Improved HUMARA for the Detection of X-Linked Agammaglobulinemia Carriers.

Background: Fragment analysis of exon 1 of the human androgen receptor, known as HUMARA, is a polymerase chain reaction (PCR)-based method for detecting X-linked agammaglobulinemia (XLA) carriers. This method takes advantage of X-chromosome inactivation (XCI) in female cells. XLA is caused by mutations in the Bruton tyrosine kinase (BTK) gene, located in Xq22.1. In this study, XCI is nonrandom or skewed in B-cells. B-cells with an active X-chromosome carrying a BTK mutation do not mature. Peripheral B-cells in XLA carriers inactivate the mutated X-chromosome. Methods: HUMARA was performed using DNA from purified B-cells and total leukocytes. DNA was digested using methylation-sensitive HhaI. The PCR of the HUMARA polymorphic marker was performed with the HhaI digested samples. The lengths of the PCR products were determined. If a suspected carrier showed skewed XCI in their B-cells, the marker length that corresponded with the length determined in the index patient indicated their carrier status. Results: HUMARA was conducted on purified B-cells; this allowed easier identification of the mutated or inactive allele, as the active allele was enzymatically digested. Analysis of 30 possible carriers using modified HUMARA corroborated that the carrier status in all samples that were heterozygous for the marker using XCI calculation for leukocytes showed a Gaussian distribution, while the carrier B-cell DNA showed a skewed XCI. Conclusion: Carrier status was successfully determined for most of the analyzed samples. B-cell enrichment resulted in precise carrier determination data, reduced the sample size, and facilitated inactive and active allele identification.

Hemodynamics Challenges for the Navigation of Medical Microbots for the Treatment of CVDs.

Microbots have been considered powerful tools in minimally invasive medicine. In the last few years, the topic has been highly studied by researchers across the globe to further develop the capabilities of microbots in medicine. One of many applications of these devices is performing surgical procedures inside the human circulatory system. It is expected that these microdevices traveling along the microvascular system can remove clots, deliver drugs, or even look for specific cells or regions to diagnose and treat. Although many studies have been published about this subject, the experimental influence of microbot morphology in hemodynamics of specific sites of the human circulatory system is yet to be explored. There are numerical studies already considering some of human physiological conditions, however, experimental validation is vital and demands further investigations. The roles of specific hemodynamic variables, the non-Newtonian behavior of blood and its particulate nature at small scales, the flow disturbances caused by the heart cycle, and the anatomy of certain arteries (i.e., bifurcations and tortuosity of vessels of some regions) in the determination of the dynamic performance of microbots are of paramount importance. This paper presents a critical analysis of the state-of-the-art literature related to pulsatile blood flow around microbots.

Extensional Magnetorheology of Viscoelastic Human Blood Analogues Loaded with Magnetic Particles.

This study represents a pioneering work on the extensional magnetorheological properties of human blood analogue fluids loaded with magnetic microparticles. Dynabeads M-270 particles were dispersed in Newtonian and viscoelastic blood analogue fluids at 5% wt. Capillary breakup experiments were performed, with and without the influence of an external magnetic field aligned with the flow direction. The presence of the particles increased the viscosity of the fluid, and that increment was larger when embedded within a polymeric matrix. The application of an external magnetic field led to an even larger increment of the viscosity of the working fluids, as the formation of small aggregates induced an increment in the effective volume fraction of particles. Regarding the liquid bridge stability, the Newtonian blood analogue fluid remained as a Newtonian liquid exhibiting a pinch-off at the breakup time in any circumstance. However, in the case of the viscoelastic blood analogue fluid, the presence of the particles and the simultaneous application of the magnetic field enhanced the formation of the beads-on-a-string structure, as the Ohnesorge number remained basically unaltered, whereas the time of the experiment increased due to its larger viscosity, which resulted in a decrease in the Deborah Number. This result was confirmed with fluids containing larger concentrations of xanthan gum.

Coronavirus disease 2019, allergic diseases, and allergen immunotherapy: Possible favorable mechanisms of interaction.

Background: Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease. Objective: To review immune changes brought along by each of these entities and how they might interrelate. Methods: We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection. Results: We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation. Conclusion: As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.

Universal influenza vaccination: a Mexican Expert Position Paper.

OBJECTIVE: Influenza is a costly disease for the population. It is a cause of seasonal morbidity and mortality, epidemics and pandemics or syndemics. Given the variability of the virus, surveillance systems are implemented in order to update the strains and include them in the annual influenza vaccine. This vaccine is currently recommended in some high-risk groups. However, universal vaccination remains controversial. To evaluate the evidence and describe the position of a panel of experts on the relevance of universal vaccination against influenza virus. MATERIAL AND METHODS: Five clinical questions were asked, whereby a systematic search of the literature in electronic sources and a Delphi panel were carried out. The evidence was analyzed, and recommendations were issued by the experts. RESULTS: The group of experts recommends vaccinating the population starting at six months of age and include people who live with egg protein allergy, with comorbidities (diabetes, obesity, cancer), health workers and pregnant women. CONCLUSIONS: Vaccination, starting with vulnerable groups, is a necessary, ethical and cost-effective strategy. However, expanding the coverage to achieve universal vaccination could reduce the transmission of the disease and its consequences in the population.

OBJETIVO: La influenza es una enfermedad costosa para la población. Es causa de morbimortalidad estacional, epidemias y pandemias o sindemias. Debido a la variabilidad del virus, se implementan sistemas de vigilancia para actualizar las cepas e incluirlas en la vacuna antiinfluenza anual. Actualmente se recomienda esta vacuna en algunos grupos de alto riesgo. Sin embargo, la vacunación universal es aún controvertida. Evaluar la evidencia y describir la posición de un panel de expertos sobre la pertinencia de la vacunación universal contra el virus de influenza. MATERIAL Y MÉTODOS: Se realizaron cinco preguntas clínicas, con las que se realizó una búsqueda sistemática de la literatura en fuentes electrónicas y un panel Delphi. Se analizó la evidencia y se emitieron recomendaciones por los expertos. RESULTADOS: El grupo de expertos recomienda vacunar a la población desde los seis meses de edad e incluir a personas que viven con alergia a la proteína del huevo, con comorbilidades (diabetes, obesidad, cáncer), trabajadores de la salud y embarazadas. CONCLUSIONES: La vacunación, iniciando con los grupos vulnerables, es una estrategia necesaria, ética y costo-efectiva. Sin embargo, extender la cobertura para lograr la vacunación universal podría disminuir la transmisión de la enfermedad y sus consecuencias en la población.

Rheological characterization of polymeric solutions used in spray drying process.

The present works contributes with a rheological characterization of the most commonly used polymers and solvents to formulate amorphous solid dispersions by means of spray drying process: copovidone, hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS) and a copolymer of methacrylic acid and methyl methacrylate (1:1 ratio and commercially known as Eudragit L100). The organic-based solutions are characterized in terms of surface tension, shear viscosity and relaxation time. HPMC and HPMCAS solutions exhibit shear thinning behaviour, i.e. decrease of shear viscosity with the increasing shear rate imposed, while the samples with Eudragit L100 can be considered Boger fluids, showing a constant viscosity but maintaining its viscoelastic character. Under uniaxial extensional flow, these polymers solutions exhibit a viscoelastic behavior with an increasing relaxation time with an increasing concentration, and in some cases showed a 'beads-on-string' effect. In contrast, copovidone showed a Newtonian fluid behavior, with the absence of elasticity. The fundamental understanding and characterization of the present work may be further applied to atomization modelling and support and expedite spray drying process development.

Critical overlap concentration and intrinsic viscosity data of xanthan gum aqueous solutions in dimethyl sulfoxide.

This is the supplementary information of the research paper "Haemodynamics around confined microscopic cylinders" by Rodrigues et al. [1]. The critical overlap concentration of entanglement of polymer coils indicates whether a polymer solution is dilute or semidilute. Here, the reader will find the determination of c * for xanthan gum aqueous solutions in 52 wt.% of dimethyl sulfoxide, often used as non-particulate blood analogues. From the shear flow curves of a dilution series of the polymer the zero-shear viscosities η 0 were obtained, allowing us to estimate the intrinsic viscosity [ η ] based on the xanthan gum concentration of the fluids. Two methodologies for doing so are described: using information from multi-concentration measurements and from a single polymer solution (rough estimate). With the intrinsic viscosity the determination of c * is straightforward.

Breakup of an electrified viscoelastic liquid bridge.

We study both numerically and experimentally the breakup of a viscoelastic liquid bridge formed between two parallel electrodes. The polymer solutions and applied voltages are those commonly used in electrospinning and near-field electrospinning. We solve the leaky-dielectric finitely extensible nonlinear elastic-Peterlin (FENE-P) model to describe the dynamical response of the liquid bridge under isothermal conditions. The results show that the surface charge screens the inner electric field perpendicular to the free surface over the entire dynamical process. The liquid bridge deformation produces a normal electric field on the outer side of the free surface that is commensurate with the axial one. The surface conduction does not significantly affect the current intensity in the time interval analyzed in the experiments. The force due to the shear electric stress becomes comparable to both the viscoelastic and surface tension forces in the last stage of the filament. However, it does not alter the elastocapillary balance in the filament. As a consequence, the extensional relaxation times measured from the filament exponential thinning approximately coincides with the stress relaxation time prescribed in the FENE-P model. The above results allow us to interpret correctly the experiments. In the experiments, we measure the filament electrical conductivity and extensional relaxation time for polyethylene oxide (PEO) dissolved in deionized water and in a mixture of water and glycerine. We compare the filament electrical conductivity with the value measured in hydrostatic conditions for the same estimated temperature. Good agreement was found for PEO dissolved in water + glycerine, which indicates that the change in the filament microscopic structure due to the presence of stretched polymeric chains does not significantly alter the ion mobility in the stretching direction. Significant deviations are found for PEO dissolved in deionized water. These deviations may be attributed to the heat transferred to the ambient, which is neglected in the calculation of the filament temperature. We measure the extensional relaxation time from the images acquired during the filament thinning. The relaxation times obtained in the first stage of the exponential thinning hardly depend on the applied voltage. Little but measurable influence of the applied voltage is found in the last phase of the filament thinning.

Direct Ink Writing Glass: A Preliminary Step for Optical Application.

In this paper, we present a preliminary study and conceptual idea concerning 3D printing water-sensitive glass, using a borosilicate glass with high alkali and alkaline oxide contents as an example in direct ink writing. The investigated material was prepared in the form of a glass frit, which was further ground in order to obtain a fine powder of desired particle size distribution. In a following step, inks were prepared by mixing the fine glass powder with Pluoronic F-127 hydrogel. The acquired pastes were rheologically characterized and printed using a Robocasting device. Differential scanning calorimetry (DSC) experiments were performed for base materials and the obtained green bodies. After sintering, scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses were carried out in order to examine microstructure and the eventual presence of crystalline phase inclusions. The results confirmed that the as obtained inks exhibit stable rheological properties despite the propensity of glass to undergo hydrolysis and could be adjusted to desirable values for 3D printing. No additional phase was observed, supporting the suitability of the designed technology for the production of water sensitive glass inks. SEM micrographs of the sintered samples revealed the presence of closed porosity, which may be the main reason of light scattering.

Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

Microfluidics as a Platform for the Analysis of 3D Printing Problems.

Fused Filament Fabrication is an extrusion deposition technique in which a thermoplastic filament is melted, pushed through a nozzle and deposited to build, layer-by-layer, custom 3D geometries. Despite being one of the most widely used techniques in 3D printing, there are still some challenges to be addressed. One of them is the accurate control of the extrusion flow. It has been shown that this is affected by a reflux upstream the nozzle. Numerical models have been proposed for the explanation of this back-flow. However, it is not possible to have optical access to the melting chamber in order to confirm the actual behavior of this annular meniscus. Thus, microfluidics seems to be an excellent platform to tackle this fluid flow problem. In this work, a microfluidic device mimicking the 3D printing nozzle was developed, to study the complex fluid-flow behavior inside it. The principal aim was to investigate the presence of the mentioned back-flow upstream the nozzle contraction. As the microfluidic chip was fabricated by means of soft-lithography, the use of polymer melts was restricted due to technical issues. Thus, the working fluids consisted of two aqueous polymer solutions that allowed replicating the printing flow conditions in terms of Elasticity number and to develop a D e - R e flow map. The results demonstrate that the presence of upstream vortices, due to the elasticity of the fluid, is responsible for the back-flow problem.

Towards an Optimal Pressure Tap Design for Fluid-Flow Characterisation at Microscales.

Measuring fluid pressure in microchannels is difficult and constitutes a challenge to even the most experienced of experimentalists. Currently, to the best of the authors' knowledge, no optimal solution are being used for the design of pressure taps, nor guidelines concerning their shape and its relation with the accuracy of the readings. In an attempt to address this issue, a parametric study was devised to evaluate the performance of different pressure tap designs, 18 in total. These were obtained by combining three shape parameters: sub-channel width (w) and sub-channel-tap radius (R) or angle (α), while having the sub-channel length kept constant. For each configuration, pressure drop measurements were carried out along several lengths of a straight microfluidic rectangular channel and later compared to an analytical solution. The microchannels were fabricated out of PDMS using standard soft-lithography techniques, pressure drop was measured with differential pressure sensors, the test fluid was DI water and the flow conditions varied from creeping flow up to R e c ∼100. Pressure taps, having smooth contours (characterised by the radius R) and a sub-channel width (w) of 108 µ m , performed the best with results from that of radius R = 50 µ m only falling short of the theory by a mere ∼ 5 % .

Choline Rescues Behavioural Deficits in a Mouse Model of Rett Syndrome by Modulating Neuronal Plasticity.

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Choline, a dietary micronutrient found in most foods, has been shown to be important for brain development and function. However, the exact effects and mechanisms are still unknown. We found that 13 mg/day (1.7 × required daily intake) of postnatal choline treatment to Mecp2-conditional knockout mice rescued not only deficits in motor coordination, but also their anxiety-like behaviour and reduced social preference. Cortical neurons in the brains of Mecp2-conditional knockout mice supplemented with choline showed enhanced neuronal morphology and increased density of dendritic spines. Modelling RTT in vitro by knocking down the expression of the MeCP2 protein with shRNA, we found that choline supplementation to MeCP2-knockdown neurons increased their soma sizes and the complexity of their dendritic arbors. Rescue of the morphological defects could lead to enhanced neurotransmission, as suggested by an observed trend of increased expression of synaptic proteins and restored miniature excitatory postsynaptic current frequency in choline-supplemented MeCP2-knockdown neurons. Through the use of specific inhibitors targeting each of the known physiological pathways of choline, synthesis of phosphatidylcholine from choline was found to be essential in bringing about the changes seen in the choline-supplemented MeCP2-knockdown neurons. Taken together, these data reveal a role of choline in modulating neuronal plasticity, possibly leading to behavioural changes, and hence, a potential for using choline to treat RTT.

Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature.

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative.

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication.

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Multifocal Recurrent Osteomyelitis and Hemophagocytic Lymphohistiocytosis in a Boy with Partial Dominant IFN-γR1 Deficiency: Case Report and Review of the Literature.

Mutations in the genes coding for cytokines, receptors, second messengers, and transcription factors of interferon gamma (IFN-γ) immunity cause Mendelian susceptibility to mycobacterial disease (MSMD). We report the case of a 7-year-old male patient with partial dominant (PD) IFN-γ receptor 1 deficiency who had suffered from multifocal osteomyelitis attributable to bacille Calmette-Guérin vaccination since the age of 18 months. He developed hemophagocytic lymphohistiocytosis (HLH), a hyper-inflammatory complication, and died with multiorgan dysfunction, despite having been diagnosed and treated relatively early. Patients with PD IFN-γR1 deficiency usually have good prognosis and might respond to human recombinant subcutaneous IFN-γ. Several monogenic congenital defects have been linked to HLH, a catastrophic "cytokine storm" that is usually ascribed to lymphocyte dysfunction and thought to be triggered by interferon gamma. This is the sixth patient with both MSMD and HLH of whom we are aware. The fact that patients with macrophages that cannot respond to IFN-γ still develop HLH, bring these assumptions into question.

Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome.

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for approximately 95 % of all RTT cases. To model RTT in vitro, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of two RTT patients with different mutations (MECP2 (R306C) and MECP2 (1155Δ32)) in their MECP2 gene. We found that these iPSCs were capable of differentiating into functional neurons. Compared to control neurons, the RTT iPSC-derived cells had reduced soma size and a decreased amount of synaptic input, evident both as fewer Synapsin 1-positive puncta and a lower frequency of spontaneous excitatory postsynaptic currents. Supplementation of the culture media with choline rescued all of these defects. Choline supplementation may act through changes in the expression of choline acetyltransferase, an important enzyme in cholinergic signaling, and also through alterations in the lipid metabolite profiles of the RTT neurons. Our study elucidates the possible mechanistic pathways for the effect of choline on human RTT cell models, thereby illustrating the potential for using choline as a nutraceutical to treat RTT.

Impact of long-term use of oral nutritional supplement on nutritional adequacy, dietary diversity, food intake and growth of Filipino preschool children.

Nutrient deficiencies during childhood have adverse effects on child growth and health. In a single-arm 48-week long-term intervention, we previously reported the efficacy of oral nutritional supplementation (ONS) and dietary counselling on catch-up growth and growth maintenance in nutritionally at-risk Filipino children. The present analysis was done to assess the contributing effects of ONS to nutritional adequacy, dietary diversity, food intake and longitudinal growth. ONS (450 ml) was consumed daily providing 450 kcal (1880 kJ) and at least 50 % of micronutrient requirements among 200 children aged 3-4 years with weight-for-height percentiles between 5th and 25th (WHO Growth Standards). Weight, height and dietary intakes using 24-h food recalls were measured at baseline, and at weeks 4, 8, 16, 24, 32, 40 and 48. Nutrient adequacy and dietary diversity score (DDS) were calculated. Generalised estimating equations were used to assess the effects of total nutrient intakes, DDS, ONS compliance and sociodemographic factors on longitudinal growth. The percentages of children with adequate intake of energy, protein, Fe, Ca and some vitamins at each post-baseline visit were improved from baseline, reaching 100 % for most nutrients. DDS was also increased from baseline and reached significance from week 16 onwards (P < 0·01). Male children, total energy intake and parental employment status were associated with weight-for-height percentile gain (P < 0·05), whereas higher parental education level and ONS compliance were significantly associated with height-for-age percentile gain over time (P < 0·05). Long-term ONS intervention did not interfere with normal food intake and helped promote nutritional adequacy and growth of Filipino children.