Brain MRI segmentation of Zika-Exposed normocephalic infants shows smaller amygdala volumes.

BACKGROUND: Infants with congenital Zika syndrome (CZS) are known to exhibit characteristic brain abnormalities. However, the brain anatomy of Zika virus (ZIKV)-exposed infants, born to ZIKV-positive pregnant mothers, who have normal-appearing head characteristics at birth, has not been evaluated in detail. The aim of this prospective study is, therefore, to compare the cortical and subcortical brain structural volume measures of ZIKV-exposed normocephalic infants to age-matched healthy controls. METHODS AND FINDINGS: We acquired T2-MRI of the whole brain of 18 ZIKV-exposed infants and 8 normal controls on a 3T MRI scanner. The MR images were auto-segmented into eight tissue types and anatomical regions including the white matter, cortical grey matter, deep nuclear grey matter, corticospinal fluid, amygdala, hippocampus, cerebellum, and brainstem. We determined the volumes of these regions and calculated the total intracranial volume (TICV) and head circumference (HC). We compared these measurements between the two groups, controlling for infant age at scan, by first comparing results for all subjects in each group and secondly performing a subgroup analysis for subjects below 8 weeks of postnatal age at scan. ZIKV-exposed infants demonstrated a significant decrease in amygdala volume compared to the control group in both the group and subgroup comparisons (p<0.05, corrected for multiple comparisons using FDR). No significant volume differences were observed in TICV, HC, or any specific brain tissue structures or regions. Study limitations include small sample size, which was due to abrupt cessation of extramural funding as the ZIKV epidemic waned. CONCLUSION: ZIKV-exposed infants exhibited smaller volumes in the amygdala, a brain region primarily involved in emotional and behavioral processing. This brain MRI finding may lead to poorer behavioral outcomes and warrants long-term monitoring of pediatric cases of infants with gestational exposure to Zika virus as well as other neurotropic viruses.

Nutritional intake of sport undergraduates in Sabaragamuwa University of Sri Lanka.

BACKGROUND: Nutritional intake plays an important role in determining energy availability which is vital to health, wellbeing, and sports performance in an active population. This research assessed the sports undergraduates' nutritional intake compared to the Dietary Guidelines for Americans and nutrition goals provided by WHO. METHODS: This study is a quantitative, cross-sectional descriptive study. One hundred and one (n = 101) sports undergraduates aged between 20 to 23 years were recruited and the nutrient intake was assessed using the three-day food diary method and quantified the macro and micronutrients by the food composition database. One sample t-test was performed to compare the mean nutrient intakes with the lowest recommendation values. RESULTS: Though most undergraduates were able to meet the dietary requirements in carbohydrates, they were deficient in their protein intake and exceeded in fats intake. Further, both male and female students were deficient in their daily energy intake (1723 kcal, 1607 kcal) and dietary fiber intake (8 g, 11 g). The saturated fat intake was met by all students while 20% of males and 21% of females exceeded the recommendations (< 10%). The micronutrient intake of vitamins such as C, B1, B2, B9, and B12 and minerals such as Calcium, Magnesium, and Potassium, were significantly below the recommendations (p < 0.05) except for vitamin B3 niacin. CONCLUSIONS: Providing a nutritionally valuable meal is essentially required to maintain both physical and mental fitness. Our results revealed that the Sri Lankan sport science undergraduates do not have an adequate daily dietary intake of energy, proteins, calcium, magnesium, potassium, and vitamins such as C, B1, B2, B9, and B12.

Air Leak Syndrome In Patients With Severe Covid Pneumonia.

Abstract: There are number of emerging studies that link the air leak syndrome (ALS) with COVID 19 disease but still data to explain the association, incidence and outcome in these patients is lacking. We aim to understand the risk factors and clinical outcome of these air leakage events in COVID 19 patients admitted to our institution. Methods: This is a single-centered case series conducted at the COVID unit of the SMBBIT in Karachi, Pakistan. Data collection was done from April 24, 2020 to June 10, 2021. Results: There were 19 patients with severe COVID pneumonia who developed air leaks. Most common finding was subcutaneous emphysema 94%. Four patients (21%) didn't receive positive pressure ventilation in any form. Median time of developing air leak from admission is 5 [2-9] and from PPV is 2 [1-3] days. There was high percentage of mortality 84.5 % in these patients.

Elevated nitric oxide and carbon monoxide concentration in nasal-paranasal sinus air as a diagnostic tool of migraine: a case - control study.

BACKGROUND: A recent study showed that 60-s paranasal air suction results in an immediate pain relief in acute migraine. This is the study to assess the Nitric Oxide (NO) and Carbon Monoxide (CO) concentration in nasal-paranasal sinus air of migraine patients and to compare it with healthy controls. METHODOLOGY: The NO and CO levels of air sucked out from nasal-paranasal sinuses of 20 migraine adolescent and young adults among school students, aged 16 -19 years, and 22 healthy similar aged school students as controls were measured as key responses using a portable NO and a portable CO analyzer. RESULTS: Patients had comparatively high values compared to the controls for paranasal NO (both left and right sides), paranasal CO (both left and right sides), Fraction Exhaled NO (FeNO) and Fraction Exhaled CO (FeCO). Patients had median paranasal NO contents of 132.5 ppb and 154 ppb on left and right sides respectively compared to 36 ppb and 34.5 ppb corresponding values in controls (P <  0.0001). Similar pattern was observed with paranasal CO (P <  0.0001). FeNO and FeCO content were also higher in patients (P <  0.0001). Receiver characteristic operating curves of all gas measurements showed that they all could classify patients and controls effectively and NO was the most effective followed by paranasal CO. After air suction, the mean pain scores of general headache and tenderness dropped by a very large margin in migraine patients (P <  0.0001). CONCLUSIONS: Suctioned out high nasal-paranasal sinus NO and CO levels can be used to distinguish migraine patients from healthy subjects. In fact, suctioned out paranasal NO measurements of both sides with a cutoff point of 50 ppb provided a perfect classification of patients and controls. Increased sinus NO and CO during acute episode of migraine is an observation we had and we agree that further studies are needed to conclude that NO and CO can be a causative molecule for migraine headache. TRAIL REGISTRATION: Clinical Trial Government Identification Number - 1548/2016. Ethical Clearance Granted Institute - Medical Research Institute, Colombo, Sri Lanka (No 38/2016). Sri Lanka Clinical Trial Registration number: SLCTR/ 2017/018 (29/06/2017). Approval Granting Organization to use the device in the clinical trial- National Medicines Regulatory Authority Sri Lanka (16/06/2018), The device won award at Geneva international inventers exhibition in 2016 and President award in 2018 in Sri Lanka. It is a patented device in Sri Lanka and patent number was SLKP/1/18295. All methods were carried out in accordance with CONSORT 2010 guidelines.

Effectiveness of paranasal air suction on acute migraine using portable air sucker - a randomized, double blind study.

BACKGROUND: Migraine is a primary headache disorder and is the most common disabling primary headache disorder that occurs in children and adolescents. A recent study showed that paranasal air suction can provide relief to migraine headache. However, in order to get the maximum benefit out of it, an easy to use effective air sucker should be available. Aiming to fulfil the above requirement, a randomized, double blind control clinical trial was conducted to investigate the efficacy of a recently developed low-pressure portable air sucker. METHODS: Eighty-six Sri Lankan school children of age 16-19 years with migraine were enrolled for the study. They were randomly allocated into two groups, and one group was subjected to six intermittent ten-second paranasal air suctions using the portable air sucker for 120 s. The other group was subjected to placebo air suction (no paranasal air suction). The effect of suction using portable air sucker was the primary objective but side of headache, type of headache, and gender were also studied as source variables. The primary response studied was severity of headache. In addition, left and right supraorbital tenderness, photophobia, phonophobia, numbness over the face and scalp, nausea and generalized tiredness/weakness of the body were studied. The measurements on all those variables were made before and after suction, and the statistical analysis was performed based on before and after differences. As a follow-up, patients were monitored for 24-h period. RESULTS: There was a significant reduction in the severity of headache pain (OR = 25.98, P < 0.0001), which was the primary outcome variable, and other migraine symptoms studied, tenderness (left) (OR = 289.69, P < 0.0001), tenderness (right) (OR > 267.17, P < 0.0001), photophobia (OR = 2115.6, P < 0.0001), phonophobia (OR > 12.62, P < 0.0001) nausea (OR > 515.59, P < 0.0001) and weakness (OR = 549.06, P < 0.0001) except for numbness (OR = 0.747, P = 0.67) in the treatment group compared to the control group 2 min after the suction. These symptoms did not recur within 24-h period and there were no significant side effects recorded during the 24-h observation period. CONCLUSION: This pilot study showed that low-pressure portable air sucker is effective in paranasal air suction, and suction for 120 s using the sucker can provide an immediate relief which can last for more than 24-h period without any side effects. TRAIL REGISTRATION: Clinical Trial Government Identification Number - 1548/2016. Ethical Clearance Granted Institute - Medical Research Institute, Colombo, Sri Lanka (No 38/2016). Sri Lanka Clinical Trial Registration No: SLCTR/2017/018 . Date of registration = 29/ 06/2017. Approval Granting Organization to use the device in the clinical trial- National Medicines Regulatory Authority Sri Lanka (16 Jan 2018), The device won award at Geneva international inventers exhibition in 2016 and President award in 2018 in Sri Lanka. It is a patented device in Sri Lanka and patent number was SLKP/1/18295. All methods were carried out in accordance with CONSORT 2010 guidelines.

Paranasal sinus air suction for immediate pain relief of acute migraine - a randomized, double blind pilot study.

BACKGROUND: Migraine is a primary headache disorder, which cause significant disability in adolescence. This double blind, randomized clinical trial assessed the immediate effects of suction of paranasal sinus air during an acute migraine episode. METHODS: A randomized, double blind study was conducted with 56 selected Sri Lankan school children of 16-19 years of age. Participants who met International Headache Society criteria for migraine (with or without aura) were included in the study. Subjects were randomly allocated into 2 groups where one group was subjected to three intermittent 10 sec paranasal air suctions with a ten sec suction free interval between two suctions for each nostril and the other group was subjected to placebo air suction (no paranasal air suction) in similar arrangement. Severity of headache and sub-orbital tenderness before and after suction were recorded using standard pain rating scale. RESULTS: After dropouts, treated and placebo groups consisted of 27 and 23 subjects respectively. The mean headache pain score drop in the treated group was significantly higher compared to that of the control group. Moreover, there was a difference in the treatment response between the types of headache (with or without aura). With respect to tenderness there was a statistically significant drop in the treated group compared to the control. In general, airflow rates in left and right nostrils were different in these subjects. However such difference was not seen in the tenderness on two sides. Nevertheless it was revealed that airflow rate has a slight negative correlation with the tenderness irrespective of the side. CONCLUSION: Sixty-second paranasal air suction can provide an immediate pain relief for acute migraine in adolescents. We did not assess pain outcomes beyond 60 s, but the initial responses suggests the need to further study the efficacy of paranasal suction in migraine. A further study is suggested to evaluate the acute effects, efficacy and side effects of paranasal air suction using follow up over a prolong period. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry SLCTR/2017/018 , 29 Jun 2017. Retrospectively registered.

Risk of low birth weight on adulthood hypertension - evidence from a tertiary care hospital in a South Asian country, Sri Lanka: a retrospective cohort study.

BACKGROUND: Although low birth weight (LBW) is common in South Asian region there are not many studies being done to evaluate LBW and adulthood hypertension association in this region, including in Sri Lanka. Although this association has been studied in other regions, most studies have not evaluated this association in the presence of socioeconomic and lifestyle factors. This study was conducted to investigate whether low birth weight (LBW) is associated with adulthood hypertension after adjusting for other potential risk factors of hypertension. METHODS: Nearly 15,000 individuals born during 1950 to 1965 were selected and invitations were sent to their original addresses. Out of them 217 individuals responded and among them birth weight was recovered for 122 individuals. Separate linear logistic models were fitted to model high systolic blood pressure (SBP: systolic blood pressure > 140 mmHg), high diastolic blood pressure (DBP: diastolic blood pressure > 90 mmHg) and hypertension (either SBP > 140 mmHg or DBP > 90 mmHg). RESULTS: Separate linear logistic model fitting revealed LBW having a significant association with high SBP (OR = 2.89; 95% CI: 1.01 to 8.25; P = 0.04), and hypertension (OR = 3.15; 95% CI: 1.17 to 9.35; P = 0.03), but not with high DBP (OR = 0.75; 95% CI: 0.22 to 2.16; P = 0.62), when effect of LBW was studied after adjusting for all other potential risk factors. CONCLUSIONS: LBW has a tendency to cause high adult blood pressure in South Asian region, and the findings are consistent with previous work on LBW and adulthood hypertension association in other regions of the world.

The effects of an Ayurvedic medicinal toothpaste on clinical, microbiological and oral hygiene parameters in patients with chronic gingivitis: a double-blind, randomised, placebo-controlled, parallel allocation clinical trial.

INTRODUCTION: Plant derived preparations have been essential components for maintenance of oral hygiene and the treatment of oral diseases globally since ancient times. Acacia chundra Willd, Adhatoda vasica Nees., Mimusops elengi L., Piper nigrum L., Pongamia pinnate L. Pirerre, Quercus infectoria Olivier., Syzygium aromaticum L., Terminalia chebula Retz., Zingiber offici-nale Roscoe., individually or in combination, have been used for this purpose because of their beneficial effects. OBJECTIVES: To study the efficacy of an Ayurvedic toothpaste containing these herbs in patients with chronic gingivitis. METHODS: Otherwise healthy males and non-pregnant females (n=80) aged 18-35 years with ≥20 teeth were randomly assigned to Group 1 (herbal toothpaste) and Group 2 (placebo toothpaste). Quigley Hein plaque index (PS), bleeding on probing (BOP) and probing pocket depth (PPD), were recorded for all teeth at six sites, and one ml of resting saliva was collected to ascertain anaerobic and aerobic bacterial counts at baseline, and at 4, 8, 12 and 24 weeks. Full-mouth prophylaxis was performed and instructions for brushing with the allocated toothpaste for 6 months were given at baseline. Sixty-six participants, 34 in Group 1 and 32 in Group 2 completed the study. Clinical examinations were performed by the same examiner blinded to group allocation. RESULTS: Linear mixed model analysis revealed significant reductions of PS, BOP, PPD (p<0.0001) and total salivary anaerobic counts (p<0.05) in Group 1 at all prescribed visits compared to Group 2. Moreover the reduction increased overtime. No unpleasant effects of toothpaste use were reported. CONCLUSIONS: This study provides robust evidence of the beneficial antiplaque and antigingivitis effects of the test herbal toothpaste Sudantha® on patients with chronic gingivitis.

Variation in post-adenotonsillectomy admission practices in 24 pediatric hospitals.

OBJECTIVES/HYPOTHESIS: There is controversy about which children should be admitted after adenotonsillectomy (T&A) and limited clinical evidence to help with this decision. Current practice has evolved based on empirical or anecdotal evidence. We sought to identify practice variations in postoperative admission after T&A in tertiary care pediatric hospitals. STUDY DESIGN: Retrospective database study using administrative information stored in the Pediatric Health Information System (PHIS) database. METHODS: There were 29,920 T&As performed in 24 pediatric hospitals included in the PHIS database between July 1, 2009 and June 30, 2010. Patients were identified as outpatient (discharged the same day) or inpatient (not discharged on the day of surgery). We examined admission rates across different hospitals stratified by age, obstructive sleep apnea (OSA), and other complex chronic conditions. RESULTS: Younger age, the existence of a complex chronic condition, and OSA were all associated with higher post-T&A admission rates. Admission rates ranged from >94% for children under 2 years of age, with OSA and at least one medical comorbidity, to 14% for children older than 5 years, without OSA and without any medical comorbidities. Between-hospital variability was extreme; for example, for 3 to 5 year olds, the admission rate varied from 5% to 90% between hospitals. Very significant variation remained even after controlling for age, comorbidities, and OSA. CONCLUSIONS: Post T&A admission rates vary tremendously across comparable tertiary-care pediatric hospitals. There is a crucial need for a better understanding of the risk of complications on the first postoperative night, and the appropriate indications for monitored admission on that night. LEVEL OF EVIDENCE: 4.

A systematic review of skin substitutes for foot ulcers.

BACKGROUND: Bioengineered and allograft-derived skin substitutes are increasingly available and marketed for use in the healing of chronic wounds. Plastic surgeons should have evidence-based information available to guide their use of these products. The authors systematically reviewed the literature to determine the published outcomes and effectiveness of different skin substitutes for healing chronic foot ulcers. METHODS: A broad literature search of the MEDLINE, EBSCO, EMBASE, and the Cochrane Central Register of Controlled Trials databases was undertaken. Relevant studies were selected by three independent reviewers to include randomized controlled trials or systematic reviews examining the use of skin substitutes on foot ulcers. Results were narrowed further by the application of predetermined inclusion and exclusion criteria. Studies were assessed for quality and data were extracted regarding study characteristics and objective outcomes. RESULTS: Of an initial 271 search results, 15 randomized controlled trials, one prospective comparative study, and five systematic reviews were included in the systematic review. Most of the included clinical studies were of moderate to low quality by objective standards, and reported results using cell-based skin substitutes. The primary outcome examined, success rate of complete healing, was equivalent to or better than that of standard therapy for all skin substitutes examined. CONCLUSIONS: A convincing body of evidence supports the effectiveness of living cell-based skin substitutes as an adjunctive therapy for increasing the rate of complete healing in chronic foot ulcers when basic tenets of wound care are also being implemented. Acellular skin substitutes also show some promise for treatment of foot wounds but require further study. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Local recurrence of rectal cancer in patients not receiving neoadjuvant therapy - the importance of resection margins.

OBJECTIVES: Local recurrence of rectal cancer reduces quality of life and survival. A multi-factorial linear logistic model was used to analyse risk factors for local recurrence in rectal cancer in patients not receiving preoperative chemo-radiation. METHODS: A case-control study of patients with rectal cancer having surgery with curative intent, between 1996 and 2008. Eighteen putative risk factors for local recurrence were subjected to uni-variate analysis. Significant factors were selected for multi-factorial analysis. RESULTS: Twenty-one patients with local recurrence (cases) and 78 controls were selected. Uni-variate analysis showed significant associations with recurrence for nodal stage (N) (p=0.027), metastasis (M) (p=0.009), adjuvant chemotherapy (p=0.039), positive resection margin (R) (p=0.018) and American Joint Committee for Cancer (AJCC) tumours above stage II (p=0.043). Significant uni-variate odds ratios (OR) were obtained for the same factors. Two linear logistic models were fitted as (1) N, M, R1 status and adjuvant chemotherapy and (2) AJCC stage, R1 status and adjuvant chemotherapy. From both models, the only factor significantly associated (p ≤ 0.01) with local recurrence was found to be a positive resection margin (OR 4.81 and 5.51 respectively). CONCLUSIONS: A positive resection margin is the single factor affecting local recurrence of rectal cancer in patients not receiving neo-adjuvant therapy.

Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: analysis of survival and prognostic markers.

OBJECTIVES: This study compares clinico-pathological features in young (<40 years) and older patients (>50 years) with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival. MATERIALS AND METHODS: A twelve year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models. RESULTS: Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05). In both groups, the majority presented without bowel obstruction (young--81%, older--94%). Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p < 0.05). Ninety four percent of young cancer deaths were within 20 months of operation. At median follow up of 50 months in the young, overall survival was 70% and disease free survival 66%. American Joint Committee on Cancer (AJCC) stage 4 and use of pre-operative chemoradiation in rectal cancer was associated with poor survival in the young. CONCLUSION: If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.

Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses.

The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent DbNP366 and DbPA224 epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ KbPB1(703)+, CD8+ KbNS2(114)+, and CD8+ DbPB1-F2(62)+ T cells were found in the spleen and in the inflammatory population recovered by bronchoalveolar lavage from mice that were first given the -NP-PA H1N1 virus intraperitoneally and then challenged intranasally with the homologous H3N2 virus. The effect was less consistent when this prime-boost protocol was reversed. Also, though the quality of the response measured by cytokine staining showed some evidence of modification when these minor CD8+-T-cell populations were forced to play a more prominent part, the effects were relatively small and no consistent pattern emerged. The magnitude of the enhanced clonal expansion following secondary challenge suggested that the prime-boost with the -NP-PA viruses gave a response overall that was little different in magnitude from that following comparable exposure to the unmanipulated viruses. This was indeed shown to be the case when the total response was measured by ELISPOT analysis with virus-infected cells as stimulators. More surprisingly, the same effect was seen following primary challenge, though individual analysis of the CD8+ KbPB1(703)+, CD8+ KbNS2(114)+, and CD8+ DbPB1-F2(62)+ sets gave no indication of compensatory expansion. A possible explanation is that novel, as yet undetected epitopes emerge following primary exposure to the -NP-PA deletion viruses. These findings have implications for both natural infections and vaccines.

Replication and interaction of herpes simplex virus and human papillomavirus in differentiating host epithelial tissue.

We have investigated the interactions and consequences of superinfecting and coreplication of human papillomavirus (HPV) and herpes simplex virus (HSV) in human epithelial organotypic (raft) culture tissues. In HPV-positive tissues, HSV infection and replication induced significant cytopathic effects (CPE), but the tissues were able to recover and maintain a certain degree of tissue integrity and architecture. HPV31b not only maintained the episomal state of its genomic DNA but also maintained its genomic copy number even during times of extensive HSV-induced CPE. E2 transcripts encoded by HPV31b were undetectable even though HPV31b replication was maintained in HSV- infected raft tissues. Expression of HPV31b oncogenes (E6 and E7) was also repressed but to a lesser degree than was E2 expression. The extent of CPE induced by HSV is dependent on the magnitude of HPV replication and gene expression at the time of HSV infection. During active HSV infection, HPV maintains its genomic copy number even though genes required for its replication were repressed. These studies provide new insight into the complex interaction between two common human sexually transmitted viruses in an in vitro system, modeling their natural host tissue in vivo.

Analysis of Patterns of Pineapple Mealybug Wilt Disease in Sri Lanka.

Mealybug wilt disease of pineapple has a complicated etiology, which is not yet fully understood. As a result, assessments of the disease in the field, such as those that are made in the context of evaluation of disease control methods, are usually based on symptomatology. Field assessments, based on symptoms of mealybug wilt disease, were made in the Kurunegala and Gampaha districts of Sri Lanka. These data were fitted to statistical probability distributions as a method of summarizing the spatial pattern of disease incidence. Most plots showed aggregated patterns of diseased plants, but there were some exceptions. Summarizing patterns of disease incidence by means of fitting statistical probability distributions provides a basis for significance testing in cases where factors affecting disease incidence are the subject of field experimentation. Some examples of this methodology are given.