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  1. Aliyu IA, Kumurya AS, Bala JA, Yahaya H, Saidu H
    Rev Med Virol, 2021 Sep;31(5):1-9.
    PMID: 33314425 DOI: 10.1002/rmv.2202
    Filopodia are thin finger-like protrusions at the surface of cells that are internally occupied with bundles of tightly parallel actin filaments. They play significant roles in cellular physiological processes, such as adhesion to extracellular matrix, guidance towards chemo-attractants and in wound healing. Filopodia were recently reported to play important roles in viral infection including initial viral attachment to host cells, cell surfing, viral trafficking, internalization, budding, virus release and spread to other cells in a form that would avoid the host immune system. The detailed virus-host protein interactions underlying most of these processes remain to be elucidated. This review will describe some reported virus-host protein interactions on filopodia with the aim of identifying potential new anti-virus therapeutic targets. Exploring this research area may lead to the development of novel classes of anti-viral therapeutics that can block signalling pathways used by the virus to trigger filopodia formation. Successful compounds would inhibit initial virus attachment, formation of filopodia, expression of putative virus binding protein, extracellular virus trafficking, and budding.
  2. Hambali NA, Yahaya H, Mahmood MR, Terasako T, Hashim AM
    Nanoscale Res Lett, 2014;9(1):609.
    PMID: 25411567 DOI: 10.1186/1556-276X-9-609
    The electrochemical growth of zinc oxide (ZnO) nanostructures on graphene on glass using zinc nitrate hexahydrate was studied. The effects of current densities and temperatures on the morphological, structural, and optical properties of the ZnO structures were studied. Vertically aligned nanorods were obtained at a low temperature of 75°C, and the diameters increased with current density. Growth temperature seems to have a strong effect in generating well-defined hexagonal-shape nanorods with a smooth top edge surface. A film-like structure was observed for high current densities above -1.0 mA/cm(2) and temperatures above 80°C due to the coalescence between the neighboring nanorods with large diameter. The nanorods grown at a temperature of 75°C with a low current density of -0.1 mA/cm(2) exhibited the highest density of 1.45 × 10(9) cm(-2). X-ray diffraction measurements revealed that the grown ZnO crystallites were highly oriented along the c-axis. The intensity ratio of the ultraviolet (UV) region emission to the visible region emission, I UV/I VIS, showed a decrement with the current densities for all grown samples. The samples grown at the current density below -0.5 mA/cm(2) showed high I UV/I VIS values closer to or higher than 1.0, suggesting their fewer structural defects. For all the ZnO/graphene structures, the high transmittance up to 65% was obtained at the light wavelength of 550 nm. Structural and optical properties of the grown ZnO structures seem to be effectively controlled by the current density rather than the growth temperature. ZnO nanorod/graphene hybrid structure on glass is expected to be a promising structure for solar cell which is a conceivable candidate to address the global need for an inexpensive alternative energy source.
  3. Lokman MQ, Shafie S, Shaban S, Ahmad F, Jaafar H, Mohd Rosnan R, et al.
    Materials (Basel), 2019 Jun 30;12(13).
    PMID: 31262020 DOI: 10.3390/ma12132111
    This study investigated the different thicknesses of TiO2 photoanode films and the effect of surface plasmon resonance (SPR) of Ag-TiO2 nanocomposites on the current-voltage (I-V) performance of dye-sensitized solar cells (DSSC). The TiO2 layer was deposited using the doctor blade technique and the thickness of the TiO2 films was controlled by using a different number of Scotch tape layers. The silver nanoparticles (AgNP) were synthesised using a chemical reduction method and the concentration of sodium citrate as a reducing agent was varied from 4 to 12 mM to study the effect of citrate ion on the size of the nanoparticles. Ag-TiO2 nanopowder was prepared by adding pure anatase TiO2 powder into AgNP colloidal solution. The mixture was left to dry for 24 h to obtain Ag-TiO2 powder for paste preparation. The three-layer Scotch tape, with thickness of 14.38 µm, achieved a high efficiency of 4.14%. This results showed that three layers was the optimal thickness to improve dye loading and to reduce the charge recombination rate. As for the Ag-TiO2 nanocomposites, 10 mM of AgNP, with a mean diameter of 65.23 nm and high efficiency of 6.92%, proved that SPR can enhance the absorption capability of dye and improve the photon-to-electron generation.
  4. Aris A, Khalid MZM, Yahaya H, Yoong LO, Ying NQ
    Curr Diabetes Rev, 2020;16(4):387-394.
    PMID: 31433762 DOI: 10.2174/1573399815666190712192527
    BACKGROUND: Type 2 diabetes (T2D) is a preventable condition. Targeting those who are at risk of getting this disease is essential.

    OBJECTIVE: To examine T2D risk among university students in Malaysia and determine its relationship with socio-demographic characteristics and physical activity.

    METHODS: The study was conducted cross-sectionally on 390 students selected using quota sampling method from 13 faculties in Universiti Kebangsaan Malaysia. A short form of the International Physical Activity Questionnaire and Finnish Diabetes Risk Score were used to measure the physical activity and T2D risk.

    RESULTS: The T2D risk was found to be low (M = 5.23, SD = 3.32) with more than two-third of the student population at the low risk level while a significant proportion of 23.8%, 5.6% and 0.3% having slightly elevated, moderate and high risk respectively. The T2D risk was significantly related to their age (rho = 0.197, p < 0.000), gender (U = 12641, p = 0.011), ethnic group (Χ2 = 18.86, p < 0.000), marital status (Χ2 = 6.597, p = 0.037), residence (U = 10345, p = 0.008), academic year (Χ2 = 14.24, p = 0.007) and physical activity (rho = -0.205, p < 0.000 and Χ2 = 13.515, p = 0.001). Of these, only age (β=0.130) and physical activity (β=-0.159) remained significant in the regression analysis.

    CONCLUSION: The findings call for a radical change in the nursing practice to target the amendable factors that are significant in order to prevent the progression of the risk towards type 2 diabetes.
  5. Mohd Putera NWS, Azman AS, Mohd Zain SN, Yahaya H, Lewis JW, Sahimin N
    Trop Biomed, 2023 Jun 01;40(2):138-151.
    PMID: 37650399 DOI: 10.47665/tb.40.2.003
    The mass movement of migrants to Malaysia for employment is one of the factors contributing to the emergence and re-emergence of infectious diseases in this country. Despite mandatory health screening for migrants seeking employment, prevalence records of infectious diseases amongst migrant populations in Malaysia are still within negligible proportions. Therefore, the present review highlights the incidence, mortality and overall status of infectious diseases amongst migrants' populations in Malaysia, which maybe be useful for impeding exacerbation of inequalities among them and improving our national health system thru robust and effective emergency responses in controlling the prevalent diseases found among these populations and maybe, Malaysian citizens too. Peer-reviewed articles from January 2016 to December 2020 were searched through online platform including SCOPUS, PubMed, Science Direct, and Google Scholar. Non-peer-reviewed reports and publications from ministry and government websites including data from related agencies were also scoured from in order to ensure that there are no cases being overlooked, as most published articles did not have migrants as the research subjects. A total of 29 studies had been selected in the final analysis. Migrants in Malaysia were at higher risk for tuberculosis, malaria, lymphatic filariasis, cholera, leprosy and leptospirosis. Lymphatic filariasis was still endemic among this population while thousand cases of TB and cholera had been reported among them due to cramp living conditions and poor sanitation in their settlements respectively. While malaria had gradually decreased and become sporadic, the influx of migrant workers had led to the rising of imported malaria cases. Low cases of leprosy had been recorded in Malaysia but a significant proportion of it was contributed by migrant workers. As for leptospirosis, studies found that there are prominent cases among migrant workers, which particularly highest within workers with lower educational attainment. Infectious diseases are still prevalent among migrants in Malaysia due to various interplay factors including their working sectors, country of origin, immunization status, type of settlement, impoverished living conditions, and language and cultural barriers that impeding access to health facilities.
  6. Jayah NA, Yahaya H, Mahmood MR, Terasako T, Yasui K, Hashim AM
    Nanoscale Res Lett, 2015;10:7.
    PMID: 25852306 DOI: 10.1186/s11671-014-0715-0
    Hydrothermal zinc oxide (ZnO) thick films were successfully grown on the chemical vapor deposition (CVD)-grown thick ZnO seed layers on a-plane sapphire substrates using the aqueous solution of zinc nitrate dehydrate (Zn(NO3)2). The use of the CVD ZnO seed layers with the flat surfaces seems to be a key technique for obtaining thick films instead of vertically aligned nanostructures as reported in many literatures. All the hydrothermal ZnO layers showed the large grains with hexagonal end facets and were highly oriented towards the c-axis direction. Photoluminescence (PL) spectra of the hydrothermal layers were composed of the ultraviolet (UV) emission (370 to 380 nm) and the visible emission (481 to 491 nm), and the intensity ratio of the former emission (I UV) to the latter emission (I VIS) changed, depending on both the molarity of the solution and temperature. It is surprising that all the Hall mobilities for the hydrothermal ZnO layers were significantly larger than those for their corresponding CVD seed films. It was also found that, for the hydrothermal films grown at 70°C to 90°C, the molarity dependences of I UV/I VIS resembled those of mobilities, implying that the mobility in the film is affected by the structural defects. The highest mobility of 166 cm(2)/Vs was achieved on the hydrothermal film with the carrier concentration of 1.65 × 10(17) cm(-3) grown from the aqueous solution of 40 mM at 70°C.
  7. Sahimin N, Low ZX, Hassandarvish P, Mohd Hanapi IR, Mohd Zain SN, Yahaya H, et al.
    Trans R Soc Trop Med Hyg, 2024 May 01;118(5):328-335.
    PMID: 38226501 DOI: 10.1093/trstmh/trad097
    BACKGROUND: Mosquito-borne diseases pose a significant global public health threat, with Malaysia's Klang Valley experiencing numerous outbreaks in densely populated urban areas.

    METHODS: This study aimed to estimate the seroprevalence of anti-dengue and anti-chikungunya antibodies among urban refugees in the Klang Valley, Malaysia, and identify associated risk factors.

    RESULTS: High seroprevalence of anti-dengue immunoglobulin G (IgG) and IgM (60.0% [confidence interval {CI} 55.39 to 64.48] and 9.2% [CI 6.77 to 12.25], respectively) were observed among refugees >18 years of age (χ22=11.720, p=0.003), Kachin ethnicity (χ28=72.253, p<0.001), without formal education (χ21=3.856, p=0.050), homes near waste disposal sites (χ21=10.378, p=0.001) and refugees who have experienced flooding (χ21=5.460, p=0.019). Meanwhile, the overall seroprevalence of anti-chikungunya IgG and IgM was 9.7% (CI 7.15 to 12.73) and 10.8% (CI 8.09 to 13.93), respectively, with ages 12-18 years (χ22=6.075, p=0.048), Rohingya ethnicity (χ28=31.631, p<0.001) and homes close to waste disposal sites (χ21=3.912, p=0.048) being significant risk factors. Results showed a link to poor environmental living conditions, with an increase in the vector population with higher availability of breeding sites and thus exposure to dengue and chikungunya virus.

    CONCLUSIONS: Health education among the community is the key to disease prevention, as there are no specific antiviral drugs for treatment and limited vaccine availability.

  8. Zuikafly SNF, Ahmad H, Ismail MF, Abdul Rahman MA, Yahya WJ, Abu Husain N, et al.
    Micromachines (Basel), 2023 May 14;14(5).
    PMID: 37241671 DOI: 10.3390/mi14051048
    We investigate the dynamics of high energy dual regime unidirectional Erbium-doped fiber laser in ring cavity, which is passively Q-switched and mode-locked through the use of an environmentally friendly graphene filament-chitin film-based saturable absorber. The graphene-chitin passive saturable absorber allows the option for different operating regimes of the laser by simple adjustment of the input pump power, yielding, simultaneously, highly stable and high energy Q-switched pulses at 82.08 nJ and 1.08 ps mode-locked pulses. The finding can have applications in a multitude of fields due to its versatility and the regime of operation that is on demand.
  9. Chew SY, Brown AJP, Lau BYC, Cheah YK, Ho KL, Sandai D, et al.
    J Biomed Sci, 2021 Jan 02;28(1):1.
    PMID: 33388061 DOI: 10.1186/s12929-020-00700-8
    BACKGROUND: Emergence of Candida glabrata, which causes potential life-threatening invasive candidiasis, has been widely associated with high morbidity and mortality. In order to cause disease in vivo, a robust and highly efficient metabolic adaptation is crucial for the survival of this fungal pathogen in human host. In fact, reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection.

    METHODS: In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches.

    RESULTS: Collectively, a total of 1482 transcripts (26.96%) and 242 proteins (24.69%) were significantly up- or down-regulated. Both transcriptome and proteome data revealed that the regulation of alternative carbon metabolism in C. glabrata resembled other fungal pathogens such as Candida albicans and Cryptococcus neoformans, with up-regulation of many proteins and transcripts from the glyoxylate cycle and gluconeogenesis, namely isocitrate lyase (ICL1), malate synthase (MLS1), phosphoenolpyruvate carboxykinase (PCK1) and fructose 1,6-biphosphatase (FBP1). In the absence of glucose, C. glabrata shifted its metabolism from glucose catabolism to anabolism of glucose intermediates from the available carbon source. This observation essentially suggests that the glyoxylate cycle and gluconeogenesis are potentially critical for the survival of phagocytosed C. glabrata within the glucose-deficient macrophages.

    CONCLUSION: Here, we presented the first global metabolic responses of C. glabrata to alternative carbon source using transcriptomic and proteomic approaches. These findings implicated that reprogramming of the alternative carbon metabolism during glucose deprivation could enhance the survival and persistence of C. glabrata within the host.

  10. Che-Kamaruddin N, Hamid NFS, Idris LH, Yusuff FM, Ashaari ZH, Yahaya H, et al.
    Vet Parasitol Reg Stud Reports, 2024 Apr;49:100998.
    PMID: 38462308 DOI: 10.1016/j.vprsr.2024.100998
    Fasciolosis is a zoonotic disease, considered an emerging neglected tropical disease threatening ruminant productivity and causing economic losses. Controlling fasciolosis is challenging due to the complex life cycle of Fasciola, which involves snail intermediate hosts. The high rainfall status in Taiping makes it an optimal region for snail abundance, which increases the opportunity to complete Fasciola's life cycle. Previous studies showed that liver condemnation caused by fasciolosis was highly prevalent in the Taiping abattoir compared to other investigated main abattoirs of Peninsular Malaysia. Therefore, the present study determined the prevalence of bovine fasciolosis and risk factors in farms from Larut and Matang (Taiping), Malaysia. Sampling was carried out from February until August 2020. In this cross-sectional study, a total of 371 fecal samples from bovines (dairy cattle, beef cattle, buffalo) were examined from 23 farms selected based on location, farmer consent, and history of anthelmintic usage. Animal's intrinsic and farm management details were recorded, and interview sessions were conducted with farmers to collect information on the potential risk factors. Individual fecal samples were examined for the presence of Fasciola egg using Flukefinder® sedimentation. There was moderate prevalence of bovine fasciolosis in Taiping (36.9%, n = 137/371). Significant risk factors (p 3 years (OR = 5.5, 95% CI: 5.43-5.57), thinner animals with body condition score of 1 to 4 (OR = 1.2-14.9, 95% CI: 1.09-15.08), and larger grazing area (OR = 1.3, 95% CI: 1.30-1.31). Additional risk factors include the presence of more than one ruminant species in the same farm (OR = 2.0-2.1, 95% CI: 2.00-2.22), extensive housing system (OR = 4.0, 95% CI: 3.77-4.23), farm age (OR = 1.2, 95% CI: 1.20-1.21), and also co-infection with Paramphistomes (OR = 1.4, 95% CI: 1.10-1.71). The present study underscores the importance of local bovine fasciolosis epidemiology, which could be used to conduct future veterinary and public health programmes to inform effective parasitic management aimed at reducing the prevalence of fasciolosis.
  11. Ahmad Zamzuri M'I, Abd Majid FN, Mihat M, Ibrahim SS, Ismail M, Abd Aziz S, et al.
    PMID: 36833715 DOI: 10.3390/ijerph20043021
    INTRODUCTION: Primary amoebic meningoencephalitis (PAM) is a rare but lethal infection of the brain caused by a eukaryote called Naegleria fowleri (N. fowleri). The aim of this review is to consolidate the recently published case reports of N. fowleri infection by describing its epidemiology and clinical features with the goal of ultimately disseminating this information to healthcare personnel.

    METHODS: A comprehensive literature search was carried out using PubMed, Web of Science, Scopus, and OVID databases until 31 December 2022 by two independent reviewers. All studies from the year 2013 were extracted, and quality assessments were carried out meticulously prior to their inclusion in the final analysis.

    RESULTS: A total of 21 studies were selected for qualitative analyses out of the 461 studies extracted. The cases were distributed globally, and 72.7% of the cases succumbed to mortality. The youngest case was an 11-day-old boy, while the eldest was a 75-year-old. Significant exposure to freshwater either from recreational activities or from a habit of irrigating the nostrils preceded onset. The symptoms at early presentation included fever, headache, and vomiting, while late sequalae showed neurological manifestation. An accurate diagnosis remains a challenge, as the symptoms mimic bacterial meningitis. Confirmatory tests include the direct visualisation of the amoeba or the use of the polymerase chain reaction method.

    CONCLUSIONS: N. fowleri infection is rare but leads to PAM. Its occurrence is worldwide with a significant risk of fatality. The suggested probable case definition based on the findings is the acute onset of fever, headache, and vomiting with meningeal symptoms following exposure to freshwater within the previous 14 days. Continuous health promotion and health education activities for the public can help to improve knowledge and awareness prior to engagement in freshwater activities.

  12. Suah JL, Tok PSK, Ong SM, Husin M, Tng BH, Sivasampu S, et al.
    Vaccines (Basel), 2021 Nov 24;9(12).
    PMID: 34960126 DOI: 10.3390/vaccines9121381
    Malaysia rolled out a diverse portfolio of predominantly three COVID-19 vaccines (AZD1222, BNT162b2, and CoronaVac) beginning 24 February 2021. We evaluated vaccine effectiveness with two methods, covering 1 April to 15 September 2021: (1) the screening method for COVID-19 (SARS-CoV-2) infection and symptomatic COVID-19; and (2) a retrospective cohort of confirmed COVID-19 cases for COVID-19 related ICU admission and death using logistic regression. The screening method estimated partial vaccination to be 48.8% effective (95% CI: 46.8, 50.7) against COVID-19 infection and 33.5% effective (95% CI: 31.6, 35.5) against symptomatic COVID-19. Full vaccination is estimated at 87.8% effective (95% CI: 85.8, 89.7) against COVID-19 infection and 85.4% effective (95% CI: 83.4, 87.3) against symptomatic COVID-19. Among the cohort of confirmed COVID-19 cases, partial vaccination with any of the three vaccines is estimated at 31.3% effective (95% CI: 28.5, 34.1) in preventing ICU admission, and 45.1% effective (95% CI: 42.6, 47.5) in preventing death. Full vaccination with any of the three vaccines is estimated at 79.1% effective (95% CI: 77.7, 80.4) in preventing ICU admission and 86.7% effective (95% CI: 85.7, 87.6) in preventing deaths. Our findings suggest that full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in Malaysia has been highly effective in preventing COVID-19 infection, symptomatic COVID-19, COVID-19-related ICU admission, and death.
  13. Johari J, Hontz RD, Pike BL, Husain T, Rusli N, Mohd-Zain R, et al.
    Emerg Microbes Infect, 2023 Dec;12(1):2208678.
    PMID: 37101375 DOI: 10.1080/22221751.2023.2208678
    Prospective cohort study to investigate the potential exposure to the Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) following Hajj pilgrims is still very limited. Here, we report the antibody seroconversion study results obtained from successive three years cohort studies (2016-2018) involving the Malaysian Hajj pilgrims returning from the Middle East. A cohort study of Hajj pilgrims from Malaysia enrolled 2,863 participants from 2016-2018, all of whom consented to provide paired blood samples for both pre- and post-Hajj travel to the Middle East. ELISAs and micro-neutralization assays were performed to detect the presence of MERS-CoV IgG antibodies. Sociodemographic data, symptoms experienced during Hajj, and history of exposure to camels or camel products were recorded using structured pre- and post-Hajj questionnaires. A 4-fold increase in anti-MERS-CoV IgG between paired pre-Hajj and post-Hajj serum samples in twelve participants was observed. None of the twelve ELISA-positive sera had detectable levels of virus-neutralizing antibodies. All reportedly had mild symptoms of respiratory symptoms at a certain point during the pilgrimage, implying mild or asymptomatic infections. No association between post-Hajj serum positivity and a history of exposure to camels or camel products was obtained. Findings from the study suggest that serologic conversion to MERS-CoV occurred in at least 0.6% of the Hajj pilgrims returning from the Middle East. Since all the seroconvertants had mild to no symptoms during the sampling period, it highlights the likelihood of occurrence of only low infectivity spillover infections among the Hajj pilgrims.
  14. Emeribe AU, Dangana A, Isa HA, Onoja SO, Otu TO, Ibrahim Y, et al.
    Biomedicine (Taipei), 2022;12(1):1-13.
    PMID: 35836914 DOI: 10.37796/2211-8039.1237
    BACKGROUND: Despite the efforts to encourage the intake of nutritional supplements during antenatal periods, there are still many cases of anemia and protein-energy malnutrition during pregnancy. Hence, this study determined the incidence of anemia, protein-energy malnutrition, and associated risk factors among pregnant women in Abuja, Nigeria.

    MATERIALS AND METHODS: This hospital-based, case-control study involved randomly selected 176 pregnant and non-pregnant women attending the University of Abuja Teaching Hospital (UATH), Gwagwalada, Nigeria. Hemoglobin and hematocrit measurements were used to determine anemia incidence, while plasma protein, zinc levels and body mass index (BMI) were used to determine energy index status. Complete blood counts were analyzed using 5 parts-automatic hemo-analyzer, while plasma protein and zinc were analyzed using calorimetric method. Anemia and protein-energy malnutrition were defined using the World Health Organization (WHO) cut-off values.

    RESULTS: The mean age of participants was 28.75 ± 5.22 years. Out of 176 participants, 7 (4%) were malnourished while 25% of the participants were anemic. Anemia was significantly associated with participants' occupation (p = 0.002), parity (p<0.001) and gestational age (p<0.001). Most hematological indices, plasma globulin, albumin, protein, and zinc levels were significantly different (p<0.001) among non-pregnant and pregnant women of the first, second and third trimesters.

    CONCLUSION: The incidence of anemia and malnutrition was high among study participants. There is a need for improved nutritional intervention, increased awareness and strengthening of health systems in the area of maternal health in Nigeria.

  15. Johari J, Hontz RD, Pike BL, Husain T, Chong CK, Rusli N, et al.
    BMJ Open, 2021 08 26;11(8):e050901.
    PMID: 34446498 DOI: 10.1136/bmjopen-2021-050901
    INTRODUCTION: Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by the MERS-CoV. MERS was first reported in the Kingdom of Saudi Arabia in 2012. Every year, the Hajj pilgrimage to Mecca attracts more than two million pilgrims from 184 countries, making it one of the largest annual religious mass gatherings (MGs) worldwide. MGs in confined areas with a high number of pilgrims' movements worldwide continues to elicit significant global public health concerns. MERCURIAL was designed by adopting a seroconversion surveillance approach to provide multiyear evidence of MG-associated MERS-CoV seroconversion among the Malaysian Hajj pilgrims.

    METHODS AND ANALYSIS: MERCURIAL is an ongoing multiyear prospective cohort study. Every year, for the next 5 years, a cohort of 1000 Hajj pilgrims was enrolled beginning in the 2016 Hajj pilgrimage season. Pre-Hajj and post-Hajj serum samples were obtained and serologically analysed for evidence of MERS-CoV seroconversion. Sociodemographic data, underlying medical conditions, symptoms experienced during Hajj pilgrimage, and exposure to camel and untreated camel products were recorded using structured pre-Hajj and post-Hajj questionnaires. The possible risk factors associated with the seroconversion data were analysed using univariate and multivariate logistic regression. The primary outcome of this study is to better enhance our understanding of the potential threat of MERS-CoV spreading through MG beyond the Middle East.

    ETHICS AND DISSEMINATION: This study has obtained ethical approval from the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia. Results from the study will be submitted for publication in peer-reviewed journals and presented in conferences and scientific meetings.

    TRIAL REGISTRATION NUMBER: NMRR-15-1640-25391.

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