We recently reported that the aldehyde residue of an abasic (Ap) site in duplex DNA can generate an interstrand cross-link via reaction with a guanine residue on the opposing strand. This finding is intriguing because the highly deleterious nature of interstrand cross-links suggests that even small amounts of Ap-derived cross-links could make a significant contribution to the biological consequences stemming from the generation of Ap sites in cellular DNA. Incubation of 21-bp duplexes containing a central 5'-CAp sequence under conditions of reductive amination (NaCNBH(3), pH 5.2) generated much higher yields of cross-linked DNA than reported previously. At pH 7, in the absence of reducing agents, these Ap-containing duplexes also produced cross-linked duplexes that were readily detected on denaturing polyacrylamide gels. Cross-link formation was not highly sensitive to reaction conditions, and the cross-link, once formed, was stable to a variety of workup conditions. Results of multiple experiments including MALDI-TOF mass spectrometry, gel mobility, methoxyamine capping of the Ap aldehyde, inosine-for-guanine replacement, hydroxyl radical footprinting, and LC-MS/MS were consistent with a cross-linking mechanism involving reversible reaction of the Ap aldehyde residue with the N(2)-amino group of the opposing guanine residue in 5'-CAp sequences to generate hemiaminal, imine, or cyclic hemiaminal cross-links (7-10) that were irreversibly converted under conditions of reductive amination (NaCNBH(3)/pH 5.2) to a stable amine linkage. Further support for the importance of the exocyclic N(2)-amino group in this reaction was provided by an experiment showing that installation of a 2-aminopurine-thymine base pair at the cross-linking site produced high yields (15-30%) of a cross-linked duplex at neutral pH, in the absence of NaCNBH(3).

We report on the 1st case of ischemic priapism secondary to poorly controlled homocystinuria. Homocystinuria is a rare, autosomal recessive, inherited disorder of metabolism that is caused by a deficiency of cystathionine synthase, leading to marked hyperhomocysteinemia. Arterial and/or venous thromboemboli are a major cause of mortality and morbidity in patients with homocystinuria. Untreated patients have a 50% chance of having a vascular event by 30 years of age. Increased homocysteine levels have been reported to upregulate prothrombotic factors and downregulate antithrombotic factors; in particular, increased homocystinuria has been found to downregulate nitric oxide (NO). Mice that are deficient in NO synthase in the cavernosal smooth muscles have a higher incidence of priapism. Decrease in NO synthase causes downregulation of cyclic guanosine monophosphate, phosphodiesterase type 5A, and Rho A/Rho-kinase. Because persistently increased homocysteine also downregulates NO, a similar mechanism could be proposed for priapism secondary to homocystinuria. In patients presenting with priapism, specific features of homocystinuria should be sought; in selected patients, screening with plasma total homocysteine might be appropriate. Ischemic priapism secondary to homocystinuria appears to respond well to the standard treatment options of aspiration, intracavernosal injection with phenylephrine, and, if required, a shunting procedure. Johnson M, Murphy E, Raheem A, Ralph D. Poorly Controlled Homocystinuria: A Rare Cause of Ischemic Priapism? Sex Med 2018;6:171-173.

OBJECTIVES: Total annual costs for syncope-related hospitalizations were $2.4 billion in 2000. The aim of this study was to examine the type and number of tests ordered for patients admitted with syncope and whether these tests helped establish the cause.

METHODS: We studied the records of 1038 patients coded as "syncope" in billing records, and 167 fulfilled the eligibility criteria. The main outcome measures were the diagnostic yield of the ordered tests, the incremental cost/incremental benefit, and the number of admissions that can be averted if risk stratification were used in the evaluation.

RESULTS: The etiology of the syncope was identified in 48.3% of the patients. Postural blood pressure measurement has the highest diagnostic yield at 58.7%, whereas history taking diagnosed 19.7% of cases. The diagnostic yields of telemetry, electrocardiogram, radionuclide stress test, echocardiography, and troponin measurement were 4.76%, 4.24%, 3.44%, 0.94%, and 0.62%, respectively. Chest x-ray, carotid ultrasonography, 24-hour Holter monitoring, brain computed tomography, and brain magnetic resonance imaging did not yield the diagnosis in any of the patients. Only 1.9% of the money spent in the evaluation of syncope was effective in leading to a definitive diagnosis. The orthostatic blood pressure measurement was ranked first in the incremental cost/incremental benefit ratio and the radionuclide stress test was ranked last (17.03 vs 42,369.0, respectively). Approximately 6% of the patients did not meet the admission criteria.

CONCLUSIONS: Physicians ordered unnecessary tests that have a low yield and are not cost-effective. A standardized algorithmic approach should be the cornerstone in the evaluation of syncope.

We recently reported that the aldehyde residue of an abasic (Ap) site in duplex DNA can generate an interstrand cross-link via reaction with a guanine residue on the opposing strand. This finding is intriguing because the highly deleterious nature of interstrand cross-links suggests that even small amounts of Ap-derived cross-links could make a significant contribution to the biological consequences stemming from the generation of Ap sites in cellular DNA. Incubation of 21-bp duplexes containing a central 5′-CAp sequence under conditions of reductive amination (NaCNBH3, pH 5.2) generated much higher yields of cross-linked DNA than reported previously. At pH 7, in the absence of reducing agents, these Ap-containing duplexes also produced cross-linked duplexes that were readily detected on denaturing polyacrylamide gels. Cross-link formation was not highly sensitive to reaction conditions, and the cross-link, once formed, was stable to a variety of workup conditions. Results of multiple experiments including MALDI-TOF mass spectrometry, gel mobility, methoxyamine capping of the Ap aldehyde, inosine-for-guanine replacement, hydroxyl radical footprinting, and LC–MS/MS were consistent with a cross-linking mechanism involving reversible reaction of the Ap aldehyde residue with the N2-amino group of the opposing guanine residue in 5′-CAp sequences to generate hemiaminal, imine, or cyclic hemiaminal cross-links (7–10) that were irreversibly converted under conditions of reductive amination (NaCNBH3/pH 5.2) to a stable amine linkage. Further support for the importance of the exocyclic N2-amino group in this reaction was provided by an experiment showing that installation of a 2-aminopurine-thymine base pair at the cross-linking site produced high yields (15–30%) of a cross-linked duplex at neutral pH, in the absence of NaCNBH3.

OBJECTIVES: Total annual costs for syncope-related hospitalizations were $2.4 billion in 2000. The aim of this study was to examine the type and number of tests ordered for patients admitted with syncope and whether these tests helped establish the cause.

METHODS: We studied the records of 1038 patients coded as "syncope" in billing records, and 167 fulfilled the eligibility criteria. The main outcome measures were the diagnostic yield of the ordered tests, the incremental cost/incremental benefit, and the number of admissions that can be averted if risk stratification were used in the evaluation.

RESULTS: The etiology of the syncope was identified in 48.3% of the patients. Postural blood pressure measurement has the highest diagnostic yield at 58.7%, whereas history taking diagnosed 19.7% of cases. The diagnostic yields of telemetry, electrocardiogram, radionuclide stress test, echocardiography, and troponin measurement were 4.76%, 4.24%, 3.44%, 0.94%, and 0.62%, respectively. Chest x-ray, carotid ultrasonography, 24-hour Holter monitoring, brain computed tomography, and brain magnetic resonance imaging did not yield the diagnosis in any of the patients. Only 1.9% of the money spent in the evaluation of syncope was effective in leading to a definitive diagnosis. The orthostatic blood pressure measurement was ranked first in the incremental cost/incremental benefit ratio and the radionuclide stress test was ranked last (17.03 vs 42,369.0, respectively). Approximately 6% of the patients did not meet the admission criteria.

CONCLUSIONS: Physicians ordered unnecessary tests that have a low yield and are not cost-effective. A standardized algorithmic approach should be the cornerstone in the evaluation of syncope.

Aim/Background: This study aims to assess the level of Breast cancer (BC) screening awareness among Egyptian females with correlation of being a relative of breast cancer patient, and assess possible obstacles to participate in screening programs. Methods: A 45- question survey, based on the modified Arabic version of the Breast Cancer Awareness Measure (CAM) version 2.1, was introduced to 240 relatives of Egyptian BC females (arm A) and compared to 240 Egyptian females in control group who are not relatives of BC patients (arm B). The questionnaire collected data about their knowledge of BC warning signs, risk factors, screening methods and possible obstacles. Results: Of the 472 respondents, 41% and 42.5% in arm A and B respectively were aware that there are factors could increase the risk of BC. Study arms showed slight difference in awareness level of the relation between age, family history of BC, prior history of benign beast problems, contraception, radiation exposure, high breast density, early menarche and late menopause as risk factors. However, 52.2% and 43% consider lactation as a protective factor in arm A and B respectivelyAbout 51% and 54% were aware of BC screening in arm A and B respectively. Moreover, 47% and 42.5% in arm A and B respectively were aware of methods of BC screening and 38.8%, 33.8% knew how to do Breast Self-Examination (BSE). Nevertheless, about 92.7%, 93.8% had never had a mammogram before. Only 19.4% and 18.8% performed regular BSE in arm A and B respectively. The most important barriers were not knowing the importance of the test (62.3%), fear (31%), negligence (10%) and the cost of conducting it (9%). only 18.5%, 28.9% and 31% of arm A have the intention to do SBE, CBE and mammography respectivelyin contrastto12%, 25%%and 27 % of arm B respectively. Conclusions: The level of awareness of breast cancer and breast self-examination is still low and need more effort to prevent advanced BC presentation.

RATIONALE: Stroke is a major cause of long-term adult disability with many survivors living in the community relying on family members for on-going support. However, reports of inadequate understanding of rehabilitation techniques are common. A self-management DVD-based observational learning tool may help improve functional outcomes for survivors of stroke and reduce caregivers' burden.

AIMS: This article describes the methodology of the stroke self-management rehabilitation trial. The overall aim of this pilot trial is to assess the feasibility and preliminary efficacy of a DVD-based intervention for improving functional outcomes of survivors of stroke 2 months postrandomization to inform the design of a full-scale randomized clinical trial.

DESIGN: Recruitment of a minimum of 20 survivors of stroke and their informal caregivers (where available) in each of the participating centers will occur across multiple international sites. After baseline assessments, participants will be randomly assigned to an intervention or standard care group. The intervention comprises a structured DVD observation and practice schedule over 8 weeks. All participants will complete follow-up assessments.

STUDY OUTCOMES: The outcome measures will include a global shift in the Rankin Scale scores and dichotomized scores, changes in quality of life, general health, depression, and caregiver burden at 2 months postrandomization. A qualitative analysis of the effects of the intervention will also be undertaken.

DISCUSSION: The results of the pilot study will provide knowledge of whether observational learning techniques delivered via DVD can effectively improve recovery after stroke and reduce caregiver burden.