Transfusion medicine and blood banking education and training for blood establishment laboratory staff: A review of selected countries in Africa.

BACKGROUND: Avoidable human error is a significant cause of transfusion adverse events. Adequately trained, laboratory staff in blood establishments and blood banks, collectively blood facilities, are key in ensuring high-quality transfusion medicine (TM) services. Gaps in TM education and training of laboratory staff exist in most African countries. We assessed the status of the training and education of laboratory staff working in blood facilities in Africa. STUDY DESIGN AND METHODS: A cross-sectional study using a self-administered pilot-tested questionnaire was performed. The questionnaire comprised 26 questions targeting six themes. Blood facilities from 16 countries were invited to participate. Individually completed questionnaires were grouped by country and descriptive analysis performed. RESULTS: Ten blood establishments and two blood banks from eight African countries confirmed the availability of a host of training programs for laboratory staff; the majority of which were syllabus or curriculum-guided and focused on both theoretical and practical laboratory skills development. Training was usually preplanned, dependent on student and trainer availability and delivered through lecture-based classroom training as well as formal and informal on the job training. There were minimal online didactic and self-directed learning. Teaching of humanistic values appeared to be lacking. CONCLUSION: We confirmed the availability of diverse training programs across a variety of African countries. Incorporation of virtual learning platforms, rather than complete reliance on didactic, in-person training programs may improve the education reach of the existing programs. Digitalization driven by the coronavirus disease 2019 pandemic may provide an opportunity to narrow the knowledge gap in low- and middle-income countries (LMICs).

Protein-DNA complexes are the primary sources of replication fork pausing in Escherichia coli.

Replication fork pausing drives genome instability, because any loss of paused replisome activity creates a requirement for reloading of the replication machinery, a potentially mutagenic process. Despite this importance, the relative contributions to fork pausing of different replicative barriers remain unknown. We show here that Deinococcus radiodurans RecD2 helicase inactivates Escherichia coli replisomes that are paused but still functional in vitro, preventing continued fork movement upon barrier removal or bypass, but does not inactivate elongating forks. Using RecD2 to probe replisome pausing in vivo, we demonstrate that most pausing events do not lead to replisome inactivation, that transcription complexes are the primary sources of this pausing, and that an accessory replicative helicase is critical for minimizing the frequency and/or duration of replisome pauses. These findings reveal the hidden potential for replisome inactivation, and hence genome instability, inside cells. They also demonstrate that efficient chromosome duplication requires mechanisms that aid resumption of replication by paused replisomes, especially those halted by protein-DNA barriers such as transcription complexes.

Localization of an accessory helicase at the replisome is critical in sustaining efficient genome duplication.

Genome duplication requires accessory helicases to displace proteins ahead of advancing replication forks. Escherichia coli contains three helicases, Rep, UvrD and DinG, that might promote replication of protein-bound DNA. One of these helicases, Rep, also interacts with the replicative helicase DnaB. We demonstrate that Rep is the only putative accessory helicase whose absence results in an increased chromosome duplication time. We show also that the interaction between Rep and DnaB is required for Rep to maintain rapid genome duplication. Furthermore, this Rep-DnaB interaction is critical in minimizing the need for both recombinational processing of blocked replication forks and replisome reassembly, indicating that colocalization of Rep and DnaB minimizes stalling and subsequent inactivation of replication forks. These data indicate that E. coli contains only one helicase that acts as an accessory motor at the fork in wild-type cells, that such an activity is critical for the maintenance of rapid genome duplication and that colocalization with the replisome is crucial for this function. Given that the only other characterized accessory motor, Saccharomyces cerevisiae Rrm3p, associates physically with the replisome, our demonstration of the functional importance of such an association indicates that colocalization may be a conserved feature of accessory replicative motors.

Lichen sclerosus and immunobullous disease.

We report 3 patients with long-standing lichen sclerosus who subsequently developed new onset erosive disease in affected sites. Repeated biopsies were performed which, although not diagnostic, showed some features of bullous pemphigoid for 1 patient and nonspecific findings for the 2 others. Direct immunofluorescence showed the characteristic findings of bullous pemphigoid in the first and pemphigus vulgaris in the others. All 3 patients were treated with immunosuppressive agents, and their condition improved dramatically.

Rapid resolution of primary vulval adult Langerhans cell histiocytosis with very potent topical corticosteroids.

Langerhans cell histiocytosis is a rare idiopathic disorder with protean clinical presentations. Primary unifocal single-system disease of the vulva is even less common. We report a 62-year-old female patient presenting with an 18-month history of pruritus and burning of the vulva. Clinical examination of the vulva showed a tender nodule of the right labium minus. Histology confirmed Langerhans cell histiocytosis. Systemic involvement was excluded. Within 1 month the use of clobetasol propionate ointment led to resolution of both the patient's symptoms and the clinical appearance of the affected right labium minus. This resolution was maintained 12 months later.

Superficial granulomatous pyoderma of the vulva in a patient receiving maintenance rituximab (MabThera) for lymphoma.

BACKGROUND: Vulval ulceration can be caused by a wide variety of etiological factors including bacterial and viral infections, granulomatous disorders, and malignancy. Superficial granulomatous pyoderma (SGP) is a variant of pyoderma gangrenosum. It is characterized by localized ulcerative lesions that may be precipitated by surgery. We report a case of vulval SPG in an immunocompromised patient. CASE: A 51-year-old woman presented with a 6-week history of severe vulval pain, bleeding, and rapidly progressing ulceration. She had a previous history of relapsed follicular non-Hodgkin lymphoma and was currently receiving regular MabThera (Welwyn Garden City, Hertfordshire, UK). Examination revealed deep ulceration involving the entire vulva and extending into the vagina with areas of necrosis. Histological examination showed ulceration with sparse granulomas and eosinophils. The clinical and histological findings confirmed a diagnosis of SGP. CONCLUSIONS: Vulval ulceration in an immunocompromised patient has a broad differential diagnosis. The possibility of a granulomatous condition such as SGP must always be considered.

Quality of life in the vulvar clinic: a pilot study.

OBJECTIVE: This pilot study aimed to investigate baseline quality of life, anxiety, and depression scores in women attending a multidisciplinary vulvar clinic and to assess whether attendance was associated with improvement in quality of life and psychological symptoms. MATERIALS AND METHODS: Two well-validated questionnaires, namely, the Dermatology Life Quality Index (DLQI) and the Hospital Anxiety and Depression Score (HADS), were completed by women attending a vulvar clinic at their first and a subsequent review visit. Twenty-three women aged between 19 and 77 years completed the study, and their scores were calculated and compared. RESULTS: At the initial visit, 15 (65%) of 23 women scored 6 or higher on the DLQI, indicating that their vulvar disease affected their quality of life to a moderate, very large, or extremely large degree. On review, 12 (52%) of 23 women scored 6 or higher, showing a significant improvement in DLQI between visits (p <.005). The HADS-A (anxiety) score at the initial visit was 8 or higher in 12 (52%) of 23 women, suggesting clinically significant psychological distress. The anxiety score did not statistically change at the review visit. HADS-D (depression) score was initially 8 or higher in 6 (26%) of 23 women but, similar to the anxiety scores, was not statistically different at review. CONCLUSIONS: Most women attending the vulvar clinic have a reduced quality of life. Attending a dedicated multidisciplinary clinic is associated with an improvement in quality of life, but anxiety and depression scores are unchanged. This study is limited by small numbers, and further larger studies are required.

Replication fork blockage by transcription factor-DNA complexes in Escherichia coli.

All organisms require mechanisms that resuscitate replication forks when they break down, reflecting the complex intracellular environments within which DNA replication occurs. Here we show that as few as three lac repressor-operator complexes block Escherichia coli replication forks in vitro regardless of the topological state of the DNA. Blockage with tandem repressor-operator complexes was also observed in vivo, demonstrating that replisomes have a limited ability to translocate through high affinity protein-DNA complexes. However, cells could tolerate tandem repressor-bound operators within the chromosome that were sufficient to block all forks in vitro. This discrepancy between in vitro and in vivo observations was at least partly explained by the ability of RecA, RecBCD and RecG to abrogate the effects of repressor-operator complexes on cell viability. However, neither RuvABC nor RecF were needed for normal cell growth in the face of such complexes. Holliday junction resolution by RuvABC and facilitated loading of RecA by RecF were not therefore critical for tolerance of protein-DNA blocks. We conclude that there is a trade-off between efficient genome duplication and other aspects of DNA metabolism such as transcriptional control, and that recombination enzymes, either directly or indirectly, provide the means to tolerate such conflicts.

Cutaneous manifestations of internal malignancy: diagnosis and management.

An association between systemic malignancy and cutaneous manifestations has long been recognized. The cutaneous features that can occur are numerous and heterogeneous, and many different etiologic mechanisms are represented - from direct tumor invasion of skin or distant metastases to a wide variety of inflammatory dermatoses that may occur as paraneoplastic phenomena. In addition, there are a number of inherited syndromes that carry an increased risk of cutaneous as well as internal malignancies. While some of these inherited syndromes and paraneoplastic phenomena are exceedingly rare, all clinicians will be aware of the common cutaneous manifestations of advanced malignant disease such as generalized xerosis and pruritus. This review classifies these wide-ranging cutaneous manifestations of internal malignancy into five basic groups and provides practical advice regarding diagnosis and screening of patients who initially present with a cutaneous complaint. Also included is up-to-date information on two rapidly expanding and exciting areas of research that are likely to have far-reaching clinical implications: (i) clarification of underlying humoral mechanisms, for example, in the malignant carcinoid syndrome; and (ii) identification of an increasing number of specific genetic defects that confer a susceptibility to malignancy.Increased clinician awareness regarding the associations between these lesions and internal malignancy or inherited syndromes will facilitate screening and early diagnosis.

Neonatal giant congenital nevi with proliferative nodules: a clinicopathologic study and literature review of neonatal melanoma.

BACKGROUND: Review of the literature reveals that congenital malignant melanoma is an exceptionally rare occurrence and has a generally poor prognosis when it does occur. However, benign proliferative melanocytic lesions are known to occur within giant congenital nevi (GCN). This entity is not well recognized and can be confused clinically and histologically with malignant change. OBSERVATIONS: We report 2 cases of GCN in neonates demonstrating benign proliferating nodules present at birth. An initial diagnosis of malignant melanoma was assumed in both cases. Careful histologic analysis, however, revealed these lesions to be benign, as did long-term follow-up of 3.5 years, with both patients remaining well with no evidence of melanoma. Review of the literature suggests that there are 2 clinical patterns of these benign nodules arising within GCNs: small (<1 cm) and large (>1 cm) dermal nodules with varying histologic patterns that we have attempted to categorize. CONCLUSIONS: Our cases illustrate the difficulty in accurate diagnosis of melanocytic lesions in the neonate. We recommend caution in making a diagnosis of malignant melanoma and highlight the possibility that benign lesions can be mistaken for melanoma in this age group. We encourage the acquisition of fixed histologic specimens for accurate diagnosis of melanocytic lesions.

Orofacial reaction to methacrylates in dental materials: a clinical report.

This clinical report presents an unusual response of acute gingivostomatitis caused by contact sensitivity to the methacrylate compounds present in a dental restorative material.