Letter to the Editor Regarding: Evolving Business Models in Orthotics by Schneider, N.

The purpose of this letter is to continue the dialogue regarding the paper "Evolving business models in Orthotics" in the Canadian Prosthetics & Orthotics Journal Volume 4, Issue2, No.3, 2021. In it we present the perspective of the current Alberta Association of Orthotists and Prosthetists (AAOP) and provide additional context and information on historical events. Finally, we provide additional clarity on how costing is approached in the Province of Alberta (Canada) and the purported inequity in compensation between the two disciplines.

Manejo nutricional de ascitis quilosa: Serie de casos y revisión de la literatura

RESUMEN Las ascitis quilosa (AQ) es una entidad poco común producida por el acúmulo de linfa en la cavidad peritoneal. Su incidencia se describe en aumento progresivo, asociándose a una mortalidad de 40-70%. Se incluyeron 3 pacientes con diagnóstico de AQ evaluados en la visita de asistencia nutricional del Hospital Clínico de la Universidad Católica (UC) durante el año 2019. Caso 1: Paciente mujer de 47 años, consulta por dolor abdominal agudo realizándose apendicectomía. Estudio de líquido peritoneal con triglicéridos (TG) de 1.362 mg/dL. Inicia Nutrición Parenteral Total (NPTC) progresando luego a régimen oral. Estudio no revela lesiones de vasos linfáticos ni otras causas. Caso 2: Paciente varón de 68 años con cirrosis por alcohol, Child Pugh B. Ingresa por disnea y ascitis refractaria. Estudio de líquido ascítico y pleural, con TG de 439 mg/dL y 592 mg/dL respectivamente. Se manejó con toracocentesis y paracentesis evacuadoras, tratamiento con régimen hipograso y aporte de triglicéridos de cadena media (MCT) vía oral. Evolución tórpida requiriendo apoyo con NPTC, realizándose drenajes sucesivos, por lo que se instala TIPS. Caso 3: Paciente mujer de 63 años consulta por dolor hipogástrico con masa palpable subcostal derecha. Estudio confirma masa pancreática por lo que se realiza Whipple. Reingresa por náuseas y vómitos profusos, evidenciándose líquido ascítico con TG de 251 mg/dl. Se inicia NPTC, escasos débitos del drenaje iniciándose realimentación progresiva por vía oral. El análisis del líquido tras la paracentesis establece el diagnóstico de AQ pues la clínica es inespecífica. Las principales complicaciones están dadas por la pérdida de quilo: desnutrición, infecciones y sepsis. Las opciones de tratamiento incluyen: medidas dietéticas, fármacos e intervenciones percutáneas o quirúrgicas; siempre orientadas al alivio sintomático, con foco en tratar la causa. Si la tolerancia oral es óptima la primera medida es la supresión de la grasa y la suplementación con MCT para evitar déficit energético. Con el empleo de estas medidas se ha reportado el cierre espontáneo de fístulas y/o defectos de vasos linfáticos en un 75%-80%. Se concluye que no hay guías de recomendación y los estudios se basan en series de pocos casos clínicos. La ascitis quilosa es una entidad patológica rara, que representa una situación clínica crítica con consecuencias inmunológicas y nutricionales; y el tratamiento debe ser etiológico y el paso clave inicial es optimizar el estado nutricional del paciente.

ABSTRACT Chylous ascites (CA) is an uncommon entity caused by the accumulation of lymph in the peritoneal cavity, its incidence has been gradually increasing; being associated with a mortality of 40-70%. This work includes 3 patients with CA diagnosis evaluated by the Nutritional Assistance team in the Hospital Clínico of the Universidad Católica, Chile during 2019. Case 1: 47-year-old female, with acute abdominal pain that resulted in an appendectomy. Peritoneal fluid study showed triglycerides (TG) of 1362 mg/dL. Total Parenteral Nutrition (TPN) was initiated with successive changes to an oral regimen. The case was negative for lymphatic vessel injuries or other causes of AQ. Case 2: 68-year-old male with alcoholic cirrhosis, Child-Pugh B. The patient was admitted for dyspnea and refractory ascites. Ascites and pleural fluid study showed TG of 439 mg/dL and 592 mg/dL, respectively, whichwas managed with thoracentesis and evacuating paracentesis, treatment with a low-fat regimen, and oral medium chain triglycerides (MCT). Case 2 had a poor evolution requiring TPN and successive evacuations, with TIPS installed. Case 3: A 63-year-old female patient with hypogastric pain and palpable right subcostal mass. Study confirmed a pancreatic tumor and Whipple Surgery was performed. Case 3 was readmitted for nausea and vomiting, showing ascitic fluid with TG of 251 mg/dl. TPN was started, with decrease in drainage fluids and successful progressive oral refeeding. The analysis of the paracentesis fluid established the diagnosis of CA since the symptoms were nonspecific. The main complications were due to the loss of chyle: malnutrition, infections and sepsis. Treatment options included: dietary measures, drugs, and percutaneous or surgical interventions; always oriented to symptomatic relief, focused on etiologic treatment. If oral tolerance is optimal, the first measure should be fat suppression and supplementation with MCT to avoid energy deficit. With the use of these measures, spontaneous closure of fistulas and / or lymphatic vessel defects has been reported in 75% -80% of patients. There are no recommendation guidelines for CA and studies are based on series of a few clinical cases. CA is a rare disease, representing a critical clinical situation with immunological and nutritional consequences. Etiologic treatment must be prioritized with a focus on optimization of the nutritional status of the patient

Analysis of porcine body size variation using re-sequencing data of miniature and large pigs.

BACKGROUND: Domestication has led to substantial phenotypic and genetic variation in domestic animals. In pigs, the size of so called minipigs differs by one order of magnitude compared to breeds of large body size. We used biallelic SNPs identified from re-sequencing data to compare various publicly available wild and domestic populations against two minipig breeds to gain better understanding of the genetic background of the extensive body size variation. We combined two complementary measures, expected heterozygosity and the composite likelihood ratio test implemented in "SweepFinder", to identify signatures of selection in Minipigs. We intersected these sweep regions with a measure of differentiation, namely FST, to remove regions of low variation across pigs. An extraordinary large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on SNP-array data of F2 individuals from a cross of Goettingen Minipigs and large pigs. RESULTS: Selective sweep analysis identified putative sweep regions for growth and subsequent gene annotation provided a comprehensive set of putative candidate genes. A long swept haplotype on chromosome X, descending from the Goettingen Minipig founders was associated with a reduction of adult body length by 3% in F2 cross-breds. CONCLUSION: The resulting set of genes in putative sweep regions implies that the genetic background of body size variation in pigs is polygenic rather than mono- or oligogenic. Identified genes suggest alterations in metabolic functions and a possible insulin resistance to contribute to miniaturization. A size QTL located within the sweep on chromosome X, with an estimated effect of 3% on body length, is comparable to the largest known in pigs or other species. The androgen receptor AR, previously known to influence pig performance and carcass traits, is the most obvious potential candidate gene within this region.

Low medical morbidity and mortality after acute courses of electroconvulsive therapy in a population-based sample.

BACKGROUND: To determine event rates for specific medical events and mortality among individuals receiving electroconvulsive therapy (ECT). METHOD: Population-based cohort study using health administrative data of acute ECT treatments delivered in Ontario, Canada, from 2003 to 2011. We measured the following medical event rates, per 10 000 ECT treatments, up to 7 and 30 days post-treatment: stroke, seizure, acute myocardial infarction, arrhythmia, pneumonia, pulmonary embolus, deep vein thrombosis, gastrointestinal bleeding, falls, hip fracture, and mortality. RESULTS: A total of 135 831 ECT treatments were delivered to 8810 unique patients. Overall medical event rates were 9.1 and 16.8 per 10 000 ECT treatments respectively. The most common medical events were falls (2.7 and 5.5 per 10 000 ECT treatments) and pneumonia (1.8 and 3.8 per 10 000 ECT treatments). Fewer than six deaths occurred on the day of an ECT treatment. This corresponded to a mortality rate of less than 0.4 per 10 000 treatments. Deaths within 7 and 30 days of an ECT treatment, excluding deaths due to external causes (e.g., accidental and intentional causes of death), were 1.0 and 2.4 per 10 000 ECT treatments respectively. CONCLUSION: Morbidity and mortality events after ECT treatments were relatively low, supporting ECT as a low-risk medical procedure.

Liver transcriptome analysis reveals important factors involved in the metabolic adaptation of the transition cow.

During early lactation, dairy cows experience a severe metabolic load often resulting in the development of various diseases. The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. We conducted a whole-liver transcriptome analysis for the transition cow to identify novel factors crucial for metabolic adaptation. Liver samples were obtained from 6 Red Holstein dairy cows (parity 2 to 7, mean ± standard deviation: 3.7 ± 2.3) at 3 time points: T1 = 22 ± 4 d antepartum, T2 = 10 ± 2 d postpartum, and T3 = 17 ± 2 d postpartum. Using RNA sequencing (RNA-seq), we studied the transcriptomic profile of the transition cow before and after parturition. We performed a differential gene expression analysis (DGEA) and gene-set enrichment analysis (GSEA) for biological processes (gene ontology, GO) and pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG). Among the 10,186 expressed genes, we discovered 1,063 differentially expressed genes (false discovery rate = 5%). The GSEA revealed 16 biological processes and 7 pathways significantly (false discovery rate = 5%) associated with the hepatic changes of the transition cow. Our results confirm that major hepatic changes are related to energy mobilization after parturition; in particular, they are related to fatty acid oxidation/metabolism, cholesterol metabolism, and gluconeogenesis. Using the STRING database (https://string-db.org/), we investigated interactions between significant genes and identified 9 key genes (CYP7A1, APOA1, CREM, LOC522146, CYP2C87, HMGCR, FDFT1, SGLE, and CYP26A1) through which the different processes involved in the metabolic adaptation interact. Comparing our main results with the literature, we could identify further genes that have not yet been associated with the transition period (e.g., CPT1B, ADIPOR2, LEPR, CREB3L3, and CCND1) and that are mainly involved in processes controlled by AMP-activated protein kinase, an important regulator of energy homeostasis.

Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

BACKGROUND: Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. AIM: To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. METHODS: This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. RESULTS: One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. CONCLUSION: In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21).

[Early detection, negotiation and treatment of alcohol use disorders in primary care]. / Alkoholerkrankung: Früherkennung, Gesprächsführung und Behandlung im primärärztlichen Bereich.

Subjects with alcohol dependence or alcohol-related health problems frequently use the primary care system without receiving the correct diagnosis or specific interventions. Stigma, lack of knowledge and know-how with regards to diagnosis and treatment of alcohol-related disorders on the site of the health care professionals may contribute to the treatment gap. General anamnesis, clinical evaluation, and laboratory parameters can serve as indicators, and validated screening tests can further corroborate the hypothesis. However, a diagnosis should only be made according to ICD-10 criteria. Adequate counselling techniques substantially contribute to successful physician-patient interaction. Motivational Interviewing combines a positive, appreciative attitude with communicative techniques to create a motivation to change. It includes general approaches as open questions, appreciation of the patient, active listening, summarizing results as well as specific approaches such as change and confidence talk and dealing with resistance. Within a positive relationship, the conversation can lead to change. Brief interventions cover four to five sessions with a duration between five and sixty minutes. Brief interventions based on an empathic attitude und reflection of findings, a brief advice leaving the responsibility on the patient's side and supporting self-efficacy can improve alcohol-related disorders. The transtheoretical model of change may help the health care provider to adapt intervention strategies to the patient's state. Primary health care provides an adequate framework for screening, diagnosis and intervention for alcohol-related disorders with the aim of reduction or abstinence. Further institutions in addiction treatment such as self-help and clinical institutions may complement the treatment system.

Activity of the antiseptic polyhexanide against meticillin-susceptible and meticillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the most important pathogens, with increasing emergence of meticillin-resistant S. aureus (MRSA) strains. This is associated not only with multiresistance to antibiotics but also with increasing resistance to topical antibiotics and antiseptics. As the antiseptic polyhexanide has only a low risk of emergence of resistant strains, the aim of the study was to obtain data on the sensitivity of S. aureus towards polyhexanide. The effect of polyhexanide was tested against 80 meticillin-susceptible S. aureus (MSSA) and 80 MRSA strains from sporadic cases as well as against 6 MRSA outbreak strains. The clonal diversity of the 166 strains was proven by pulsed-field gel electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by the serial broth microdilution technique according to DIN 58940. Time-kill studies were performed for reference strains MSSA ATCC 29213 and MRSA ATCC 33591. MICs and MBCs in the range of 0.5-2mg/L were found. According to a created epidemiological cut-off (ECOFF) value of 4mg/L, all strains were regarded as susceptible to polyhexanide, including MRSA epidemic strains and MSSA and MRSA sporadic strains with various antibiotic susceptibility patterns. Addition of up to 4% albumin to the test medium did not change the MICs and MBCs. Time-kill studies showed reduction rates of 4log10CFU/mL for 200mg/L and 5log10CFU/mL for 400mg/L polyhexanide within 5-30min. It is concluded that polyhexanide is suitable for topical eradication of S. aureus.

Clinical trial: long-term use of proton pump inhibitors in primary care patients - a cross sectional analysis of 901 patients.

BACKGROUND: The use of proton pump inhibitors (PPIs) is extensive. While the incidence of new treatments remains stable, the prevalence of long-term treatment is rising. Studies have shown that up to 70% of patients on chronic acid suppression lack a verified indication for treatment. AIMS: To investigate primary care patient characteristics associated with long-term use of PPIs. METHODS: A cross-sectional analysis of 42,634 patients registered with 22 general practitioners was performed. Patients with prescriptions of > or =120 tablets/year were defined as long-term users. A survey of a subgroup of patients without verified indication was performed. RESULTS: In all, 901 (2.1%) patients were long-term treated. Verified indications for treatment were identified for 247/901 (27%). An upper GI endoscopy had been performed in 418 patients (46%). Of the 194/654 without verified indication who participated in the survey, 71% reported heartburn/acid regurgitation as the reason for therapy. On-demand therapy was reported by 43/194 (22%) and previous attempts to withdraw by 119/194 (61%). CONCLUSIONS: The prevalence of PPI long-term treatment among primary care patients is 2.1%. The main reason for treatment is reflux symptoms or verified GERD. Rationalization of use of PPIs is possible as daily treatment without attempts to discontinue is frequently observed.

Is amino acid racemization a useful tool for screening for ancient DNA in bone?

Many rare and valuable ancient specimens now carry the scars of ancient DNA research, as questions of population genetics and phylogeography require larger sample sets. This fuels the demand for reliable techniques to screen for DNA preservation prior to destructive sampling. Only one such technique has been widely adopted: the extent of aspartic acid racemization (AAR). The kinetics of AAR are believed to be similar to the rate of DNA depurination and therefore a good measure of the likelihood of DNA survival. Moreover, AAR analysis is only minimally destructive. We report the first comprehensive test of AAR using 91 bone and teeth samples from temperate and high-latitude sites that were analysed for DNA. While the AAR range of all specimens was low (0.02-0.17), no correlation was found between the extent of AAR and DNA amplification success. Additional heating experiments and surveys of the literature indicated that d/l Asx is low in bones until almost all the collagen is lost. This is because aspartic acid is retained in the bone within the constrained environment of the collagen triple helix, where it cannot racemize for steric reasons. Only if the helix denatures to soluble gelatin can Asx racemize readily, but this soluble gelatine is readily lost in most burial environments. We conclude that Asx d/l is not a useful screening technique for ancient DNA from bone.

Degradation of biomolecules in artificially and naturally aged teeth: implications for age estimation based on aspartic acid racemization and DNA analysis.

Postmortem teeth are the most stable structures, and can be used to gain different information (age estimation, genetic data). Over long postmortem intervals (PMI), degradation processes may alter the molecular integrity and thus affect the reliability of applied molecular methods. Whereas some knowledge on the degradation of biomolecules in bone during the PMI exists, data for teeth are lacking. In particular, the impact of degradation processes in dentine on age estimation based on aspartic acid racemization (AAR) cannot be estimated yet. Hence, the molecular stability of both collagen and DNA was analyzed systematically, and their impact on the reliability of age estimation based on AAR and genetic analyses was checked. Two hundred and ten human and 59 porcine teeth were heated (90 degrees C in water) to simulate collagen and DNA diagenesis; 14 naturally aged teeth (PMI: 3 days to 1700 years) were analyzed comparatively. Peptide patterns of cyanogen bromide (CNBr)-cleaved collagen were employed as a new approach to check the collagen integrity. In the same samples, collagen yields, amino acid compositions, AAR in different protein fractions, and DNA integrity were analyzed. In heated human and porcine teeth the collagen content declined during the heating experiment. The amino acid composition in human samples was collagen-like until 12 days of heating. In naturally aged teeth, the collagen yielded from 9.5 to 15%, and no discrepancy of amino acid composition to that of modern collagen was observed. Electrophoresis of CNBr-peptides showed an altered pattern in experimentally degraded samples from day 10 on; naturally aged collagen displayed the typical collagen pattern. AAR increased in all protein fractions with increasing duration of the heating experiment; naturally aged samples displayed a slow accumulation of AAR. DNA degraded progressively, and after 32 h of heat exposure no more DNA was detectable, whereas the amplification of nuclear and mitochondrial DNA was successful up to 48 h. STR typing was reliable up to 16 h, and sex determination up to 40 h of heat exposure. In naturally aged samples of DNA quality, yield and typing success did not correlate with PMI. The data highlight a remarkable stability of collagen dental proteins. Within relevant forensic periods a postmortem rise of AAR under normal conditions is negligible, and analyses of dental DNA has a high chance to be successful. However, after large PMI and/or extreme postmortem conditions age estimation based on AAR and genetic analyses lose their reliability.

Soft tissue removal by maceration and feeding of Dermestes sp.: impact on morphological and biomolecular analyses of dental tissues in forensic medicine.

Maceration techniques remove soft tissue by the destruction of biomolecules, but the applied techniques may also affect the morphology and the molecular integrity of the hard tissue itself. The impact of seven different techniques for soft tissue removal on morphological and biomolecular parameters of teeth and dental tissues was systematically examined. All methods tested showed significant changes in dental morphology and in the molecular integrity of DNA and the dental proteins, as revealed by aspartic acid racemisation (AAR). In forensic casework this may have severe impacts on the results of morphological methods (e.g. age estimation based on root translucency) and of biomolecular analyses (e.g. age estimation based on AAR and DNA analysis). Therefore, age estimation based on AAR should not be applied to tissue treated in such a manner, and it is recommended that teeth for analysis should be extracted before soft tissue removal. DNA in the hard tissue seems to be less susceptible to soft tissue removal than proteins, and several of the tested maceration techniques appear not to have a damaging effect on DNA. Generally, the indication for soft tissue removal demands a careful case management to avoid methodological collisions.

[Health-related quality of life in dermatologists compared to other physicians]. / Gesundheitsbezogene Lebensqualität von Dermatologen im Vergleich zu anderen Arztgruppen.

BACKGROUND: According to recent studies, there may be differences in quality of life for physicians depending on gender and field of medicine. Presently, there are hardly any data with respect to health-related quality of life in dermatologists. METHODS: Using the SF-36 Health Survey, 112 dermatologists and 113 physicians in other fields of medicine were studied in a cross-sectional study. RESULTS: Dermatologists' mental health level averaged lower than their physical health level (chi2=28.49; p<.001). The mental and physical health level were higher in female dermatologists than in their male colleagues (e.g., GH: chi2=6.15; p<.05 and MH: chi2=6.83; p<.05). These findings are the opposite of results in other medical specialists. The differences between mental and physical health dimensions on the one hand, and between women and men on the other hand, were found in all age groups. CONCLUSIONS: In comparison to other medical specialists, dermatologists differ only slightly in their health-related quality of life. Therefore, it may be advisable to implement preventive measures concerning their comparatively low mental health status.

[A patient with Gulf war syndrome. On discussion of an uncertain disease picture]. / Ein Patient mit Golfkriegssyndrom? Zur Diskussion eines unklaren Krankheitsbildes.

The Gulf War syndrome represents neurological and neuropsychological disorders in veterans of the Persian Gulf war. Until today, the various symptoms observed could not be attributed to any defined disease. As a possible cause, exposure to neurotoxic agents such as the organophosphates used during the war has been suggested by many authors. We report on a 29-year-old man who suffered from dysmnesia, disturbance of orientation, cognitive impairment, and double vision. His history revealed several front-line operations in 1990 and 1991 during the Gulf War. Physical examinations showed a complex eye-movement disturbance and a horizontal nystagmus, which was neuro-ophthalmologically confirmed. The early auditory potentials referred to a brainstem dysfunction and the cognitive disturbances correlated to changes in the late-appearing component of event-related potentials (P 300). Brain imaging with CCT, MRI, SPECT, PET, and EEG and CSF showed no pathologies. Neuropsychological tests disclosed severe cognitive impairment especially concerning memory. Three-month follow-up studies in a department of psychosomatic medicine excluded a dissociative disorder as a feature of a post-traumatic stress or a conversion disorder. This is the first case of Gulf War syndrome in Germany. We focus on an unfamiliar complication after the war. The recent literature is reviewed.

[Psychosocial predictors of metabolic instability in brittle diabetes--a multivariate time series analysis]. / Psychosoziale Prädiktoren der metabolischen Instabilität bei Brittle Diabetes. Eine multivariate Zeitreihenanalyse.

The term "brittle diabetes" denotes the unstable course of an insulin-dependent diabetes characterised by frequent hypo- or hyperglycaemic crises. The aim of this study is to demonstrate empirically how psychosocial parameters interact with metabolic instability in a paradigmatic case of juvenile brittle diabetes. By means of a structured diary study, blood sugar values, moods (SAM), body symptoms (GBB), the daily hustle and hassle, helping therapeutic alliance (HAQ) and the aspects of setting were registered. Resulting time series (112 days each) were ARIMA-analysed by a multivariate approach. It could be shown that the mean variance of daily blood sugar values as an indicator of brittleness was predicted by moods, body complaints and by a family session as setting factor (p < 0.05, for corresponding predictors). Feelings of dominance preceded an increase of blood sugar variance, whereas depressive moods, anger and body symptoms were associated with metabolic instability. A family therapy session also resulted in an increase of the mean blood sugar variance. The model accounted for almost 30% of the total variance of the dependent variable (R-square-adjusted, p < 0.0001). The potential of multivariate time-series as a means to demonstrate psychosomatic interrelations is discussed. We believe that the results may also contribute to an empirically rooted understanding of psychodynamic processes in psychosomatoses.

Extracellular matrix-derived peptide binds to alpha(v)beta(3) integrin and inhibits angiogenesis.

Angiogenesis is associated with several pathological disorders as well as with normal physiological maintenance. Components of vascular basement membrane are speculated to regulate angiogenesis in both positive and negative manner. Recently, we reported that tumstatin (the NC1 domain of alpha 3 chain of type IV collagen) and its deletion mutant tum-5 possess anti-angiogenic activity. In the present study, we confirm that the anti-angiogenic activity of tumstatin and tum-5 is independent of disulfide bond requirement. This property of tum-5 allowed us to use overlapping synthetic peptide strategy to identify peptide sequence(s) which possess anti-angiogenic activity. Among these peptides, only the T3 peptide (69-88 amino acids) and T7 peptide (74-98 amino acids) inhibited proliferation and induced apoptosis specifically in endothelial cells. The peptides, similar to tumstatin and the tum-5 domain, bind and function via alpha(v)beta(3) in an RGD-independent manner. Restoration of a disulfide bond between two cysteines within the peptide did not alter the anti-angiogenic activity. Additionally, these studies show that tumstatin peptides can inhibit proliferation of endothelial cells in the presence of vitronectin, fibronectin, and collagen I. Anti-angiogenic effect of the peptides was further confirmed in vivo using a Matrigel plug assay in C57BL/6 mice. Collectively, these experiments suggest that the anti-angiogenic activity of tumstatin is localized to a 25-amino acid region of tumstatin and it is independent of disulfide bond linkage. Structural features and potency of the tumstatin peptide make it highly feasible as a potential anti-cancer drug.