are the most sively in the floor of the mouth. Two types ducts of the submandibular gland, sublingual are recognized: extravasation mucoceles are most gland, or the accessory salivary glands of the floor common (more than 80%) and their pathogenesis of the mouth, and its pathogenesis is similar to is related to duct rupture from trauma due to that of mucoceles. Clinically, it presents as a biting; retention mucoceles are rare and their smooth, fluctuant, painless mass in the floor of the pathogenesis is related to partial obstruction of mouth, just lateral to the lingual frenum (Fig. Extravasation-type mucoceles display a peak the average size is 1 to 2 cm, but larger lesions incidence during the second and third decades, may form, causing speech and swallowing probwhereas the retention-type mucoceles are more lems. However, there is the differential diagnosis includes dermoid cyst, no sex predilection, and they may occur at all lymphoepithelial cyst, abscess of the floor of the ages. Histopathologic examination bicuspids, less commonly on the buccal mucosa, floor of the mouth, palate, tongue, and very selestablishes the diagnosis. Clinically, mucoceles are painless, spherical, solitary fluctuant masses that vary in size from a few millimeters to several centimeters in diameter (Figs. Superficial cysts are translucent and bluish, whereas deeper lesions have the color of normal mucosa. Usually, they appear suddenly, rapidly reaching their final size, and may persist for several weeks to several months. Sometimes they empty partially and then reform due to accumulation of fresh fluid. Soft-Tissue Cysts Lymphoepithelial Cyst Dermoid Cyst Lymphoepithelial cyst of the oral mucosa is an Dermoid cyst is an uncommon developmental uncommon developmental lesion that is probably lesion arising from embryonic epithelial remnants. It usually becomes apparent frequently appears in early adulthood and both between the ages of 20 and 50 years and is slightly sexes are equally affected. The intraoral cyst occurs most normal or slightly reddish color and characteristic frequently in the floor of the mouth and the soft doughlike consistency on palpation (Fig. Clinimuscle, it displaces the tongue upward, producing cally, it is a mobile, painless, well-defined, firm, difficulties in mastication, speech, and swallowand elevated nodule with a yellowish or reddish ing. The differential diagnosis includes lymphoepithethe differential diagnosis includes lymph node, lial cyst, ranula, cystic hygroma, and abscess of dermoid cyst, mucocele, lipoma, and other benign the floor of the mouth. Soft-Tissue Cysts Eruption Cyst Gingival Cyst of the Adult Eruption cyst is a variety of dentigerous cyst that Gingival cyst is rare in adult patients and may be is associated with an erupting deciduous or permalocated either in the free or attached gingiva. It is commonly located at the site of originates from epithelial rests (such as dental eruption of the canines and molars. It is more frequent in eruption cyst appears as well-demarcated, flucpatients more than 40 years of age and is located tuant, and soft swelling directly overlying the most often to the mandibular vestibule between alveolus at the site of the erupting tooth. Clinically, it often, the color is blue, or dark red when the cyst appears as a small well-circumscribed nodule of cavity is filled with blood (Fig. The clinical the gingiva, covered with normal mucosa with a features are characteristic and the diagnosis is size varying from few millimeters to 1 cm in obvious. The differential diagnosis includes hemangioma, the differential diagnosis includes mucocele, hematoma, amalgam tattoo, oral pigmented nevi, periodontal abscess, peripheral ossifying fibroma, and malignant melanoma. Clinically, it appears as multiple or solitary asymptomatic whitish nodules 1 to 3 mm in diameter in the alveolar mucosa (Fig. The differential diagnosis includes lymphangioma and congenital epulis of the newborn. Palatine Papilla Cyst the differential diagnosis includes tooth abscess, soft tissue abscess, radicular cyst, mucocele, Palatine papilla cyst is a variety of the minor salivary gland neoplasms, and mesenchynasopalatine cyst that arises from epithelial rests mal neoplasms. Histopathologic examination is soft swelling of the palatine papilla, covered with necessary to establish the diagnosis. The differential diagnosis includes dental and Thyroglossal Duct Cyst periodontal abscess, trauma of the palatine Thyroglossal duct cyst is a rare developmental papilla, fibroma, and other benign tumors of the lesion that may form anywhere along the thyrooral connective tissue. When it is localized in the oral cavity, it is usually found on the dorsum of the tongue close to the foramen Nasolabial Cyst caecum (Fig. It grows slowly Nasolabial cyst is a rare soft-tissue cyst with and, if significantly enlarged, may cause dysunclear pathogenesis. A fistula may form on occasion, opening gested that the cyst develops from the inferior and on the skin or mucosal surface (Fig. It is more frequent in females usually between 40 50 years the differential diagnosis includes benign and of age. Clinically, nasolabial cyst appears as a soft malignant tumors and median rhomboid glossitis. Radioisotope and scintiscanning illa, exactly opposite to the cuspid, or in the floor are useful. Viral Infections Primary Herpetic Gingivostomatitis bridization) confirm the diagnosis in difficult cases. An elevated serum titer of antibodies is also Primary herpetic gingivostomatitis is the most fresuggestive of the disease. The cally is indicated, but in most cases treatment is cause of the disease is the herpes simplex virus, symptomatic. Recurrent herpes infection differs from prithe oral mucosa is red and edematous, with mary infection in that the vesicles are closely numerous coalescing vesicles. Within 24 hours, grouped, smaller in size, and the constitutional the vesicles rupture, leaving painful small, round, symptoms are absent. Predisposing factors that shallow ulcers covered by a yellowish-gray may precipitate reactivation of the virus include pseudomembrane and surrounded by an emotional stress, febrile illness, needle trauma erythematous halo (Fig. The In addition, recently it has been recorded that ulcers gradually heal in 10 to 14 days without recurrent herpetic lesions is a relatively common scarring. The clinical features consist of a small number Lesions are almost always present on the gingiva, of discrete vesicles arranged in clusters, usually resulting in acute gingivitis, which may be free of localized on the hard palate and the attached vesicles (Fig. The vesicles rupture in a few hours, leavmucosa may also be affected, that is, the buccal ing small, 1 to 3 mm ulcers that heal spontaneously mucosa, tongue, lips, and palate. The differential diagnosis includes herpetiform the differential diagnosis includes herpetiform ulcers, aphthous ulcers, hand-foot-and-mouth disulcers, aphthous ulcers, herpes zoster, streptococease, herpangina, streptococcal stomatitis, acute cal stomatitis, gonococcal stomatitis, primary and necrotizing ulcerative gingivitis, erythema mulsecondary syphilis. Histopathologic studies, monoclonal antibodies, isolation, and culture of the virus (nucleic acid hy15. Primary herpetic gingivostomatitis, erythema and multiple ulcers on the gingiva. Oral from its location in nerve ganglia, and it is by far mucosal lesions are almost identical to the the most common form of recurrent herpetic cutaneous lesions. It affects women more often than men which may simulate pulpitis, precede oral lesions. Prodromal sympwhich in 2 to 3 days rupture, leaving ulcers surtoms, such as burning, mild pain, and itching, rounded by a broad erythematous zone (Figs. The ulcers heal without scarring in 2 to 3 cally, it is characterized by edema and redness on weeks. Postherpetic trigeminal neuralgia is the the vermilion border and the adjacent perioral most common complication of oral herpes zoster. Rarely, osteomyelitis, necrosis of the jaw bone, or the vesicles soon rupture, leaving small ulcers loss of teeth may occur in immunocompromised that are covered by crusts and heal spontaneously patients. The diagnosis of oral herpes zoster is based on Frequently, recurrences may be associated with clinical criteria. Cytologic examination confirms the differential diagnosis includes traumatic lesions, primary and secondary syphilis, and imvirally modified epithelial cells. Low-dose Treatment is symptomatic and is strengthened by corticosteroids (such as 15 to 20 mg prednisolone topical application of acyclovir. Acyclovir and other antiviral agents may be helpful in severe Herpes zoster is an acute localized viral disease cases. Herpes zoster affects elderly persons, usually more than 50 years old, and is rare in infants and children. The thoracic, cervical, trigeminal, and lumbosacral dermatomes are most frequently affected. Clinically, the first manifestation of the disease is usually tenderness and pain in the involved dermatome. After 2 to 4 days, the eruptive phase follows, characterized by grouped maculopapules on an erythematous base, which rapidly form vesicles and in 2 to 3 days evolve into pustules. The unilateral location of the lesions is the most characteristic clinical feature of herpes zoster. Viral Infections Varicella streptococcal and gonococcal pharyngitis, and erythema multiforme. Varicella (chickenpox) is an acute exanthematous Laboratory tests to confirm the diagnosis are the and highly contagious disease of childhood caused isolation of the virus and serology, although they by primary infection with the varicella-zoster are not usually needed. New elements appear in successive waves over 2 to 4 days and the presence of Acute lymphonodular pharyngitis is an acute felesions at different stages is a characteristic clinical brile disease caused by Coxsackie virus A10. The trunk, face, and scalp are most comthe disease frequently affects children and monly involved. Oral lesions are days by a characteristic nonvesicular eruption on common and show a predilection for the palate the uvula, soft palate, anterior tonsillar pillars, and the lips. The size of the lesions varies from 3 to 6 mm the differential diagnosis of oral lesions includes in diameter and they last 4 to 8 days. Laboratory tests to confirm the diagnosis are the isolation of the virus and serologic examination.

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Governments at the appropriate level, and with the support of the relevant international and regional organizations, should collect, analyse, and disseminate information on human resources, the role of Governments, local communities and non-governmental organizations in social innovation and strategies for rural development. Help develop information available through non-governmental organizations and promote an international ecological agricultural network to accelerate the development and implementation of ecological agriculture practices. The Conference secretariat has estimated the average total annual cost (1993-2000) of implementing the activities of this programme to be about $4. Launch applied research on participatory methodologies, management strategies and local organizations. Improving farm production and farming systems through diversification of farm and non-farm employment and infrastructure development Basis for action 14. Agriculture needs to be intensified to meet future demands for commodities and to avoid further expansion onto marginal lands and encroachment on fragile ecosystems. Increased use of external inputs and development of specialized production and farming systems tend to increase vulnerability to environmental stresses and market fluctuations. There is, therefore, a need to intensify agriculture by diversifying the production systems for maximum efficiency in the utilization of local resources, while minimizing environmental and economic risks. Where intensification of farming systems is not possible, other on-farm and off-farm employment opportunities should be identified and developed, such as cottage industries, wildlife utilization, aquaculture and fisheries, non-farm activities, such as light village-based manufacturing, farm commodity processing, agribusiness, recreation and tourism, etc. To improve farm productivity in a sustainable manner, as well as to increase diversification, efficiency, food security and rural incomes, while ensuring that risks to the ecosystem are minimized; b. To enhance the self-reliance of farmers in developing and improving rural infrastructure, and to facilitate the transfer of environmentally sound technologies for integrated production and farming systems, including indigenous technologies and the sustainable use of biological and ecological processes, including agroforestry, sustainable wildlife conservation and management, aquaculture, inland fisheries and animal husbandry; c. To create farm and non-farm employment opportunities, particularly among the poor and those living in marginal areas, taking into account the alternative livelihood proposal inter alia in dryland areas. Develop and disseminate to farming households integrated farm management technologies, such as crop rotation, organic manuring and other techniques involving reduced use of agricultural chemicals, multiple techniques for sources of nutrients and the efficient utilization of external inputs, while enhancing techniques for waste and byproduct utilization and prevention of preand post-harvest losses, taking particular note of the role of women; b. Create non-farm employment opportunities through private small-scale agro-processing units, rural service centres and related infrastructural improvements; c. Promote and improve rural financial networks that utilize investment capital resources raised locally; d. Provide the essential rural infrastructure for access to agricultural inputs and services, as well as to national and local markets, and reduce food losses;. Initiate and maintain farm surveys, on-farm testing of appropriate technologies and dialogue with rural communities to identify constraints and bottlenecks and find solutions; f. Analyse and identify possibilities for economic integration of agricultural and forestry activities, as well as water and fisheries, and to take effective measures to encourage forest management and growing of trees by farmers (farm forestry) as an option for resource development. Analyse the effects of technical innovations and incentives on farm-household income and well-being; b. Initiate and maintain on-farm and off-farm programmes to collect and record indigenous knowledge. This could form the basis for technology development and exchange and for regional research collaboration. The Conference secretariat has estimated the average total annual cost (1993-2000) of implementing the activities of this programme to be about $10 billion, including about $1. Governments at the appropriate level, with the support of the relevant international and regional organizations, should strengthen research on agricultural production systems in areas with different endowments and agro-ecological zones, including comparative analysis of the intensification, diversification and different levels of external and internal inputs. Promote educational and vocational training for farmers and rural communities through formal and non-formal education; b. Launch awareness and training programmes for entrepreneurs, managers, bankers and traders in rural servicing and small-scale agro-processing techniques. Improve their organizational capacity to deal with issues related to off-farm activities and rural industry development; b. Expand credit facilities and rural infrastructure related to processing, transportation and marketing. Land-resource planning, information and education for agriculture Basis for action 14. Inappropriate and uncontrolled land uses are a major cause of degradation and depletion of land resources. Present land use often disregards the actual potentials, carrying capacities and limitations of land resources, as well as their diversity in space. The need to increase food production to meet the expanding needs of the population will put enormous pressure on all natural resources, including land. The destruction and degradation of agricultural and environmental resources is a major issue. Techniques for increasing production and conserving soil and water resources are already available but are not widely or systematically applied. A systematic approach is needed for identifying land uses and production systems that are sustainable in each land and climat e zone, including the economic, social and institutional mechanisms necessary for their implementation. To harmonize planning procedures, involve farmers in the planning process, collect landresource data, design and establish databases, define land areas of similar capability, identify resource problems and values that need to be taken into account to establish mechanisms to encourage efficient and environmentally sound use of resources; b. To establish agricultural planning bodies at national and local levels to decide priorities, channel resources and implement programmes. Establish and strengthen agricultural land-use and land-resource planning, management, education and information at national and local levels; b. Initiate and maintain district and village agricultural land-res ource planning, management and conservation groups to assist in problem identification, development of technical and management solutions, and project implementation. Collect, continuously monitor, update and disseminate information, whenever possible, on the utilization of natural resources and living conditions, climate, water and soil factors, and on land use, distribution of vegetation cover and animal species, utilization of wild plants, production systems and yields, costs and prices, and social and cultural considerations that affect agricultural and adjacent land use; b. Establish programmes to provide information, promote discussion and encourage the formation of management groups. Strengthen or establish international, regional and subregional technical working groups with specific terms of reference and budgets to promote the integrated use of land resources for agriculture, planning, data collection and diffusion of simulation models of production and information dissemination; b. Develop internationally acceptable methodologies for the establishment of databases, description of land uses and multiple goal optimization. The Conference secretariat has estimat ed the average total annual cost (1993-2000) of implementing the activities of this programme to be about $1. Develop databases and geographical information systems to store and display physical, social and economic information pertaining to agriculture, and the definition of ecological zones and development areas; b. Select combinations of land uses and production systems appropriate to land units through multiple goal optimization procedures, and strengthen delivery systems and local community participation; c. Encourage integrated planning at the watershed and landscape level to reduce soil loss and protect surface and groundwater resources from chemical pollution. Train professionals and planning groups at national, district and village levels through formal and informal instructional courses, travel and interaction; b. Generate discussion at all levels on policy, development and environmental issues related to agricultural land use and management, through media programmes, conferences and seminars. Establish land-resource mapping and planning units at national, district and village levels to act as focal points and links between institutions and disciplines, and between Governments and people; b. Establish or strengthen Governments and international institutions with responsibility for agricultural resource survey, management and development; rationalize and strengthen legal frameworks; and provide equipment and technical assistance. Land degradation is the most important environmental problem affecting extensive areas of land in both developed and developing countries. The problem of soil erosion is particularly acute in developing countries, while problems of salinization, waterlogging, soil pollution and loss of soil fertility are increasing in all countries. Land degradation is serious because the productivity of huge areas of land is declining just when populations are increasing rapidly and the demand on the land is growing to produce more food, fibre and fuel. Efforts to control land degradation, particularly in developing countries, have had limited success to date. Well planned, long-term national and regional land conservation and rehabilitation programmes, with strong political support and adequate funding, are now needed. While land-use planning and land zoning, combined with better land management, should provide long-term solutions, it is urgent to arrest land degradation and launch conservation and rehabilitation programmes in the most critically affected and vulnerable areas. By the year 2000, to review and initiate, as appropriate, national land-resource surveys, detailing the location, extent and severity of land degradation; b. To prepare and implement comprehensive policies and programmes leading to the reclamation of degraded lands and the conservation of areas at risk, as well as improve the general planning, management and utilization of land resources and preserve soil fertility for sustainable agricultural development. Develop and implement programmes to remove and resolve the physical, social and economic causes of land degradation, such as land tenure, appropriate trading systems and agricultural pricing structures, which lead to inappropriate land-use management; b. Provide incentives and, where appropriate and possible, resources for the participation of local communities in the planning, implementation and maintenance of their own conservation and reclamation programmes; c. Develop and implement programmes for the rehabilitation of land degraded by waterlogging and salinity; d. Develop and implement programmes for the progressive use of non-cultivated land with agricultural potential in a sustainable way. Governments, at the appropriate level, with the support of the relevant international and regional organizations, should: a. Strengthen and establish national land-resource data banks, including identification of the location, extent and severity of existing land degradation, as well as areas at risk, and evaluate the progress of the conservation and rehabilitation programmes launched in this regard; c. Collect and record information on indigenous conservation and rehabilitation practices and farming systems as a basis for research and extension programmes. The appropriate United Nations agencies, regional organizations and non-governmental organizations should: a. Develop priority conservation and rehabilitation programmes with advisory services to Governments and regional organizations; b. Establish regional and subregional networks for scientists and technicians to exchange experiences, develop joint programmes and spread successful technologies on land conservation and rehabilitation. The Conference secretariat has estimated the average total annual cost (1993-2000) of implementing the activities of this programme to be about $5 billion, including about $800 million from the international community on grant or concessional terms. Governments at the appropriate level, with the support of the relevant international and regional organizations, should help farming household communities to investigate and promote site-specific technologies and farming systems that conserve and rehabilitate land, while increasing agricultural production, including conservation tillage agroforestry, terracing and mixed cropping. Governments at the appropriate level, with the support of the relevant international and regional organizations, should train field staff and land users in indigenous and modern techniques of conservation and rehabilitation and should establish training facilities for extension staff and land users. Develop and strengthen national research institutional capacity to identify and implement effective conservation and rehabilitation practices that are appropriate to the existing socio-economic physical conditions of the land users; b. Coordinate all land conservation and rehabilitation policies, strategies and programmes with related ongoing programmes, such as national environment action plans, the Tropical Forestry Action Plan and national development programmes. This programme area is included in chapter 18 (Protection of the quality and supply of freshwater resources), programme area F. Conservation and sustainable utilization of plant genetic resources for food and sustainable agriculture Basis for action 14. Threats t o the security of these resources are growing, and efforts to conserve, develop and use genetic diversity are underfunded and understaffed. Many existing gene banks provide inadequate security and, in some instances, the loss of plant genetic diversity in gene banks is as great as it is in the field. This includes the development of measures to facilitate the conservation and use of plant genetic resources, networks of in situ conservation areas and use of tools such as ex situ collections and germ plasma banks. Subsequent action could be aimed at consolidation and efficient management of networks of in situ conservation areas and use of tools such as ex situ collections and germ plasma banks. Major gaps and weaknesses exist in the capacity of existing national and international mechanisms to assess, study, monitor and use plant genetic resources to increase food production. Existing institutional capacity, structures and programmes are generally inadequate and largely underfunded. Existing diversity in crop species is not used to the extent possible for increased food production in a sustainable way. To complete the first regeneration and safe duplication of existing ex situ collections on a world-wide basis as soon as possible; b. To collect and study plants useful for increasing food production through joint activities, including training, within the framework of networks of collaborating institutions; c. Not later than the year 2000, to adopt policies and strengthen or establish programmes for in situ on-farm and ex situ conservation and sustainable use of plant genetic resources for food and agriculture, integrated into strategies and programmes for sustainable agriculture; d. To take appropriate measures for the fair and equitable sharing of benefits and results of research and development in plant breeding between the sources and users of plant genetic resources. Governments at the appropriate level, with the support of the relevant international and regional organiz ations, should: a. Promote crop diversification in agricultural systems where appropriate, including new plants with potential value as food crops; f. Promote utilization as well as research on poorly known, but potentially useful, plants and crops, where appropriate; g. Develop strategies for networks of in situ conservation areas and use of tools such as onfarm ex situ collections, germplasm banks and related technologies; b. The Conference secretariat has estimated the average total annual cost (1993-2000) of implementing the activities of this programme to be about $600 million, including about $300 million from the international community on grant or concessional terms. Develop basic science research in such areas as plant taxonomy and phytogeography, utilizing recent developments, such as computer sciences, molecular genetics and in vitro cryopreservation; b. Develop major collaborative projects between research programmes in developed and developing countries, particularly for the enhancement of poorly known or neglected crops; c. Promote cost-effective technologies for keeping duplicate sets of ex situ collections (which can also be used by local communities); d. Develop further conservation sciences in relation to in situ conservation and technical means to link it with ex situ conservation efforts. Governments at the appropriate level and with the support of the relevant international and regional organizations should: a. Conservation and sustainable utilization of animal genetic resources for sustainable agriculture Basis for action 14.

In a related series of experimental studies birth control pills missed buy generic mircette pills, Saida and colleagues showed that inflammatory demyelinating neuropathy can be induced in experimental animals without prominent T-cell inflammation [8 birth control overdose cheap generic mircette uk,9 birth control pills yes or no purchase mircette,10] birth control for excessive bleeding purchase mircette canada. In their studies birth control 4 walmart cheap mircette 15 mcg visa, rabbits immunized with galactocerborside (GalC) developed anti-GalC antibody-mediated demyelinating neuropathy birth control 999 effective cheap mircette uk, which was complement dependent. Notably, macrophage recruitment and macrophage-mediated myelin phagocytosis was prominent in these studies as well. The role of macrophages in experimental autoimmune neuritis induced by a P2-specific T-cell line. This Heininger study supports the hypothesis that adoptively transferred T cells interact with macrophages at amplification and effector phases in this paradigm, and thus that macrophages are key components of endoneurial inflammation that mediate myelin/nerve fibre injury. This study showed synergism between cellular and humoral autoimmune responses to produce inflammatory demyelination in peripheral nerves. The detailed pathological studies on autopsied materials in one case showed primary axonal degeneration without significant demyelination or lymphocytic inflammation. Predominant motor axonal involvement was confirmed by electrophysiology (inexcitable motor nerves) and anterior root and phrenic (motor) nerve pathology. Notably, this study directly correlated the severity of axonal injury with poor recovery. The authors opined that one mechanism for inexcitable motor nerves is an increase in the threshold of excitation of the nerve fibres due to undefined changes in Schwann cells or axonal membranes, particularly along the nodal and paranodal regions of the nerve fibre. Subsequent experimental studies support this notion of conduction failure along the nodal axolemma [17]. This small but pivotal study (based on 2 cases) wielded huge influence in this area of research. Early nodal changes in the acute motor axonal neuropathy pattern of the Guillain-Barre syndrome. The study focused on identifying early changes and establishing the sequence of those changes. By electron microscopy the earliest and mildest changes consisted of lengthening of the node of Ranvier with distortion of the paranodal myelin, and in some instances breakdown of the outermost myelin terminal loops. At this stage many nodes had overlying macrophages which extended their processes through the Schwann cell basal lamina covering the node and apposed the axolemma. At later time points macrophage processes extended beneath the myelin terminal loops and the whole macrophage entered the periaxonal space at the paranode. Macrophage processes dissected the axon from the adaxonal Schwann cell plasmalemma and the macrophages advanced into the internodal periaxonal space, where they typically surrounded a condensed-appearing axon. This association of macrophage and axons appeared to be stable for some time, and the axons subsequently underwent Wallerian-like degeneration. The internodal myelin sheath and the abaxonal Schwann cell cytoplasm remained normal. The pathologic sequence emerging from these studies is that early in the course there are only mild changes at the nodes of Ranvier, sufficient to induce paralysis; it is only later that the axons degenerate. This study suggests that macrophages are critical to the pathogenesis and injury and dysfunction of the nodal axolemma initially and of the internodal motor axons subsequently. Moreover, the nodal and axonal injury likely depends upon macrophage contact with the axons/axolemma (contact-dependent). In separate studies, the same group has demonstrated the deposition of IgG and C3d (membrane bound cleaved product of C3) at the nodes of Ranvier initially and at paranodal and internodal axolemma at later time points after the onset of the disease [20]. Whether early complement component(s) deposits at structural specializations along myelinated axons originate from circulation or adjacent microglial/macrophage cells in the endoneurium and/or perinodal and periaxonal spaces is not established. It has been shown previously that macrophage populations can synthesize and secrete various complement components. It is believed that complement activation products may provide chemotactic cues for macrophage recruitment at the nodes and periaxonal location. Proceedings of the National Academy of Sciences, 2004 In this study Yuki and colleagues report an animal model of post-infectious autoimmune neuropathy induced by immunization of rabbits with C. Whether autoantibodies against gangliosides are by themselves sufficient to induce nerve damage or require other effectors of the innate immune system was not established in this study. The presence of periaxonal macrophages in this experimental model again emphasized that axonal injury may depend on contact between axons and macrophages. A fundamental principle learned from this series of nerve crush studies was that inflammatory milieu, primarily consisting of activated FcfiRbearing macrophage/microglia, are critical mediators of Ab-mediated nerve injury. Anti-ganglioside antibodies induce nodal and axonal injury via fcgamma receptormediated inflammation. Notably, macrophages were seen adjacent to widened nodes of Ranvier at early time points. In sum, inflammatory cells in the endoneurium, particularly macrophage recruitment, is associated with early injury to the nodes of Ranvier in both demyelinating and axonal variants of the disease. Could endoneurial glia (including microglia) be activated by soluble signals diffusing from systemic immune compartment and subsequently set up endoneurial inflammation including macrophage recruitment in these situationsfi Moreover, our experimental studies in the context of anti-ganglioside antibodies and axonal injury indicate that activating FcfiRs on macrophage populations are key molecular effectors mediating nerve injury. Whether the macrophage and activating FcfiRs interactions with immune complexes formed on nerve fibres are random or other molecular signals abet in this process (such as complement activation products) acting as chemoattractants for directing the macrophages within endoneurium to specific sites along the nerve fibres remains to be established. Moreover, the kinetics and evolving phenotype(s) (pro-inflammatory, anti-inflammatory or in between these polarized states) of macrophage/microglial cells in the endoneurial compartment of intact and injured/diseased nerves are not well defined. The molecular effectors of nerve fibre injury downstream of macrophage-immune complex interactions are also not elucidated. Indeed novel strategies to deliver such therapies selectively to endoneurial compartment would be a requisite and a challenge. Serial clinical, electrophysiological, biochemical, and morphological observations. Introduction Everything we think about is predicated on the discoveries of those who thought long before us. We gathered techniques and reagents that had been previously developed and used to study neuromuscular synaptic function in experimental mouse preparations, and applied them to investigate our hypotheses. In doing so we quickly realised that pretty much everything we thought about had already been thought about by someone before us, and we were simply inching an old idea forward or nudging it sideways towards our application. An analysis of the end-plate potential recorded with an intracellular electrode, the Journal of Physiology, 1951 the ability to record and analyse the synaptic signals, i. The neuromuscular junction offers a perfect ex vivo system, and Bernard Katz used this system to work out key aspects of the quantal theory of neurotransmission [5] for which he was awarded the Nobel Prize for Physiology or Medicine in 1970 (jointly with Ulf von Euler and Julius Axelrod). Our studies on the electrophysiological effects of anti-ganglioside antibodies at neuromuscular junctions, first performed with the Miller Fisher syndrome sera in Oxford, and subsequently in Leiden, relied heavily on the classical technical and theoretical knowledge of this process provided by Katz. The measurements nowadays are obviously much more accurate and efficient due to modern digital electrophysiological equipment and data acquisition and analysis software. Journal of Neurochemistry, 1971 Three pieces of knowledge have been crucial for directing our studies: (A) that clostridial botulinum and tetanus neurotoxins exert their paralytic effects by first binding to the presynaptic membrane at neuromuscular junctions; (B) that these toxins bind complex gangliosides [6]; and (C) that gangliosides are present in high density at presynaptic membranes of neuromuscular junctions to which circulating factors have ready access because these synapses are localized outside the blood-nerve barrier. Similarly, the development of knowledge about botulinum neurotoxin binding to cholinergic nerve terminals was a longstanding process that has gradually evolved since the 1960s and still remains an interesting area for research today, particularly with the booming use of botulinum neurotoxins in medical and cosmetic applications. Specific ganglioside binding sites have now been identified on the neurotoxin molecule, as well as a mechanism of secondary binding to synaptic vesicles proteins when they become exposed to the extracellular environment during neuroexocytosis. Journal of Biomedical Science, 1999 Continuing on the toxin theme, the use of a wide range of neurotoxins has been germane to electrophysiological studies on both neuromuscular synapse and nodal function over many decades. The reference we include, rather than reverting to the primary literature (which at the time was rejected by the Journal of Physiology! The fraction, called fiBungarotoxin, has become perhaps the most applied pharmacological tool in neuromuscular junction research, and indeed has been vitally important for our work. Due to its selective blocking action on skeletal muscle type voltage-gated Na channels (Na 1. Purification from black widow spider venom of a protein factor causing the depletion of synaptic vesicles at neuromuscular junctions. Journal of Cell Biology, 1976 the recurring theme of toxins must include reference to the electrophysiological and morphological effects of Latrotoxin, a neurotoxic component of the venom of the black widow spider venom. Frontali and colleagues [8] purified a protein fraction from the venom that was highly toxic for mice and showed that this factor was responsible for the depletion of synaptic vesicles from motor nerve terminals, associated with a tremendous increase in the frequency of miniature endplate potentials, shown before by others with the whole venom. The similarity between the effects of this Latrotoxin and the action of anti-ganglioside autoantibody containing the Miller Fisher syndrome sera (and later, acute motor axonal neuropathy sera as well as corresponding anti-ganglioside monoclonal antibodies generated by us) in the presence of complement activation is remarkable. It allowed us to build up a model of presynaptic membrane injury resulting from 2+ pore formation with aberrant Ca influx. The electron micrographs of nerve terminals are virtually identical between the 2 conditions, i. Clearly this especially refers to the complement-fixing immunoglobulin isotypes and subclasses, notably IgM and IgG1-3. In parallel, the basic biology of the complement system has been elucidated in great detail and there is no better place to focus attention than on the formation of membrane attack complex [9]. This is a self-assembling transmembrane complex that becomes deposited in plasma membranes targeted by complement-fixing autoantibodies. In an autoimmune situation, at nerve membranes in particular, it appears to be highly toxic, disturbing the ionic balance between intraand extracellular compartments and maintenance of the resting membrane potential. In this review paper, Podack and Tschopp presented beautiful ultrastructural images and a model of this process that greatly helped us understand the relationship between membrane attack complex and the pore-forming Latrotoxin. In our studies, immunostaining clearly showed the presence of membrane attack complex at mouse motor nerve terminals in nerve-muscle preparations that had been treated with anti-ganglioside antibodies and added human serum as a source of complement. Along with Niels Jerne, Kohler and Milstein were awarded a Nobel Prize in 1984 for the discovery of this principle of antibody production. The ability to accurately apply fixed concentrations of known monoclonal antibodies with known ganglioside binding patterns in unlimited supply, compared with scarce human sera with less well-defined properties, has been a cornerstone of our lab activities. Indeed, without these monoclonal antibodies we would not have succeeded in further understanding our subject area beyond the simplest of points. Proceedings of the National Academy of Sciences of the United States of America, 1996 the development of transgenic mice that lack glycosyltransferases involved in ganglioside biosynthesis has allowed researchers to uncover hitherto unknown functions of gangliosides. Despite prior suggestions that complex gangliosides were key components of the presynaptic apparatus, it turned out that gangliosides are remarkably redundant in supporting neurotransmitter release at the neuromuscular junction. This indicates that gangliosides are not absolutely required for neurotransmitter release. Nevertheless, the ability to manipulate ganglioside content and levels in presynaptic membranes provided key insights into the binding and subsequent action of anti-ganglioside antibodies. Cancer Research, 1992 Monoclonal antibodies targeted against tumour cell-specific antigens have long been considered to be magic bullets for therapy development. The Journal of Neuroscience, 1986 the presynaptic membrane of motor nerve terminals is not static, but exists in a highly dynamic state due to the continuous addition and removal of membrane surface due to the processes of synaptic vesicle exocytosis and endocytosis, respectively. One issue that always intrigued us has been the fate of antibody landing on this surface. How long is it held there and does this provide sufficient time for activation of the complement cascadefi The papers by Fabian and colleagues provided constant interest whilst we were studying this field, making us realise that the motor nerve terminal was a highly dynamic structure with very rapid rates of membrane turnover [13]. Is it then recycled to the plasma membrane or destined for a retrograde trafficking pathwayfi This remains an area of great interest, almost 30 years after this beautiful paper was published, and a constant source of inspiration that also undermines any idle preconceptions one might hold. Perhaps most importantly, we each also gained a highly trusted and lifelong friend. Fatt P, Katz B (1951) An analysis of the end-plate potential recorded with an intracellular electrode. Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Takamiya K, Yamamoto A, Furukawa K, Yamashiro S, Shin M, Okada M, Fukumoto S, Haraguchi M, Takeda N, Fujimura K, et al. Since their discovery in the late 1930s, these cell surface receptors have been shown to be essential components of not only the nervous system, but also of almost all cells and tissues of the body. Klenk was the first researcher to describe gangliosides, which he isolated from the organs of patients with NiemannPick and Tay-Sachs disease [1], but his work was reinforced by that of a Swedish researcher named Gunnar Blix, who was the first person to identify sialic acid [2].

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