Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review

BACKGROUND: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. OBJECTIVE: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. METHODS: Electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. RESULTS: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitisation; 9, wheezing/asthma; 6, food allergy; 3, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. CONCLUSION AND CLINICAL RELEVANCE: In contrast with previous findings we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardised methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required

Excessive weight gain followed by catch-down in exclusively breastfed infants: An exploratory study

Some infants experience excessive weight gain (EWG) during exclusive breastfeeding, but causes and consequences are unknown. The objective was to identify factors associated with early EWG. Infants with EWG (HW-group) were examined at 5, 9 and 18 mo and compared to a breastfed group with normal weight gain (NW-group). Anthropometry, body composition, milk and blood samples, and milk intake were measured. Mean body-mass-index-for-age z-scores (BAZ) increased 1.93 from birth to 5 mo in the HW-group (n = 13) while the NW-group (n = 17) was unchanged (−0.01). The HW-group had 70% more fat mass at 5 mo, and then showed marked catch-down in BAZ from 5 to 18 mo (−0.84). Milk intake at 5–6 mo did not differ between the groups. In the HW-group milk-leptin was lower at 5 mo and serum-leptin was considerably higher at 5 and 9 mo compared to the NW-group. Serum-leptin at 5 mo was positively associated with weight-for-age z-score (WAZ) and fat mass and negatively with WAZ change from 5 to 9 mo. In conclusion, breastfed infants with EWG had catch-down growth when other foods were introduced. Low milk-leptin in the HW-group may have stimulated appetite and milk intake when weight gain was high. High serum-leptin in the HW-group suggests early leptin resistance, which could impact cerebral regulation of energy intake. Larger studies are needed to confirm these results

An active electrode for biopotential recording from small localized bio-sources

BACKGROUND: Laser bio-stimulation is a well-established procedure in Medical Acupuncture. Nevertheless there is still a confusion as to whether it works or the effect is just placebo. Although a plethora of scientific papers published, showing positive clinical results, there is still a lack of objective scientific proofs about the bio-stimulation effect of lasers used in Acupuncture. The objective of this work was to design and build a body surface electrode and an amplifier for biopotential recording from acupuncture points, considered here as small localized bio-sources (SLB). The design is aimed for studying SLB potentials provoked by laser stimulus, in search for objective proofs of the bio-stimulation effect of lasers used in Medical Acupuncture. METHODS: The active electrode presented features a new adjustable anchoring system and fractionation of the biopotential amplifier between the electrode and the cabinet's location. The new adjustable electrode anchoring system is designed to reduce the electrode-skin contact impedance, its variation and motion artifacts. That is achieved by increasing the electrode-skin tension and decreasing its relative movement. Additionally the sensing element provides local constant skin stretching thus eliminating the contribution of the skin potential artifact. The electrode is attached to the skin by a double-sided adhesive pad, where the sensing element is a stainless steel, 4 mm in diameter. The fractionation of the biopotential amplifier is done by incorporating the amplifier's front-end op-amps at the electrodes, thus avoiding the use of extra buffers. The biopotential amplifier features two selectable modes of operation: semi-AC-mode with a -3 dB bandwidth of 0.32–1000 Hz and AC-mode with a bandwidth of 0.16–1000 Hz. RESULTS: The average measured DC electrode-skin contact impedance of the proposed electrode was 450 kΩ, with electrode tension of 0.3 kg/cm(2 )on an unprepared skin of the inner forearm. The peak-to-peak noise voltage measured at the amplifier output, with input terminals connected to common, was 10 mV(p-p), or 2 μV(p-p )referred to the input. The common-mode rejection ratio of the amplifier was 96 dB at 50 Hz, measured with imbalanced electrodes' impedances. The prototype was also tested practically and sample records were obtained after a low intensity SLB laser stimulation. All measurements showed almost a complete absence of 50 Hz interference, although no electrolyte gel or skin preparation was applied. CONCLUSION: The results showed that the new active electrode presented significantly reduced the electrode-skin impedance, its variation and motion artifact influences. This allowed SLB signals with relatively high quality to be recorded without skin preparation. The design offers low noise and major reduction in parts, size and power consumption. The active electrode specifications were found to be better or at least comparable to those of other existing designs

Avaliação das técnicas de massagem e ordenha no tratamento do ingurgitamento mamário por termografia

OBJETIVO: evaluar los métodos de masaje y bombeo en el tratamiento de la congestión mamaria posparto a través de la termografía. MÉTODO: el estudio se realizó en el Banco de Leche Humana de un hospital en Curitiba, Brasil. Se seleccionaron al azar 16 mujeres en periodo de lactancia con congestión con clasificación lobar, ampular y glandular, moderada e intensa. Se compararon los patrones diferenciales de temperatura, antes y después del tratamiento por medio de masaje y bombeo. RESULTADOS: se encontró un degradado negativo de 0,3°C de temperatura entre el pre y post-tratamiento en el grupo experimental. Las mamas con intensa congestión eran 0,7°C más caliente en comparación a aquellos con congestión moderada. CONCLUSIÓN: el masaje y el bombeo electromecánico fueron superiores a los métodos manuales cuando se evaluaron por termografía. REBEC: U1111-1136-9027.OBJETIVO: avaliar técnicas de massagem e ordenha no tratamento do ingurgitamento mamário puerperal, por meio da termografia. MÉTODO: a pesquisa foi realizada no Banco de Leite Humano de um hospital de Curitiba, Brasil. Selecionaram-se, aleatoriamente, 16 lactantes com ingurgitamento com classificação lobar, ampolar e glandular moderado e intenso. Compararam-se os padrões diferenciais de temperatura, antes e após o tratamento realizado, por meio de massagem e ordenha. RESULTADOS: constatou-se um gradiente negativo de 0,3ºC de temperatura entre o pré e o pós-tratamento no grupo experimental. Mamas com ingurgitamento intenso foram 0,7ºC mais quentes quando comparadas com ingurgitamento moderado. CONCLUSÃO: a massagem e ordenha eletromecânicas são superiores às manuais, quando avaliadas por termografia. REBEC: U1111-1136-9027.OBJECTIVE: to evaluate techniques of massage and pumping in the treatment of postpartum breast engorgement through thermography. METHOD: the study was conducted in the Human Milk Bank of a hospital in Curitiba, Brazil. We randomly selected 16 lactating women with engorgement with the classification lobar, ampullary and glandular, moderate and intense. We compared the differential patterns of temperature, before and after the treatment by means of massage and pumping. RESULTS: we found a negative gradient of 0.3°C of temperature between the pre- and post-treatment in the experimental group. Breasts with intense engorgement were 0.7°C warmer when compared with moderate engorgement. CONCLUSION: massage and electromechanical pumping were superior to manual methods when evaluated by thermography. REBEC: U1111-1136-9027

Duloxetine compared with fluoxetine and venlafaxine: use of meta-regression analysis for indirect comparisons

BACKGROUND: Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with venlafaxine, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that duloxetine should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a systematic review of the efficacy of duloxetine, fluoxetine and venlafaxine versus placebo in the treatment of Major Depressive Disorder (MDD), and performed indirect comparisons through meta-regressions. METHODS: The bibliography of the Agency for Health Care Policy and Research and the CENTRAL, Medline, and Embase databases were interrogated using advanced search strategies based on a combination of text and index terms. The search focused on randomized placebo-controlled clinical trials involving adult patients treated for acute phase Major Depressive Disorder. All outcomes were derived to take account for varying placebo responses throughout studies. Primary outcome was treatment efficacy as measured by Hedge's g effect size. Secondary outcomes were response and dropout rates as measured by log odds ratios. Meta-regressions were run to indirectly compare the drugs. Sensitivity analysis, assessing the influence of individual studies over the results, and the influence of patients' characteristics were run. RESULTS: 22 studies involving fluoxetine, 9 involving duloxetine and 8 involving venlafaxine were selected. Using indirect comparison methodology, estimated effect sizes for efficacy compared with duloxetine were 0.11 [-0.14;0.36] for fluoxetine and 0.22 [0.06;0.38] for venlafaxine. Response log odds ratios were -0.21 [-0.44;0.03], 0.70 [0.26;1.14]. Dropout log odds ratios were -0.02 [-0.33;0.29], 0.21 [-0.13;0.55]. Sensitivity analyses showed that results were consistent. CONCLUSION: Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine. Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate. In the absence of relevant data from head-to-head comparison trials, results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine

Immune Evasion by Yersinia enterocolitica: Differential Targeting of Dendritic Cell Subpopulations In Vivo

CD4+ T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an experimental mouse infection model. We found that OVA-specific CD4+ T cells had a reduced potential to proliferate when stimulated with OVA after infection with Ye compared to control mice. Additionally, proliferation of OVA-specific CD4+ T cells was markedly reduced when cultured with splenic CD8α+ DCs from Ye infected mice in the presence of OVA. In contrast, T-cell proliferation was not impaired in cultures with CD4+ or CD4−CD8α− DCs isolated from Ye infected mice. However, OVA uptake and degradation as well as cytokine production were impaired in CD8α+ DCs, but not in CD4+ and CD4−CD8α− DCs after Ye infection. Pathogenicity factors (Yops) from Ye were most frequently injected into CD8α+ DCs, resulting in less MHC class II and CD86 expression than on non-injected CD8α+ DCs. Three days post infection with Ye the number of splenic CD8α+ and CD4+ DCs was reduced by 50% and 90%, respectively. The decreased number of DC subsets, which was dependent on TLR4 and TRIF signaling, was the result of a faster proliferation and suppressed de novo DC generation. Together, we show that Ye infection negatively regulates the stimulatory capacity of some but not all splenic DC subpopulations in vivo. This leads to differential antigen uptake and degradation, cytokine production, cell loss, and cell death rates in various DC subpopulations. The data suggest that these effects might be caused directly by injection of Yops into DCs and indirectly by affecting the homeostasis of CD4+ and CD8α+ DCs. These events may contribute to reduced T-cell proliferation and immune evasion of Ye