Evaluation of patient dose during a digital breast tomosynthesis.

INTRODUCTION: When the patient dose in mammography is assessed, it is important to evaluate both average glandular dose (AGD) and entrance surface dose (ESD). A dose survey on both AGD and ESD in mammography has never been studied in Sri Lanka. Therefore, the present study aimed to evaluate the patient dose received during a full-field digital breast tomosynthesis (DBT) examination by determining both AGD and ESD. METHODS: The study was performed on 140 patients who underwent DBT examination. The AGD, ESD, compression breast thickness (CBT), half-value layer (HVL), target/filter combination, kVp, and mAs values were obtained from the machine, and AGD for each projection was calculated using the equation proposed by the Dance 2011. RESULTS: The measured mean AGDs and ESDs of both the breasts were statistically significantly lower than the reference values given by European protocol (p < 0.05). There were no statistically significant differences in both AGDs and ESDs between the right and left breast, between right craniocauidal (RCC) and left craniocaudal (LCC), and between right mediolateral oblique (RMLO) and left mediolateral oblique (LMLO) examinations (p > 0.05). The measured median AGDs and ESDs received for MLO projections of both breasts were statistically significantly higher than that of CC projections (p < 0.05). CONCLUSION: The patients receive a low radiation dose during their DBT examination with both lowered AGD and ESD than the recommended values. IMPLICATIONS FOR PRACTICE: The results can be used as a baseline to optimize the radiation dose in mammography in Sri Lanka.

Age and sex related variations of adult human ocular volumes in the Sri Lankan population: an evaluation using magnetic resonance imaging.

INTRODUCTION: Variations in the human ocular volumes are related to ocular pathologies including congenital glaucoma, microphthalmus, buphthalmus, and macrophthalmus. As the currently published reference ocular volumes are prone to physiological and racial variations, population specific values may provide more precision in ophthalmological interventions. This study was conducted to assess the age and sex dependent differences in ocular volumes in Sri Lankan individuals using magnetic resonance imaging (MRI). METHODS: The study was undertaken using the brain MRI scans from 200 patients which were reported as normal. Study sample consisted of patients between 18 years and 90 years of age with 91 male subjects and 109 female subjects. Two independent observers measured ocular volumes using a software-based method and an MRI planimetry based method. Age and sex of the study participants were recorded for the further analysis. RESULTS: Statistically significant differences in both ocular volumes were found between males and females (p < 0.05) when using both volume analysis methods. The mean ± SD ocular volumes obtained as right software based volume, right MRI planimetry volume, left software based volume and left MRI planimetry volume were 6.8 ± 0.6, 6.0 ± 0.6, 6.6 ± 0.7 and 5.9 ± 0.6 cm3 in females and 6.9 ± 0.8, 6.3 ± 0.7, 6.9 ± 0.8 and 6.2 ± 0.7 cm3 in males. While software-based measurements show a significant linear correlation with age in both eyeball volumes, MRI planimetry measurement showed a significant linear correlation with age only in the left eyeball (p < 0.05). Weak negative correlations were found with age in right ocular volume in both MRI planimetry based (r = -0.121) and software based (r = -0.168) measurements and in left ocular volume in MRI planimetry based (r = -0.151) and software based (r = -0.179) measurements. Furthermore, ocular volumes obtained from the software-based method were significantly greater than the MRI planimetry based ocular volumes (p < 0.05) in both eyes, despite having a strong positive correlation. CONCLUSION: The mean ocular volumes obtained from this study revealed a significant variation between the right and left eyes as well as a sexual dimorphism. Moreover, since the two measurement methods show a significant difference, the choice of measurement method should depend on the required accuracy of the eye volume decided with respect to the clinical implication. IMPLICATIONS FOR PRACTICE: Since there are no reference values for Sri Lankan adult ocular volumes, this study may serve that purpose in the current population, while supporting ophthalmologists and radiologists to quantitatively evaluate ocular pathologies and to follow precise interventions.

Reactogenicity to ChAdOx1 nCoV-19 vaccine in health care workers: A multicenter observational study in Sri Lanka.

Introduction: The acceptability of a vaccine is an important factor during mass vaccination programs and this is largely dependent on the symptoms of local and systemic reactogenicity. There is paucity of data on the systemic and local reactions experienced by COVD-19 vaccine recipients in South Asia. Objectives: To identify the early local and systemic reactogenicity of ChAdOx1 nCoV-19 vaccine. Method: A multicenter observational study was performed to identify the reactogenicity to ChAdOx1 nCoV-19 vaccine in healthcare workers following the first dose. Results: There were 4478 participants with a median age of 42 years (IQR 34-51) and 2863 (63.9%) were females. At least one symptom of reactogenicity was reported by 4151 (92.7%). Local reactions were reported by 2612 (58.3%). Systemic reactions were bodyache (3244,72.4%), fatigue (2379, 53.1%), headache (2277, 50.8%), fever (2290, 51.1%), feverishness (1912, 42.7%) and chills (2295, 51.3%). Lower age (p<0.0001) and female gender (p 0.002) were associated with a higher frequency of developing systemic reactions. There was no association between reactogenicity and comorbidities. There were 342 (7.6%) reports of palpitations and one case of ventricular bigeminy. There was one report of anaphylaxis and hospital admissions were reported by 24 (0.5%). One vaccine recipient was managed for possible aseptic meningitis. Conclusion: This study demonstrates that early systemic and local reactions are common. Systemic reactions were more frequent in females and in the younger population. Most symptoms were self- limiting and did not require medical attention or hospital admission. ChAdOx1 nCoV-19 vaccine appears safe in the studied population.

A study on sexual violence inflicted on individuals with intellectual developmental disorder.

BACKGROUND: Rates of violence and abuse perpetrated on people with intellectual and developmental disability (IDD) have been reported to be significantly higher than on individuals without disability. However, rates of sexual violence against people with IDD in some less industrialized countries, such as Sri Lanka, have not been previously reported. OBJECTIVES: To describe characteristics of victims and perpetrators as well as the types of abuse found during medicolegal examinations of patients with IDD. METHODOLOGY: This is a cross-sectional study that utilized a convenience sample of individuals with IDD who presented after abuse at three hospitals in Sri Lanka from 2011 to 2015. RESULTS: All subjects had mild or moderate IDD; 90.2% were females; 48.8% were between the ages of 11-20 years; and 47.56% lived with both parents. Most of the victims (48%) disclosed the abuse and 29% of the events were witnessed. The perpetrators were known to the victim 49% of the time, and 49% reported a single episode of abuse. Victims reported that the abuse had taken place in the victim's house 47% of the time. Vaginal intercourse and intercrural intercourse were the most common types of abuse, and 23% of patients were found to be pregnant. CONCLUSION: In this study that relied on victim report and medicolegal investigation, parties close to the victim usually perpetrated the sexual abuse. Therefore, it is important to have more than one level of support and care for individuals with IDD so there is more opportunity for reporting.

Rickettsioses in the central hills of Sri Lanka: serological evidence of increasing burden of spotted fever group.

OBJECTIVES: To study the epidemiology, clinical features, and changing pattern of rickettsial infections on the western slopes of the hilly Central Province of Sri Lanka over 6 years. METHODS: All patients with rickettsial infections who presented to the Teaching Hospital, Peradeniya were studied prospectively from January 2002 to December 2007. An immunofluorescent antibody assay (IFA) was used to confirm the diagnosis. RESULTS: Of the 371 clinical cases of rickettsial infection, 122 underwent IFA to confirm the diagnosis. Species-specific IgG antibodies were positive in 105/122 (86.1%) cases: 43/105 (40.9%) to Rickettsia conorii and 6/105 (5.7%) to Orientia tsutsugamushi, with mixed antibody reactivity to more than one antigen in 56/105 (53.3%) cases, including Rickettsia typhi in 27/105 (25.7%). Among those with mixed IgG reactivity, IgM assays were used to detect pathogens responsible for acute infections. Finally, a total of 55 spotted fever group (SFG) infections, seven scrub typhus infections, and one case of murine typhus were identified. Of the 105 positive cases, 53 (50.5%) were male and 52 (49.5%) were female, and the mean age was 40 years (range 11-83 years). In the SFG patients, 13/55 (24%) had severe vasculitis with fern leaf type skin necrosis and 17/55 (31%) had arthritis. Three patients (5%) had an altered level of consciousness. A patient with scrub typhus had transient deafness. None of the 105 patients had an eschar. CONCLUSIONS: It appears that SFG rickettsioses are on the rise in the hilly Central Province of Sri Lanka, whilst murine typhus and scrub typhus are present at a lower rate.

Inadequacy of the risk factor based approach to detect gestational diabetes mellitus.

OBJECTIVE: To evaluate the present risk factor based approach in diagnosis of gestational diabetes mellitus (GDM) in Sri Lanka in comparison with new guidelines proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). METHODS: A community based cross sectional descriptive study was conducted among pregnant women with gestational age of 24-28 weeks and residing in Anuradhapura district. All eligible pregnant women from selected Medical Officers of Health areas were invited to participate. The 75 g oral glucose tolerance test was carried out among all participants. RESULTS: According to IADPSG criteria, 36 (8.9%) of pregnant women had GDM, compared to 29 (7.2%) according to WHO criteria. Prevalence of GDM in the study population (positive by one or both methods) was 10.6% (n=43) (95% CI 7.9-13.9%). Of these 43 women,22 (51.1%) had positive results by both methods. Seven (16.3%) and 14 (32.6%) mothers were positive only according to WHO and IADPSG criteria respectively. Out of 29 mothers who fulfilled WHO criteria, only one had an abnormal fasting plasma glucose, but 28 had abnormal 2 hour values. A total of 170 (42.0%) participants had at least one risk factor or early indicator of GDM. A risk based approach would have detected only 22 GDM patients according to IADPSG criteria, missing 14 cases (38.9%) who did not have any of the risk factors for GDM. CONCLUSIONS: The risk factor based approach misses more than one third of GDM cases. Urgent revision of current GDM screening guidelines is recommended.

A review of telemedicine interventions in diabetes care.

We reviewed the literature concerning the use of telemedicine interventions in diabetes care. The PubMed database was searched for randomized controlled trials concerning the use of telemedicine for patients with type 1 or type 2 diabetes. A total of 27 articles (studies) met the inclusion criteria. The interventions concerned videoconferencing (n = 8), mobile phones (n = 10) and telephone calls (n = 9). There was metabolic improvement in 23 studies, which was significant in 12 out of 23 (44%). Only two studies (8%) reported a negative clinical outcome. The majority of the studies (n = 19; 70%) employed behavioural therapy as the key intervention. The medium used for interaction in behavioural therapy intervention was videoconferencing (n = 7), mobile phone (n = 4), telephone calls (n = 8), feedback letters (n = 2). Telemedicine appears to be a promising alternative to conventional therapy.

High efficacy of bolus methylprednisolone in severe leptospirosis: a descriptive study in Sri Lanka.

BACKGROUND: In 2008, an outbreak of leptospirosis caused high mortality in Sri Lanka. The General Hospital, Peradeniya recorded nine deaths in May, which prompted the medical staff to change the treatment protocol. Addition of intravenous methylprednisolone (MP) to the treatment regimen of severely ill patients was implemented on the basis of immune mediated pathogenesis of the disease to reduce mortality. METHODS: The day MP commenced (25 May 2008), the study period was divided into a 'pre-MP period' and an 'MP period'. A clinical score ranging from 0-6 was applied to assess the severity of the infection. A score ≥2 was considered severe. Thus, 62 patients received bolus MP 500 mg intravenously for 3 days, followed by oral 8 mg for 5 days (MP given). Ten patients to whom MP was withheld were included in the MP period severe group (n=72). The same score was applied to pre-MP periods and 60 cases were identified as the historical control group (pre-MP period severe). RESULTS: There were 78 and 149 cases of leptospirosis in the pre-MP period and MP period, respectively. Of these cases, 17 and 16 patients died, with case death rates of 21.8% and 10.7%, respectively; the difference was significant (p=0.025). The survival rate at score 4 in the MP period severe group was 100% (16 of 16), compared to 38% (5 of 13) in pre-MP period severe group; this difference was highly significant (p<0.001). Six patients who died despite MP therapy had a clinical score of 5 or 6; four were alcohol consumers, and two had heart disease and hypertension. CONCLUSION: MP may reduce mortality in patients with severe leptospirosis, except in cases with established multiple organ dysfunction and comorbidities. Therefore, early administration of MP seems advisable.

Interaction of the cyanobacterial toxin cylindrospermopsin with the eukaryotic protein synthesis system.

The cyanobacterial toxin cylindrospermospin (CYN) was shown to inhibit the eukaryotic protein synthesis apparatus with similar potency in plant and mammalian cell extracts, IC(50) of 334 nM in wheat germ extract and 110 nM in reticulocyte lysate. [(14)C] CYN binding was assessed in reticulocyte lysates, following separation of ribosomes from free toxin on Sephadex G-50 size exclusion columns. While toxin binding was shown to be concentration-dependent (60-600 nM [(14)C] CYN), it did not correlate with ribosome content. The molar ratio of toxin to ribosomes was 0.02:1 at the binding plateau. Significant binding of [(14)C] CYN was identified in both the ribosome fraction (> 90% total ribosomes) and the first wash fraction eluting from the Sephadex G-50 column, despite the low ribosome content (<10% total ribosomes) in the latter. Bound [(14)C] CYN could be partially displaced by incubation with an excess of unlabelled CYN in both the ribosome and wash fractions, indicating a non-covalent linkage. Molecular weight cut-off filters identified that [(14)C] CYN was associated with high molecular weight material > 100 kDa. These results suggest that CYN's target may not be the ribosome itself, but rather one of the soluble proteins associated with the eukaryotic translation system.

Are tsunami survivors satisfied with the provision and quality of healthcare they received?

The objective of this study is to evaluate the perceptions of Internally Displaced Persons (IDPs) in tsunami relief camps on provision and quality of health care services, during the aftermath of the disaster. A randomly selected health administrative area in the Southern Province of Sri Lanka is selected. Two approaches using both quantitative and qualitative methods. The study assessed the perceptions of IDPs regarding on provision and quality of health care facilities, using an interviewer administered questionnaire (survey) in 200 family units. In-depth interviews were conducted with IDPs and relevant health authorities. A majority (88%) of the people was satisfied with the immediate medical assistance. However 48% of IDPs and authorities felt that frequency of visits paid by medical teams have decreased over time. Fifty-three percent were dissatisfied with the toilet facilities provided. A majority was satisfied with health education (82%) and supply of drinking water (80%). Tsunami survivors felt that health services provided during the intermediate phase was unsatisfactory compared to the immediate phase. We recommend attention to ensuring ongoing access to health care and to improving the sanitary facilities in the camps.

Chlorination for degrading saxitoxins (paralytic shellfish poisons) in water.

Chlorination was investigated as a treatment option for degrading and thus removing saxitoxins (paralytic shellfish poisons, PSPs) produced by cyanobacteria (blue-green algae) from water. It was found to be effective with the order of ease of degradation of the saxitoxins being GTX5 (B1) approximately dcSTX > STX > GTX3 approximately C2 > C1 > GTX2. However the effectiveness of chlorine was pH dependent. Degradation as a function of pH was not linear with the degree of degradation increasing rapidly at around pH 7.5. At pH 9 > 90% removal was possible provided a residual of 0.5 mg l(-1) free chlorine was present after 30 min contact time. The more effective degradation at higher pH was unexpected as chlorine is known to be a weaker oxidant under these conditions. The more effective degradation, then, must be due to the toxins, which are ionisable molecules, being present in a form at higher pH which is more susceptible to oxidation. The feasibility of using chlorine to remove saxitoxins during water treatment will therefore depend strongly on the pH of the water being chlorinated. Degradation may be improved by pH adjustment but may not be a practical solution. Although saxitoxins were degraded in that the parent compounds were not detected by chemical analysis, there is no indication as to the nature of the degradation products. However, acute toxicity as determined by the mouse bioassay was eliminated.

Genotoxicity investigation of a cyanobacterial toxin, cylindrospermopsin.

Cylindrospermopsin (CYN), a potent cyanobacterial hepatotoxin produced by Cylindrospermopsis raciborskii and other cyanobacteria, is regularly found in water supplies in many parts of the world, and has been associated with the intoxication of humans and livestock. In this study, Balb/c mice were injected via the intraperitoneal (IP) route with a single dose of 0.2 mg/kg CYN. Animals were sacrificed at 6, 12, 24, 48 and 72 h. DNA was isolated from the mouse livers, and examined for strand breakage by alkaline gel electrophoresis (pH 12). Significant DNA strand breakage was observed in the mouse liver exposed to CYN, suggesting that induction of DNA strand breakage is probably one of the key mechanisms for CYN genotoxicity.

Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease.

High-resolution crystal structures are described for seven macrocycles complexed with HIV-1 protease (HIVPR). The macrocycles possess two amides and an aromatic group within 15-17 membered rings designed to replace N- or C-terminal tripeptides from peptidic inhibitors of HIVPR. Appended to each macrocycle is a transition state isostere and either an acyclic peptide, nonpeptide, or another macrocycle. These cyclic analogues are potent inhibitors of HIVPR, and the crystal structures show them to be structural mimics of acyclic peptides, binding in the active site of HIVPR via the same interactions. Each macrocycle is restrained to adopt a beta-strand conformation which is preorganized for protease binding. An unusual feature of the binding of C-terminal macrocyclic inhibitors is the interaction between a positively charged secondary amine and a catalytic aspartate of HIVPR. A bicyclic inhibitor binds similarly through its secondary amine that lies between its component N-terminal and C-terminal macrocycles. In contrast, the corresponding tertiary amine of the N-terminal macrocycles does not interact with the catalytic aspartates. The amine-aspartate interaction induces a 1.5 A N-terminal translation of the inhibitors in the active site and is accompanied by weakened interactions with a water molecule that bridges the ligand to the enzyme, as well as static disorder in enzyme flap residues. This flexibility may facilitate peptide cleavage and product dissociation during catalysis. Proteases [Aba67,95]HIVPR and [Lys7,Ile33,Aba67,95]HIVPR used in this work were shown to have very similar crystal structures.

The Enterococcus hirae copper chaperone CopZ delivers copper(I) to the CopY repressor.

Expression of the cop operon which effects copper homeostasis in Enterococcus hirae is controlled by the copper responsive repressor CopY. Purified Zn(II)CopY binds to a synthetic cop promoter fragment in vitro. Here we show that the 8 kDa protein CopZ acts as a copper chaperone by specifically delivering copper(I) to Zn(II)CopY and releasing CopY from the DNA. As shown by gel filtration and luminescence spectroscopy, two copper(I) are thereby quantitatively transferred from Cu(I)CopZ to Zn(II)CopY, with displacement of the zinc(II) and transfer of copper from a non-luminescent, exposed, binding site in CopZ to a luminescent, solvent shielded, binding site in CopY.

X-ray absorption spectroscopy of cadmium phytochelatin and model systems.

Higher plants, algae and some yeasts respond to potentially toxic heavy metals such as cadmium by synthesizing phytochelatins and related cysteine-rich polypeptides. We have used X-ray absorption spectroscopy to study the nature of cadmium binding in such peptides isolated from maize (Zea mays) exposed to low levels of cadmium, and in two synthetic cadmium-peptide complexes, Cd-(gamma-Glu-Cys)3Gly and Cd-(alpha-Glu-Cys)3Gly. We have used the synthetic ions [Cd(SPh)4]2-, [Cd4(SPh)10]2- and [S4Cd10(SPh)16]4-as crystallographically defined models for the cadmium site. The Cd K-edge extended X-ray absorption fine structure (EXAFS) data, together with the Cd K, LI, LII and LIII near-edge spectra, reveal a predominantly tetrahedral coordination of cadmium by sulfur in both the phytochelatin and synthetic peptide complexes. In particular, the Cd LIII-edge lacks a peak at 3534.9 e V which was found to be prominent for oxygen- or nitrogen-coordinated species. The Cd-S distance in the phytochelatin complex is 2.54 A. The Cd K-edge EXAFS does not show any isolated, well-defined Cd-Cd interactions; however, contrary to the conclusion of previous work, their absence is not necessarily indicative of isolated cadmium-thiolate ligation. Evidence from other studies suggests that high static disorder, combined with a large vibrational component, serve to effectively wash out this contribution to the EXAFS. The sulfur K-edge, moreover, shows a low-energy feature both in the phytochelatin and in the synthetic cadmium-peptide complexes which is consistent with sulfide bound in a cluster with cadmium as found for [S4Cd10(SPh)16]4-. This feature strongly suggests the presence of a polynuclear cadmium cluster in maize phytochelatin.