Qatar Foundation Annual Research Forum Volume 2011 Issue 1

Background: Body core temperature fluctuates during the day following a sinusoidal variation with a maximum acrophase in the late afternoon. This circadian rhythm is mainly endogenous but it can be influenced by environmental factors such as work and social and physical activities.

Objectives: 1) To verify if aluminum shift-workers would present different core temperatures at different times of the day (i.e. diurnal variations); 2) To characterize these diurnal variations and their consequences.

Methods: Twenty-nine employees from the aluminum industry participated in this preliminary study. They worked indoors where the temperature was typically in excess of 40°C. In addition, each worker wore protective clothing consisting of suit, gloves and mask. Core temperature (ingestible pill) data covering a 24-hour circadian cycle were obtained in 10 workers during morning, afternoon and night shifts. Circadian variation in temperature was characterized using a cosinus function (cosinor model). The mesor (average) and acrophase of the function have been calculated for each participant.

Results: Core temperatures recorded on the work site were significantly higher in the afternoon or early evening (from 12:00h to 20:00h) than at night or during the early morning (from 21:00h to 08:00h). These differences were not triggered by the work duration but by the time of day. There were large differences between the individual accrophase times, probably due to different working activities as well as the influence of synchronization/shift from the previous days. However, core temperature was consistently higher in the afternoon than during the morning or night. The circadian variation in body core temperature showed a mesor of 37.45°C. This represents an average core temperature half a degree higher than generally observed in the general population at rest.

Conclusions: The current data showed that workers from the aluminum industry present a relatively elevated average core temperature, with the highest values being reached during the afternoon shift. This suggests that special attention should be given to the afternoon shift and that break/cooling procedures should be implemented if necessary. These preliminary observations have to be completed by clinical and behavioral observations.

Background: Schoolchildren must practice healthy diet as well as active lifestyle to support their physical growth and development. Previous studies have shown that intermittent fasting can affect dietary intake, sleep duration and circadian patterns among adults, but there is a lack of related literature in schoolchildren.

Purpose: The aim of this study was to objectively assess the effect of Ramadan fasting on physiological parameters in young children.

Methods: Eighteen boys aged 12.6±1.5 years were assessed at baseline (BR) and followed up twice during Ramadan (1st week [R1], 4th week [R4]) and once two weeks after the end of Ramadan (AR). Body composition was assessed using anthropometry and DXA scan. Blood investigations included complete blood count, lipid profile analysis and iron indices. Pattern of daily activity and core body temperature were recorded using a triaxial accelerometer and ingestible thermistor pill, respectively. Dietary intake was assessed by experienced nutritionist based on digital images of food and drinks consumed by each participant during a 24-hour period. Repeated sprints tests (RSA) of 6 × 15 m sprints interspaced by 15 s rest were performed to evaluate fatigue resistance.

Results: There was a shift in daily peak activity from daytime (5:30 PM) to late night (12:00 AM) that resulted in 1.8±0.6 hours of loss in total sleep time during R4 (P<0.01). After 30 days of fasting there were no important change in lipids, but a significant drop in serum iron from 17.7±1.6 μmol/L at BR to 13.1±1.4 μmol/L (P<0.01), suggesting a potential nutritional deficiency. Moreover, reduction in serum iron was associated with younger age (r=0.47, P=0.05) and lighter body weight (r=0.37, P=0.13). Dietary analysis showed that subjects consumed a high calorific diet deficient in fruits and vegetables during Ramadan that explains weight gain (+1.0±0.2 kg, P=0.001) and consequently longer sprint times on RSA test (+0.4±0.1 s, P=0.04) at R4 compared to baseline.

Conclusion: This study concludes that intermittent Ramadan fasting may have an undesirable impact on body composition, sleep patterns and nutritional habits in young schoolchildren. These results could be used to develop educational strategies to promote a healthy lifestyle in schoolchildren during Ramadan.

Background: Exercise-induced hyperthermia is associated with a decrease in force production capacity during brief (<5 seconds) and sustained (>10 seconds) maximal voluntary isometric contractions (MVIC). A reduction in central nervous system drive to exercising muscles is suggested to mediate this decrement to prevent thermal injury. Until recently, the influence of exercise modality on neuromuscular function in the heat remained unclear. Two studies have since elucidated the role of constant load and self-paced exercise on force production capacity and voluntary activation during hyperthermia.

Methods: Study one evaluated neuromuscular function after a 40 km cycling time trial in hot (35°C) and cool conditions (20°C). In study two, muscle function was evaluated after passive heating via water immersion to a core temperature of 39.5°C and following constant load exercise to exhaustion at 60% of maximal oxygen uptake (38°C conditions). Prior to (control) and following each intervention, a sustained MVIC (20 s and 45 s, respectively for study 1 and 2) was performed to measure force production. Voluntary activation of the knee extensors was measured via percutaneous electrical stimulation at three intervals during each MVIC.

Results: Following self-paced exercise, mean force production decreased similarly in hot (15%) and cool (14%) conditions compared with control, despite a difference in core temperature of 0.8°C (P<0.001). A reduction in mean voluntary activation (P<0.05) accounted for ∼20% of the decrement in force. Interestingly, the extent of decline in voluntary activation was sustained for the duration of MVIC and did not progressively decrease. In the second study, mean force production was reduced following both interventions, but the magnitude of decline was more pronounced after exercise (P<0.05). As with study one, the decline in voluntary activation was similarly maintained (∼93%) following both interventions, with central fatigue accounting for <45% of the loss in force.

Conclusion: The loss of force production following exercise-induced hyperthermia appears to stem for both central and peripheral fatigue factors. Modality does not appear to influence neuromuscular function when exercise duration is similar and final core temperature is within ∼1°C. The combination of exercise and heat stress exacerbates the loss of force due to prior contractile activity.

Sleep spindles, along with K-complexes are hallmarks of stage 2 non rapid eye movement (NREM) sleep EEG. Sleep spindles are of significant interest because they are associated with phenomena such as ‘stability’ of sleep, updating of knowledge with new memories, processing of sensorimotor and mnemonic information. Therefore, accurately marking their presence in sleep recordings is essential.

Accurate identification of spindles in EEG recordings has proved to be a time consuming task, even with the help of experts. Further, manual detection by different experts introduces disparity and biases due to inter-rater differences. Hence there is a crucial need for an automated detection algorithm.

The objective of this paper was to develop a robust algorithm for real-time automated spindle detection based on the wavelet packet decomposition. The developed algorithm replicates the marking methodology used by sleep specialists to identify spindles. Spindles are transient 11–16 Hz oscillations present in NREM with higher amplitude than the background delta waves. To identify the spindles the EEG data was divided into epochs from which appropriate features were extracted to differentiate spindles from the background EEG. The feature vectors used included the level of EOG activity, the quantity of significant peak-to-peak transitions, the wavelet packet energy (WPE) within the frequency band of interest (11–16 Hz) and the presence of K-complexes. EOG activity was tracked to identify NREM sleep sections. Spindles were marked as being present in those epochs in which the WPE and peak-to-peak activity were higher than predetermined thresholds. The thresholds were reduced on detection of K-complexes, mimicking manual scoring.

The accuracy of the developed algorithm was verified by comparing to the manual scoring performed by a sleep specialist on the EEG data. The results from the algorithm look promising with a good degree of agreement with the manual scoring. When run on 3 hours of EEG data with 52 manually scored spindles the algorithm successfully detected 42 of them (80.7%) and of the total 21,600 epochs analyzed 290 were falsely detected as containing spindles. It was also observed that the true detection rate increases on varying the thresholds although this introduces further false detections.

Intorduction: Posaconazole (PZ), an antifungal prophylactic therapy in hematologic cancer patients, was added to Al-Amal Hospital formulary in 2010. The objectives of this study are: 1. To identify the practice guidelines and pharmacokinetics information regarding PZ use in Qatar and worldwide. 2. To conduct a drug use evaluation (DUE) report at Al-Amal Hospital.

Methods: Literature review was conducted to answer the first objective. A retrospective DUE report was conducted to include 10 randomly chosen hematologic cancer patients who used PZ during the year 2010. Patients profiles were reviewed and data were collected into a pre-prepared collection sheet.

Results: PZ was approved for prophylaxis in hematologic cancer patients →13 years in USA, Canada, and Australia, →18 years in the European Union and >15 years in Qatar. PZ has low bioavailability that can be enhanced by co-administration of high fat meals and by dividing the total daily dose. Data regarding PZ TDM is controversial. PZ undergoes several drug-drug interactions. For example, co-administration of proton pump inhibitors may result in PZ sub-therapeutic levels. Co-administration of vincristine may result in higher neurological toxicity, mainly gastrointestinal problems, due to the inhibitory potency of PZ on cytochrome P450 enzymes. A patient receiving vincristine based chemotherapy protocol concurrently with PZ developed seizure. Another patient developed mild breakthrough fungal infection while on PZ prophylactically.

Conclusion: The PZ regulations in Qatar are similar to the worldwide recommendations. The PZ practice in Al-Amal hospital abides by the regulations. Possible serious PZ drug-drug interactions, seizures, in hematologic cancer patients should be highlighted and carefully monitored.

Background: Despite the efficacy of IM in treating CML, high degree of resistance has already been noted.

AGP may reduce drug efficacy through its ability to interact with IM.

Objectives: Could the level of AGP be correlated with CML resistance/response to treatment and if it could be employed as a biological marker for CML resistance.

Methods: 25 CML patients were investigated for AGP level, serum samples were analysed to determine AGP level. Immunoturbidimetric assay is based on the formation of a precipitate of AGP with a specific antiserum. The mean, variance and significant difference between the means were determined using Student's t test and significance was determined when p value was ←0.05.

Results: Over 2 years a total of 89 serum samples were collected from 25 CML patients treated at Al Amal hospital in Qatar. Ten samples from 10 healthy volunteers were collected as a control group.

9 patients presented with CML at Chronic Phase (CP), 5 at Accelerated Phase (AP), 6 patients progressed while on treatment and five more patients were undergoing treatment and were at Complete Haematological Remission (CHR) at time of sample collection.

The mean AGP levels were 1.2 (±0.3), 1.61 (±0.4), 1.01 (±0.08), 1.07 (±0.09), and 0.72 (±0.04) for CP, AP, Poor Responders, CHR and controls respectively.

The mean AGP level for the control group was significantly lower when compared with any of the diseased group.

The significant differences amongst CP, AP, Poor Responders patients, CHR patients and control group were (p) 0.001, 0.03, 0.003, 0.005 respectively.

On the other hand, among these different CML groups there was no significant difference in AGP levels even when correlated with white blood cells, platelets and/or basophiles.

However, there was significant difference between CP and AP patients (P value 0.002) when AGP was correlated with WBC's.

Nonetheless AGP level could not be correlated with course of disease.

Conclusions: The noticed resistance in our CML patient population could not be correlated with AGP levels, as patients were responding or resisting treatment without any recognisable pattern of AGP; even when patients achieved CHR they might still had elevated AGP levels.

Back ground and Objectives: Vitamin D deficiency is very common in pregnant women and the current guidelines for vitamin D intake during pregnancy of 200-400 IU has been challenged recently .We conducted this study to determine the prevalence of Vitamin D deficiency among pregnant women and to evaluate the safety weekly oral 50,000 IU vitamin D supplementation for the mother and the newborn.

Setting and design: prospective study, at Hamad Medical Corporation, outpatient unit and delivery room.

Patients and Methods: 97 pregnant women were recruited in their first trimester between December 2007 and March 2010. Weekly oral vitamin D 50,000 IU were prescribed after an initial testing for serum level of 25-hydroxyvitaminD, parathyroid hormone, calcium, phosphorus, total protein and albumin. Other multivitamins supplementations were allowed during pregnancy. The same tests were repeated at each trimester. Umbilical cords Vitamin D levels were determined at birth. .

Results: Out of 97, 8 patients dropped out from the study for several reasons, and 19 patients had miscarriages.

Data were available for 97 women in the first trimester, 78 women in the second trimester and 61 women in the third trimester .The mean level of vitamin D in the first trimester and prior to starting vitamin D supplementation was 17.15ng/ml, 29.08 ng/ml in the second trimester, 27.3 ng/ml in third trimester and 22.36 ng/ml in newborns. There were no toxic levels of vitamin D in any of the women at second or third trimester or in the newborns. The mean levels of vitamin D in the second and third trimester were not significantly different in the women who were taking multivitamin supplementation versus those who were not.

Conclusion: Weekly dose of 50,000 vitamin D during pregnancy is safe in our population, maintains acceptable vitamin D level during pregnancy and the newborns' vitamin D level correlates with the mother's levels.

Background: Vitamin B12 (vit B12) deficiency is one of the major causes of megaloblastic anaemia and should be avoided as early as possible since a supplementation of mother and child can prevent neurological symptoms of the baby. Furthermore, the neurological symptoms of affected children are (partially) reversible. Elevated methylmalonic acid in urine and homocysteine (Hcy) in plasma are sensitive indicators. In the State of Qatar, extended newborn screening of classical homocystinuria was realized for all 73,994 neonates in last 4.5 years. Newborns with slightly elevated Hcy levels in dried blood spots (DBS) were followed up with regard to possible vit B12 deficiency. In addition, the propionylcarnitine (C3) levels were analysed.

Methods: Determination of Hcy in DBS was performed using liquid chromatography electrospray tandem mass spectrometry. C3 levels were obtained from general newborn screening. The vit B12 levels in plasma were analysed spectrophotometrically.

Results: In all, 117 cases with mildly elevated Hcy levels were found. 65 were diagnosed with vit B12 deficiency. Only 9 of these 65 newborns had abnormal C3 levels. No correlation was found in this group between Hcy and C3 levels.

Conclusion: Extended neonatal screening of Hcy is a useful tool for early diagnosis and treatment of vit B12 deficiency.

Background: Although open Ramsted's pyloromyotomy is the gold standard for the surgical management of infantile hypertrophic pyloric stenosis, laparoscopic pyloromyotomy has been found highly successful. Various factors, however, can affect the outcomes of surgical interventions in these patients. We observed a relationship between the number of ports used and outcome in patients undergoing laparoscopic pyloromyotomies.

Method: We retrospectively assessed the medical records of selected group of patients who underwent laparoscopic pyloromyotomy in our institution. Factors analyzed included operation time, length of hospital stay, postoperative complications, and time to postoperative full feeding.

Results: We observed failure of myotomy in both two patients who underwent laparoscopic pyloromyotomy using only two working ports compared to successful myotomies in the remaining patients.

Conclusion: Laparoscopy provides good results in terms of intraoperative exposure and cosmesis. However, standardized surgical technique with two working ports is advisable and this can trigger further research to be ascertained.

Population aging is a worldwide phenomenon, but its impact on Qatar is unique. The proposed system aims at comprehensive and integrated vital signs (ECG, Saturation of Arterial Oxygen (SpO2), BP and Heart rate (HR)) monitoring using a wearable sensor platform without professional involvements or interfering the elderly's everyday activities. A novel wireless physiological sensor node with single highly-integrated board has been specifically designed and fabricated ( Fig.1(a) ). The new board comprises of a MCU, ECG analog front-end, LED driver and brightness adjustment circuit for photoplethysmograph (PPG) measurement, a CC2420 chip for wireless communication and a FTDI FT232RL chip for MCU programming and real-time debugging. A miniaturized wireless gateway was also designed ( Fig.1(b) ) to wirelessly receive the data from sensor node and further relay to the PC for ongoing research on ECG denoising and arrhythmia classification.

A novel MEMS-based electrode has been designed and fabricated for ECG measurement as shown in Fig.2 . Compared with conventional ECG electrodes, micromachined electrode is more comfortable; no direct contact of gel with the human skin and imposes no side effects to human for continuous and long term measurement. A unique characteristic feature of the proposed electrode is that the microneedle array is made of heavily doped silicon, which is electrically conductive and eliminates the requirement to dope Ag/AgCl or metal layer on the microneedles for electric contact. The microneedles can directly pierce through the outer skin surface, lowering the electrode-skin-electrode impedance (ESEI) and eliminating the need for skin preparation which, is prerequisite for wet electrode. For long-term monitoring, mechanical failure of micro-needles may accidentally happen due to the axial loading during insertion process or transverse loading during the measurement. As a result, the broken silicon needles will become debris in the skin, which attracts healthy concern for the user. Therefore, critical buckling loads for fabricated micro-needle were investigated using both theoretical estimation and ANSYS simulation. The results show that the critical buckling load is much larger than theoretical insertion force thereby the buckling problem will not occur during the insertion process.

This work is supported by Qatar National Research Funding (QNRF) under the grant NPRP 09-292-2-113.