Virtual Cancer Care Beyond the COVID-19 Pandemic: Patient and Staff Perspectives and Recommendations.

PURPOSE: COVID-19 catalyzed rapid implementation of virtual cancer care (VC); however, work is needed to inform long-term adoption. We evaluated patient and staff experiences with VC at a large urban, tertiary cancer center to inform recommendations for postpandemic sustainment. METHODS: All physicians who had provided VC during the pandemic and all patients who had a valid e-mail address on file and at least one visit to the Princess Margaret Cancer Centre in Toronto, Canada, in the preceding year were invited to complete a survey. Interviews and focus groups with patients and staff across the cancer center were analyzed using qualitative descriptive analysis and triangulated with survey findings. RESULTS: Response rates for patients and physicians were 15% (2,343 of 15,169) and 41% (100 of 246), respectively. A greater proportion of patients than physicians were satisfied with VC (80.1 v 53.4%; P < .01). In addition, fewer patients than physicians felt that virtual visits were worse than those conducted in person (28.0 v 43.4%; P < .01) and that telephone and video visits negatively affected the human interaction that they valued (59.8% v 82.0%; P < .01). Major barriers to VC for patients were respect for care preferences and personal boundaries, accessibility, and equitable access. For staff, major barriers included a lack of role clarity, dedicated resources (space and technology), integration of nursing and allied health, support (administrative, clinical, and technical), and guidance on appropriateness of use. CONCLUSION: Patient and staff perceptions and barriers to virtual care are different. Moving forward, we need to pay attention to both staff and patient experiences with virtual care since this will have major implications for long-term adoption into clinical practice.

Schwann cell-matrix coated PCL-MWCNT multifunctional nanofibrous scaffolds for neural regeneration.

Nerve tissue engineering aims to create scaffolds that promote nerve regeneration in the damaged peripheral nervous system. However, there remain some challenges in the construction of scaffolds in terms of mechanical properties and cellular behaviour. The present work aims to develop multifunctional implantable nanofibrous scaffolds for nerve regeneration. Using electrospinning, nanofibrous neat polycaprolactone (PCL) and PCL/multiwalled carbon nanotubes (PCL-MWCNT) composite scaffolds were prepared in random and aligned morphology. Schwann cells and their secreted biochemical factors are responsible for neuronal survival in the peripheral nervous system. Therefore, the acellular matrix of Schwann cells was spin-coated on the PCL-MWCNT scaffolds to aid nerve regeneration. Physicochemical and mechanical properties, and the in vitro cellular response of the developed nanofibrous were investigated. We observed no significant change in fibre diameter between neat PCL and PCL-MWCNT scaffolds regardless of the morphology. However, the inclusion of MWCNT reduced the mechanical strength of nanocomposite scaffolds compared to neat PCL. In vitro study revealed biocompatibility of the developed scaffolds both with and without an acellular matrix. Gene expression study revealed a significant increase in peripheral myelin protein (PMP22) expression on acellular matrix-coated PCL-MWCNT scaffolds compared to neat PCL counterparts. Overall, the results suggested Schwann cell matrix-coated PCL-MWCNT nanofibers as a promising conduit for peripheral nerve regeneration.

Influence of Nanomaterials and Other Factors on Biohydrogen Production Rates in Microbial Electrolysis Cells-A Review.

Microbial Electrolysis Cells (MECs) are one of the bioreactors that have been used to produce bio-hydrogen by biological methods. The objective of this comprehensive review is to study the effects of MEC configuration (single-chamber and double-chamber), electrode materials (anode and cathode), substrates (sodium acetate, glucose, glycerol, domestic wastewater and industrial wastewater), pH, temperature, applied voltage and nanomaterials at maximum bio-hydrogen production rates (Bio-HPR). The obtained results were summarized based on the use of nanomaterials as electrodes, substrates, pH, temperature, applied voltage, Bio-HPR, columbic efficiency (CE) and cathode bio-hydrogen recovery (C Bio-HR). At the end of this review, future challenges for improving bio-hydrogen production in the MEC are also discussed.

Impact of HPV mRNA types 16, 18, 45 detection on the risk of CIN3+ in young women with normal cervical cytology.

BACKGROUND: Despite a well-established cervical cancer (CC) screening program in Norway, the incidence of CC in young women is increasing, peaking at 35 years of age. 25 percent of all women diagnosed with CC had normal cytology within 3 years prior to cancer diagnosis, addressing the need to improve the screening programme to further reduce cancer incidences missed by cytology. OBJECTIVE: We wanted to investigate the detection rate of CIN3+ in women 25-39 years with normal cytology by using a 3-type HPV mRNA test as a targeted quality assurance measure. The control group is women with normal cytology. METHODS: During 2014-2017, samples from 13,021 women 25-39 years of age attending cervical cancer screening were analysed at Nordlandssykehuset, Bodø, Norway, including 1,896 women with normal cytology and HPV mRNA test (intervention group), and 11,125 women with cytology only (control group). The HPV mRNA testing was performed using a 3-type HPV E6/E7 mRNA test (PreTect SEE; direct genotyping 16, 18 and 45). The women were followed-up according to national guidelines throughout December 2021. RESULTS: Of the 13,021 women, 429 women (3.3%) had CIN3+ confirmed by biopsy in the follow-up, including 13 cases of invasive cervical cancer. Of the 1,896 women with normal cytology and HPV mRNA test (intervention group), 49 women (2.6%) had a positive test. The risks of CIN3+ among women with either a positive or negative HPV mRNA test were 28.6% (14/49) and 0.8% (14/1847). None of the women in the intervention group developed cervical cancer during follow-up. Of the 11,125 women with cytology only (control group), 712 women (6.4%) had abnormal cytology (ASC-US+). The risks of CIN3+ among women with abnormal and normal cytology were 17.7% (126/712) and 2.6% (275/10,413). CONCLUSION: By testing women 25-39 years of age with a normal cytology result using a specific 3-type HPV mRNA test, an increase in screening programme sensitivity can be achieved without an excessive additional workload. Women with normal cytology and a negative HPV mRNA test have a very low risk of cervical cancer.

Determination of the Accuracy of Salivary Biomarkers for Periodontal Diagnosis.

BACKGROUND: We aimed to investigate the accuracy of salivary matrix metalloproteinases (MMP)-8 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 in diagnosing periodontitis and in distinguishing periodontitis stages (S)1 to S3. METHODS: This study was a case-control study that included patients with periodontitis S1 to S3 and subjects with healthy periodontia (controls). Saliva was collected, and then, clinical parameters were recorded, including plaque index, bleeding on probing, probing pocket depth, and clinical attachment level. Diagnosis was confirmed by assessing the alveolar bone level using radiography. Salivary biomarkers were assayed using an enzyme-linked immunosorbent assay. RESULTS: A total of 45 patients (15 for each stage) and 18 healthy subjects as controls were included. The levels of all salivary biomarkers and clinical parameters were significantly higher in periodontitis subjects than in the controls. The ROC curve showed that MMP-8, MMP-9, TIMP-1, MMP-8/TIMP-1, and MMP-9/TIMP-1 had statistically significant diagnostic accuracy, with areas under the curve (AUCs) of 0.892, 0.844, 0.920, 0.986, and 1.000, respectively, when distinguishing periodontitis from the controls. Similarly, these biomarkers showed significant diagnostic accuracy in the differentiation of S1 periodontitis from the controls (AUC range from 0.902 to 1.000). CONCLUSIONS: This study suggested that salivary biomarkers exhibited high diagnostic accuracy in distinguishing periodontal health from periodontitis in general as well as S1 periodontitis. Furthermore, TIMP-1 could differentiate S1 from S3.

Adverse events of opioids for cancer-related pain in a resource-limited setting: a cross-sectional study from Sudan.

Aim: Data on the adverse events of opioids for cancer-related pain in Sudanese patients are limited. We conducted this study to evaluate the pattern and severity of adverse events of immediate release morphine, and tramadol used in the treatment of cancer-related pain. A secondary aim was to determine the response rate to opioids for pain control in cancer patients treated at the National Cancer Institute-University of Gezira (NCI-UG), Sudan. Methods: This descriptive cross-sectional study was conducted at NCI-UG between 12 March 2019 and 12 May 2019. A pre-designed questionnaire was used to collect the clinical data of cancer patients on oral opioids for pain control during the study periods. Chi square test was applied to determine whether there is a significant association between the adverse events and the demographic/clinical variables. p value < 0.05 was considered statistically significant in all analyses. Results: One-hundred and thirteen patients were screened in the study. Of these, three suffered from cognitive dysfunction and ten patients declined to participate in the study. Thus, 100 patients met the criteria for inclusion in this study. Breast cancer was the most frequent diagnosis (17%) followed by colorectal cancer (16%). The majority (91%) of patients had advanced or metastatic disease. The most frequently reported opioids-related adverse events were dry mouth (68%), constipation (61%), sedation (49%), nausea (31%) and vomiting (24%). Most of these symptoms were graded as mild to moderate and no patient had grade IV or V adverse events. Constipation and dry mouth were more frequent among patients received morphine compared to patients received tramadol (p value < 0.005). Pain was controlled in 36% of patients, improved in 53% and not controlled in 11% of them. Conclusion: This study shows a high prevalence of opioids-related adverse events. The majority of the opioids-related adverse events were grade I or grade II. There seem to be differences in the prevalence of opioids-related adverse events between patients receiving tramadol and those treated with morphine. Moreover, suboptimal pain control adds to the burden on already limited health resources. Therefore, the adequacy of cancer pain management in our setting should be systematically evaluated and effective cancer pain management programmes should be developed.

Use of the job demands-resource model to understand community pharmacists' burnout during the COVID-19 pandemic.

BACKGROUND: Community pharmacists are one of the most accessible healthcare providers during the COVID-19 pandemic. Whilst playing a vital role in medication supply and patient education, exposure to the pandemic demands and prolonged stressors increase their risk of burnout. OBJECTIVES: Using the Job Demands-Resources model, this study aims to understand the factors that led to community pharmacists' burnout and to identify their coping strategies and perceived recommendations on interventions to mitigate burnout during the COVID-19 pandemic. METHODS: A qualitative phenomenological approach was used with focus groups and interviews of community pharmacists in Qatar who were recruited using purposeful, convenience, and snowballing sampling methods. Interviews were conducted between February and April 2021, were audio-recorded and transcribed verbatim. Using thematic analysis methodology, manual inductive and deductive (based on the model) codes from the interviews were used for synthesis of themes. 11 themes emerged from six focus groups, six dyadic interviews and mini focus groups, and four individual interviews with community pharmacists. RESULTS: The contributing factors to community pharmacists' burnout have been identified as practical job demands, and emotional demands including fear of infection. On the other hand, government and workplace-specific resources, personal characteristics such as resiliency and optimism, as well as the implementation of coping strategies, have reduced their stress and burnout. CONCLUSIONS: The use of the Job Demands-Resources model was appropriate to identify the contributing factors to community pharmacists' burnout during the COVID-19 pandemic. Based on these factors, individual, organizational, and national strategies can be implemented to mitigate burnout in community pharmacists during the pandemic and future emergencies.

Hereditary hemorrhagic telangiectasia in a sudanese patient: A case report.

(HHT) is a rare disorder affecting the skin and body's internal organs with a tendency for bleeding. We report a case of Sudanese 42-year-old with family history of HHT presented with recurrent epistaxis and telangiectasias.

Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features.

The PIDDosome is a multiprotein complex, composed by the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 that induces apoptosis in response to DNA damage. In the recent years, biallelic pathogenic variants in CRADD have been associated with a neurodevelopmental disorder (MRT34; MIM 614499) characterized by pachygyria with a predominant anterior gradient, megalencephaly, epilepsy and intellectual disability. More recently, biallelic pathogenic variants in PIDD1 have been described in a few families with apparently nonsydnromic intellectual disability. Here, we aim to delineate the genetic and radio-clinical features of PIDD1-related disorder. Exome sequencing was carried out in six consanguineous families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals as well as reviewing all the data from previously reported cases. We identified five distinct novel homozygous variants (c.2584C>T p.(Arg862Trp), c.1340G>A p.(Trp447*), c.2116_2120del p.(Val706Hisfs*30), c.1564_1565delCA p.(Gln522fs*44), and c.1804_1805del p.(Gly602fs*26) in eleven subjects displaying intellectual disability, behaviorial and psychiatric features, and a typical anterior-predominant pachygyria, remarkably resembling the CRADD-related neuroimaging pattern. In summary, we outlin`e the phenotypic and molecular spectrum of PIDD1 biallelic variants supporting the evidence that the PIDD1/CRADD/caspase-2 signaling is crucial for normal gyration of the developing human neocortex as well as cognition and behavior.

Silica-Based Bioactive Glasses and Their Applications in Hard Tissue Regeneration: A Review.

Regenerative medicine is a field that aims to influence and improvise the processes of tissue repair and restoration and to assist the body to heal and recover. In the field of hard tissue regeneration, bio-inert materials are being predominantly used, and there is a necessity to use bioactive materials that can help in better tissue-implant interactions and facilitate the healing and regeneration process. One such bioactive material that is being focused upon and studied extensively in the past few decades is bioactive glass (BG). The original bioactive glass (45S5) is composed of silicon dioxide, sodium dioxide, calcium oxide, and phosphorus pentoxide and is mainly referred to by its commercial name Bioglass. BG is mainly used for bone tissue regeneration due to its osteoconductivity and osteostimulation properties. The bioactivity of BG, however, is highly dependent on the compositional ratio of certain glass-forming system content. The manipulation of content ratio and the element compositional flexibility of BG-forming network developed other types of bioactive glasses with controllable chemical durability and chemical affinity with bone and bioactivity. This review article mainly discusses the basic information about silica-based bioactive glasses, including their composition, processing, and properties, as well as their medical applications such as in bone regeneration, as bone grafts, and as dental implant coatings.

Antimicrobial Mechanisms and Effectiveness of Graphene and Graphene-Functionalized Biomaterials. A Scope Review.

Bacterial infections represent nowadays the major reason of biomaterials implant failure, however, most of the available implantable materials do not hold antimicrobial properties, thus requiring antibiotic therapy once the infection occurs. The fast raising of antibiotic-resistant pathogens is making this approach as not more effective, leading to the only solution of device removal and causing devastating consequences for patients. Accordingly, there is a large research about alternative strategies based on the employment of materials holding intrinsic antibacterial properties in order to prevent infections. Between these new strategies, new technologies involving the use of carbon-based materials such as carbon nanotubes, fullerene, graphene and diamond-like carbon shown very promising results. In particular, graphene- and graphene-derived materials (GMs) demonstrated a broad range antibacterial activity toward bacteria, fungi and viruses. These antibacterial activities are attributed mainly to the direct physicochemical interaction between GMs and bacteria that cause a deadly deterioration of cellular components, principally proteins, lipids, and nucleic acids. In fact, GMs hold a high affinity to the membrane proteoglycans where they accumulate leading to membrane damages; similarly, after internalization they can interact with bacteria RNA/DNA hydrogen groups interrupting the replicative stage. Moreover, GMs can indirectly determine bacterial death by activating the inflammatory cascade due to active species generation after entering in the physiological environment. On the opposite, despite these bacteria-targeted activities, GMs have been successfully employed as pro-regenerative materials to favor tissue healing for different tissue engineering purposes. Taken into account these GMs biological properties, this review aims at explaining the antibacterial mechanisms underlying graphene as a promising material applicable in biomedical devices.

Fabrication and in-vitro biocompatibility of freeze-dried CTS-nHA and CTS-nBG scaffolds for bone regeneration applications.

The thought of biodegradable organic-inorganic composites composed of natural polymer chitosan and ceramic nanoparticles (hydroxyapatite and bioglass) can be considered as a solution for hard tissue engineering. In this paper, we described a comparative assessment of chitosan-nanohydroxyapatite (CTS-nHA) and chitosan-nano-bioglass (CTS-nBG) scaffolds. The dispersion of nanoscaled hydroxyapatite (nHA) and bioglass (nBG) in chitosan remained satisfactory. The freeze-dried composite based CTS-nHA and CTS-nBG scaffolds shown porous structure. The physiochemical and morphological analysis of all samples has been performed through X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The SEM image confirmed the presence of spherically shaped nHA particles of 4.20 µm and irregularly shaped nBG particles of 6.89 µm. The TEM analysis revealed the existence of 165.52 to 255.17 nm sized nHA particles and 167.35 to 334.69 nm sized nBG particles. TEM analysis also showed the interconnected structure of CTS-nHA and CTS-nBG nanocomposites. After seven days' incubation period, the CTS-nHA and CTS-nBG scaffolds shown good mineralization behavior in simulated body fluid (SBF). The CTS-nHA scaffolds exhibited enhanced compressive strength and elastic modulus compared with the CTS-nBG sample. The cell culture experiment revealed that fabricated scaffolds had good compatibility with fibroblast cells (L929, ATCC) and MG-63 which are able to adhere, proliferate, and migrate through the porous structure. All the obtained results clearly recommend that pre-loaded hydroxyapatite and bioglass nanoparticles can enhance the apatite formation. The scaffolds with chitosan, bioglass, and hydroxyapatite have better biomechanical characteristics and allow cell growth. Therefore, these scaffolds can be perfect candidates for various hard tissue engineering applications such as bone regeneration.

Oral Dysbiosis in Pancreatic Cancer and Liver Cirrhosis: A Review of the Literature.

The human body is naturally colonized by a huge number of different commensal microbial species, in a relatively stable equilibrium. When this microbial community undergoes dysbiosis at any part of the body, it interacts with the innate immune system and results in a poor health status, locally or systemically. Research studies show that bacteria are capable of significantly influencing specific cells of the immune system, resulting in many diseases, including a neoplastic response. Amongst the multiple different types of diseases, pancreatic cancer and liver cirrhosis were significantly considered in this paper, as they are major fatal diseases. Recently, these two diseases were shown to be associated with increased or decreased numbers of certain oral bacterial species. These findings open the way for a broader perception and more specific investigative studies, to better understand the possible future treatment and prevention. This review aims to describe the correlation between oral dysbiosis and both pancreatic cancer and liver cirrhotic diseases, as well as demonstrating the possible diagnostic and treatment modalities, relying on the oral microbiota, itself, as prospective, simple, applicable non-invasive approaches to patients, by focusing on the state of the art. PubMed was electronically searched, using the following key words: "oral microbiota" and "pancreatic cancer" (PC), "liver cirrhosis", "systemic involvement", and "inflammatory mediators". Oral dysbiosis is a common problem related to poor oral or systemic health conditions. Oral pathogens can disseminate to distant body organs via the local, oral blood circulation, or pass through the gastrointestinal tract and enter into the systemic circulation. Once oral pathogens reach an organ, they modify the immune response and stimulate the release of the inflammatory mediators, this results in a disease. Recent studies have reported a correlation between oral dysbiosis and the increased risk of pancreatic and liver diseases and provided evidence of the presence of oral pathogens in diseased organs. The profound impact that microbial communities have on human health, provides a wide domain towards precisely investigating and clearly understanding the mechanism of many diseases, including cancer. Oral microbiota is an essential contributor to health status and imbalance in this community was correlated to oral and systemic diseases. The presence of elevated numbers of certain oral bacteria, particularly P. gingivalis, as well as elevated levels of blood serum antibodies, against this bacterial species, was associated with a higher risk of pancreatic cancer and liver cirrhosis incidence. Attempts are increasingly directed towards investigating the composition of oral microbiome as a simple diagnostic approach in multiple diseases, including pancreatic and liver pathosis. Moreover, treatment efforts are concerned in the recruitment of microbiota, for remedial purposes of the aforementioned and other different diseases. Further investigation is required to confirm and clarify the role of oral microbiota in enhancing pancreatic and liver diseases. Improving the treatment modalities requires an exertion of more effort, especially, concerning the microbiome engineering and oral microbiota transplantation.

The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells.

BACKGROUND: The control of breast cell survival is of critical importance for preventing breast cancer initiation and progression. The activity of many proteins which regulate cell survival is controlled by reversible phosphorylation, so that the relevant kinases and phosphatases play crucial roles in determining cell fate. Several protein kinases act as oncoproteins in breast cancer and changes in their activities contribute to the process of transformation. Through counteracting the activity of oncogenic kinases, the protein phosphatases are also likely to be important players in breast cancer development, but this class of molecules is relatively poorly understood. Here we have investigated the role of the serine/threonine protein phosphatase 4 in the control of cell survival of breast cancer cells. METHODS: The breast cancer cell lines, MCF7 and MDA-MB-231, were transfected with expression vectors encoding the catalytic subunit of protein phosphatase 4 (PP4c) or with PP4c siRNAs. Culture viability, apoptosis, cell migration and cell cycle were assessed. The involvement of phosphoprotein enriched in astrocytes 15kDa (PEA15) in PP4c action was investigated by immunoblotting approaches and by siRNA-mediated silencing of PEA15. RESULTS: In this study we showed that PP4c over-expression inhibited cell proliferation, enhanced spontaneous apoptosis and decreased the migratory and colony forming abilities of breast cancer cells. Moreover, PP4c down-regulation produced complementary effects. PP4c is demonstrated to regulate the phosphorylation of PEA15, and PEA15 itself regulates the apoptosis of breast cancer cells. The inhibitory effects of PP4c on breast cancer cell survival and growth were lost in PEA15 knockdown cells, confirming that PP4c action is mediated, at least in part, through the de-phosphorylation of apoptosis regulator PEA15. CONCLUSION: Our work shows that PP4 regulates breast cancer cell survival and identifies a novel PP4c-PEA15 signalling axis in the control of breast cancer cell survival. The dysfunction of this axis may be important in the development and progression of breast cancer.

Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

BACKGROUND: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. METHODS: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. RESULTS: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. CONCLUSION: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

p53 Codon 72 arginine/proline polymorphism and cancer in Sudan.

The aim of this report is to determine frequencies and associations of p53 codon 72 arg/pro polymorphism with different types of cancer in Sudan. p53 codon72 arg/pro polymorphism distribution and allele frequencies in 264 samples of different types of cancers were investigated using PCR. The results were compared to 235 normal controls. The results indicated significant differences in frequency and genotype association between different types of cancers. Breast carcinoma patients most prominently showed excess of homozygous arg genotype as compared to controls with an Odd ratio (OR) of 19.44, 95 %CI: 6.6-78.3, P < 0.0001. Less prominently cervical cancer showed genotype effect of 2.4 OR, 95 %CI: 1.12-5.33, P = 0.015, while esophageal cancer had an OR of 0.57, 95 %CI: 0.23-1.42, P = 0.1. In Burkitt's lymphoma, however, in contrast the homozygous arg accounted for only 6.9 %, (OR 0.18, 95 %CI: 0.02-0.89, P = 0.018). We concluded that p53 arg/pro polymorphism has different pattern of frequency in different types of cancer among Sudanese patients, indicating perhaps different etiology and biology of these tumours.

Loss of balancing selection in the betaS globin locus.

BACKGROUND: Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations. METHODS: We investigated the association of haemoglobin HbS in protection from clinical episodes of malaria in two populations/villages where malaria is endemic, but mostly presenting in mild clinical forms. Five-hundred and forty-six individuals comprising 65 and 82 families from the Hausa and Massalit villages respectively were genotyped for HbS. Allele and genotype frequencies as well as departure from Hardy-Weinberg Equilibrium were estimated from four-hundred and seventy independent genotypes across different age groups. Age-group frequencies were used to calculate the coefficient-of-fitness and to simulate the expected frequencies in future generations. RESULTS: Genotype frequencies were within Hardy-Weinberg expectations in Hausa and Massalit in the total sample set but not within the different age groups. There was a trend for a decrease of the HbS allele frequency in Hausa and an increase of frequency in Massalit. Although the HbS allele was able to confer significant protection from the clinical episodes of malaria in the two populations, as suggested by the odds ratios, the overall relative fitness of the HbS allele seems to have declined in Hausa. CONCLUSIONS: Such loss of balancing selection could be due to a combined effect of preponderance of non-clinical malaria in Hausa, and the deleterious effect of the homozygous HbS under circumstances of endogamy.

Sentinel lymph nodes and breast carcinoma: analysis of 70 cases by frozen section.

BACKGROUND: The sentinal node biopsy (SNB) is a reliable method for determining the status of the regional lymph nodes in patients with breast cancer. SNB technology is evolving rapidly, but no standardization has yet been accomplished. The aim of this study is to discuss the accuracy of this procedure and the optimal method for identifying micrometastases. METHODS: We collected data from 70 women with primary invasive breast carcinoma who underwent SNB for breast cancer. We examined two frozen sections levels from each half of each lymph node, as well as a cytology imprint before arriving at the frozen section diagnosis. Immunohistochemistry with pancytokeratin (AE1/AE3) was done on the paraffin sections. For the association between the lymph node size and the possibility of metastases, Student's t test was used and a P value of less than 0.05 was regarded as significant. RESULTS: The number of patients with metastases in SNB was 19, from which 15 cases were correctly diagnosed in frozen sections/imprints and four cases were false negative. The axillary toilet from all cases with SNB metastases smaller than 2 mm showed no additional positive nodes. Lymph node diameter showed a significant association with sentinel node status (P<0.0001). CONCLUSION: Frozen section examination of SNB from patients with breast carcinoma is both specific (100%) and sensitive (79%). Diagnosis of lobular carcinoma can be difficult, and may require immunohistochemistry with cytokeratin for diagnosis. Small metastases in a non-optimal frozen section may be difficult to discern. Cytology imprints add nothing to the diagnosis.