Significant reduction in hemarthrosis in boys with severe hemophilia A: The China hemophilia individualized low-dose secondary prophylaxis study.

INTRODUCTION: In countries with restricted access to clotting factor concentrates, early implementation of low-dose prophylaxis is recommended over episodic treatment. OBJECTIVE: The objective of this 1-year prospective secondary prophylaxis study was to evaluate the efficacy of a dose/frequency escalating protocol in young boys with hemophilia A in China. METHODS: Boys were started on a low-dose protocol (minimum 10-15 IU/kg of factor VIII [FVIII] twice weekly). Escalation was based on index joint bleeding, swelling/persistent joint swelling, and serial ultrasound (gray scale and color Doppler) examinations of index joints. RESULTS: Thirty-three boys, median age 4.8 years (interquartile range, 3.8-6.1) were enrolled in a 3-month observation period that preceded a 1-year prophylaxis phase. A significant reduction in total bleeding events (43.0%, P = .001), index joint bleeds (53.2%, P = .002), and target index joint bleeds (70.0%, P = 0.02) was observed during the prophylaxis phase. During the prophylaxis period, 40% of target joints resolved. The percentage of boys with zero index joint bleeds increased significantly (P = .004) from 51.5% during the observation phase to 81.8% in last quarter of the prophylaxis phase (months 10-12). There was no progression of arthropathy based on physical examination (Hemophilia Joint Health Score), X-ray, and ultrasound obtained at entry into the prophylaxis phase and at study exit. The median FVIII consumption over the prophylaxis phase was 1786 IU/kg/y. CONCLUSION: A low-dose, individualized prophylaxis protocol, guided by individual bleeding profiles and serial assessment of joint status, enables escalation of treatment intensity in boys with severe hemophilia A, leading to a significant reduction in bleeding events and reduction in target joint bleeding.

Musculoskeletal ultrasound in hemophilia: Results and recommendations from a global survey and consensus meeting.

INTRODUCTION: For persons with hemophilia, optimization of joint outcomes is an important unmet need. The aim of this initiative was to determine use of ultrasound in evaluating arthropathy in persons with hemophilia, and to move toward consensus among hemophilia care providers regarding the preferred ultrasound protocols for global adaptation. METHODS: A global survey of hemophilia treatment centers was conducted that focused on understanding how and why ultrasound was being used and endeavored to move toward consensus definitions of both point-of-care musculoskeletal ultrasound (POC-MSKUS) and full diagnostic ultrasound, terminology to describe structures being assessed by ultrasound, and how these assessments should be interpreted. Next, an in-person meeting of an international group of hemophilia health care professionals and patient representatives was held, with the objective of achieving consensus regarding the acquisition and interpretation of POC-MSKUS and full diagnostic ultrasound for use in the assessment of musculoskeletal (MSK) pathologies in persons with hemophilia. RESULTS: The recommendations were that clear definitions of the types of ultrasound examinations should be adopted and that a standardized ultrasound scoring/measurement system should be developed, tested, and implemented. The scoring/measurement system should be tiered to allow for a range of complexity yet maintain the ability for comparison across levels. CONCLUSION: Ultrasound is an evolving technology increasingly used for the assessment of MSK outcomes in persons with hemophilia. As adoption increases globally for clinical care and research, it will become increasingly important to establish clear guidelines for image acquisition, interpretation, and reporting to ensure accuracy, consistency, and comparability across groups.

Intraspecific variability of cell reaggregation during reproduction cycle in sponges.

The ability of sponge cells to reaggregate and reconstruct intact functional organism is known for more than 100 years. This process was studied in numerous species of sponges, and its interspecific variability is well described. However, some data also indicate the existence of a certain intraspecific variability of the cell reaggregation. The present study deals with the cell reaggregation in two demosponges, Halichondria panicea and Halisarca dujardinii, during different periods of their sexual reproduction. In both species, cell reaggregation shows a common pattern at all studied periods of reproduction. However, the course of the reaggregation process significantly depends on the reproduction period of an individual used in the experiment, thus demonstrating pronounced intraspecific variability, which concerns the rate of the cell reaggregation and the final stage of the process. This variability occurs due to tissue rearrangements that accompany reproduction and changes cell composition and amount of available somatic stem cells in sponge tissues, and consequently alters morphogenetic potencies of a cell suspension and multicellular aggregates. In both Halichondria panicea and Halisarca dujardinii, the growth period is the most favorable for the reaggregation process, while the cell reaggregation is depressed during periods of embryogenesis and restoration of somatic tissues after the reproduction. At the same time, the structure of a particular stage of reaggregation and morphogenetic processes underlying the development of multicellular aggregates are always identical, independently from the period of the reproductive cycle.

Use of ultrasound for assessment of musculoskeletal disease in persons with haemophilia: Results of an International Prophylaxis Study Group global survey.

AIM: The objective of this survey was to understand the global trends of imaging assessments in persons with haemophilia, focusing on point-of-care ultrasound (POCUS). Insights into the barriers impeding its widespread proliferation as a frontline imaging modality were obtained. METHODS: The survey opened in September of 2017 and closed in May of 2018. Haemophilia Treatment Centres (HTCs) treating both paediatric/adult patients were the population of interest. A REDCap survey of 25 questions was disseminated to 232 clinical staff in 26 countries. RESULTS: The majority of respondents (88.3%, 91/103) reported that POCUS is most useful to confirm or rule out a presumed acute joint bleed. European HTCs reported the highest routine use of POCUS at 59.5% (22/37) followed by HTCs in the "Other" countries of the world at 46.7% (7/15) and North American HTCs at 43.9% (25/57). At the time of the survey, physiotherapists were identified as the clinical staff who perform POCUS 52.8% (28/53) of the time, in contrast with nurses/nurse practitioners who represent only 5.7% (3/53) of users. The greatest perceived barriers to the implementation of POCUS are the lack of trained healthcare professionals who can perform POCUS at 69.2% (74/107) and the overall time commitment required at 68.2% (73/107). CONCLUSION: Despite POCUS being used in 49.5% (54/109) of sampled HTCs, it is still utilized almost 30% less globally than full diagnostic ultrasound. A list of barriers has been identified to inform HTCs which challenges they will likely need to overcome should they choose to incorporate this imaging modality into their practice.

Transdifferentiation and mesenchymal-to-epithelial transition during regeneration in Demospongiae (Porifera).

Origin and early evolution of regeneration mechanisms remain among the most pressing questions in animal regeneration biology. Porifera have exceptional regenerative capacities and, as early Metazoan lineage, are a promising model for studying evolutionary aspects of regeneration. Here, we focus on reparative regeneration of the body wall in the Mediterranean demosponge Aplysina cavernicola. The epithelialization of the wound surface is completed within 2 days, and the wound is completely healed within 2 weeks. The regeneration is accompanied with the formation of a mass of undifferentiated cells (blastema), which consists of archaeocytes, dedifferentiated choanocytes, anucleated amoebocytes, and differentiated spherulous cells. The main mechanisms of A. cavernicola regeneration are cell dedifferentiation with active migration and subsequent redifferentiation or transdifferentiation of polypotent cells through the mesenchymal-to-epithelial transformation. The main cell sources of the regeneration are archaeocytes and choanocytes. At early stages of the regeneration, the blastema almost devoid of cell proliferation, but after 24 hr postoperation (hpo) and up to 72 hpo numerous DNA-synthesizing cells appear there. In contrast to intact tissues, where vast majority of DNA-synthesizing cells are choanocytes, all 5-ethynyl-2'-deoxyuridine-labeled cells in the blastema are mesohyl cells. Intact tissues, distant from the wound, retains intact level of cell proliferation during whole regeneration process. For the first time, the apoptosis was studied during the regeneration of sponges. Two waves of apoptosis were detected during A. cavernicola regeneration: The first wave at 6-12 hpo and the second wave at 48-72 hpo.

Journey of the Human Papillomavirus (HPV) in a Developing Country over 5 Years (2010 - 2015).

Human papillomavirus (HPV) is a prevalent sexually transmitted infection with serious medical, sexual, and relationship consequences. HPV vaccine protection is available globally but unfortunately vaccine uptake is inconsistent everywhere. From this study, it was observed that the awareness of cervical cancer, HPV virus and HPV vaccination in Malaysia is high, at 83.1%, 73.9% and 73.3% of respondents, respectively. However, a considerably low percentage had undergone HPV vaccination (8.6%) compared to those who had experienced a Pap smear (32.9%). Awareness between cervical cancer and HPV virus and vaccination was low. Health care providers and the governing bodies have to play a vital role in disseminating holistic information on the vaccine and the importance of getting vaccinated to the public more vigorously in Malaysia.

The value of usability testing for Internet-based adolescent self-management interventions: "Managing Hemophilia Online".

BACKGROUND: As adolescents with hemophilia approach adulthood, they are expected to assume responsibility for their disease management. A bilingual (English and French) Internet-based self-management program, "Teens Taking Charge: Managing Hemophilia Online," was developed to support adolescents with hemophilia in this transition. This study explored the usability of the website and resulted in refinement of the prototype. METHODS: A purposive sample (n=18; age 13-18; mean age 15.5 years) was recruited from two tertiary care centers to assess the usability of the program in English and French. Qualitative observations using a "think aloud" usability testing method and semi-structured interviews were conducted in four iterative cycles, with changes to the prototype made as necessary following each cycle. This study was approved by research ethics boards at each site. RESULTS: Teens responded positively to the content and appearance of the website and felt that it was easy to navigate and understand. The multimedia components (videos, animations, quizzes) were felt to enrich the experience. Changes to the presentation of content and the website user-interface were made after the first, second and third cycles of testing in English. Cycle four did not result in any further changes. CONCLUSIONS: Overall, teens found the website to be easy to use. Usability testing identified end-user concerns that informed improvements to the program. Usability testing is a crucial step in the development of Internet-based self-management programs to ensure information is delivered in a manner that is accessible and understood by users.

Mobility of O+ in He and interaction potential of HeO+.

New experimental measurements are reported for the mobility of O(+) ions in He gas at 300 K. The accuracy of these new values is estimated as +/-2.5%, which allows them to serve as a stringent test of a new ab initio potential that we have calculated using the RCCSD(T) method. We employed the aug-cc-pV5Z basis set with counterpoise corrections and took spin-orbit coupling into account. The present experimental values lie below the calculated ones, but the difference becomes statistically significant only at moderate and high values of the ratio of the electric field strength to the gas number density; even there they are only marginally significant.

Kikuchi histiocytic necrotizing lymphadenitis: clinicopathological and immunohistochemical study.

Clinical, morphological and immunohistochemical features of 10 cases having the lymphnodal histological pattern of Kikuchi disease were examined. Two of these were diagnosed as systemic lupus erythematosus (SLE). Morphologically, Kikuchi disease and SLE were nearly indistinguishable. Plasma cells, neutrophilic infiltration, haematoxyphilic bodies and vasculitis were not useful in differentiating the conditions. Kikuchi lymphadenitis and malignant lymphoma however could be differentiated histologically. Morphological features that exclude malignancy included: polymorphous nature of cellular infiltrate, absence of abnormal mitosis, preservation of sinusoidal pattern on intervening areas and presence of extracellular and intracellular karyorrhectic debris.

Kikuchi histiocytic necrotizing lymphadenitis: clinicopathological and immunohistochemical study

Clinical, morphological and immunohistochemical features of 10 cases having the lymphnodal histological pattern of Kikuchi disease were examined. Two of these were diagnosed as systemic lupus erythematosus [SLE]. Morphologically, Kikuchi disease and SLE were nearly indistinguishable. Plasma cells, neutrophilic infiltration, haematoxyphilic bodies and vasculitis were not useful in differentiating the conditions. Kikuchi lymphadenitis and malignant lymphoma however could be differentiated histologically. Morphological features that exclude malignancy included: polymorphous nature of cellular infiltrate, absence of abnormal mitosis, preservation of sinusoidal pattern on intervening areas and presence of extracellular and intracellular karyorrhectic debris

The outcome of a 2-week treatment of Helicobacter pylori-positive duodenal ulcer with omeprazole-based antibiotic regimen in a region with high metronidazole resistance rate.

BACKGROUND/OBJECTIVE: Metronidazole resistance is a major problem in many developing countries. Our main objective was to study the outcome of a non-metronidazole and omeprazole-based antibiotic regimen in eradicating Helicobacter pylori in patients with duodenal ulcer. DESIGN: A prospective study of 50 consecutive patients with proven peptic ulcer (mean age 36.6 +/- 10.5 years, range 17-60, male:female = 2), referred from the primary health centres. MAIN OUTCOME MEASURE: The primary outcome of the study was H. pylori eradication, at least 4 weeks after stopping antibiotic treatment. METHODS: Patients were considered eligible for the study if they had endoscopic evidence or a past medical history of peptic ulcer and had not received any antibiotics for at least 4 weeks prior to admission into the study. H. pylori infection was confirmed by serology, histology, a rapid urease test (RUT) and culture. After an initial oesophago-gastroduodenoscopy (OGD), each patient received a 2-week course of omeprazole (20 mg twice daily), and each of amoxycillin capsules (500 mg) and clarithromycin tablets (250 mg) thrice daily after food. The follow-up OGDs were performed after a mean period of 10.04 weeks (range 4-48) and at 10.4 +/- 2.5 months (range 6-14 months) after stopping treatment. RESULTS: All 50 patients completed the study. The sensitivity values for serology, RUT and histopathology were 98, 96 and 100%, respectively. H. pylori culture was positive in only 15 of 50 patients (30% sensitivity). H. pylori was eradicated in 47 (94%) patients. There was no evidence of H. pylori infection in the 27 of 35 (77%) patients, who returned for a third OGD. At the time of the second OGD, there was a significant reduction of pain-days (from 5.47 to 1.16), and antral (from 1.95 to 0.78) and corpus (from 1.8 to 0.6) mucosal cellular infiltrate scores, when compared with the first OGD (P < 0.001 in each case). CONCLUSION: Exclusion of metronidazole from the treatment regimen of patients with H. pylori-positive duodenal ulcer in a region with metronidazole resistance yielded an excellent H. pylori eradication rate of 94%, when omeprazole, amoxicillin and clarithromycin were used.

The relationship between hepatitis C virus and schistosomiasis: histopathologic evaluation of liver biopsy specimens.

The reported high incidence of anti-HCV seropositivity in the Egyptian population seems surprising. Some suggest that schistosomiasis is the responsible factor, either by producing false positivity for HCV antibodies or by predisposing to actual HCV infection in some way. In an attempt to investigate this unclear relationship on a histological level, we performed a thorough semiquantitative morphological study of liver biopsy specimens from 44 anti-HCV-positive Egyptian patients with chronic liver disease. More than half of these patients (23) had serological evidence of schistosomiasis. The results have shown that all 44 liver biopsy specimens demonstrated the histopathological features known to be characteristic of chronic HCV hepatitis. Statistical analysis showed no significant difference between the schistosomal and nonschistosomal groups regarding the semiquantitative histological scores of these features. This study confirms the presence of definite HCV-induced hepatic pathology in all anti-HCV seropositive cases. More importantly, it shows the lack of enhancement of this pathology in the schistosomal patients.