Early Life Microbiota Colonization at Six Months of Age: A Transitional Time Point

Background: Early life gut microbiota is involved in several biological processes, particularly metabolism, immunity, and cognitive neurodevelopment. Perturbation in the infant's gut microbiota increases the risk for diseases in early and later life, highlighting the importance of understanding the connections between perinatal factors with early life microbial composition. The present research paper is aimed at exploring the prenatal and postnatal factors influencing the infant gut microbiota composition at six months of age. Methods: Gut microbiota of infants enrolled in the longitudinal, prospective, observational study "A.MA.MI" (Alimentazione MAmma e bambino nei primi MIlle giorni) was analyzed. We collected and analyzed 61 fecal samples at baseline (meconium, T0); at six months of age (T2), we collected and analyzed 53 fecal samples. Samples were grouped based on maternal and gestational weight factors, type of delivery, type of feeding, time of weaning, and presence/absence of older siblings. Alpha and beta diversities were evaluated to describe microbiota composition. Multivariate analyses were performed to understand the impact of the aforementioned factors on the infant's microbiota composition at six months of age. Results: Different clustering hypotheses have been tested to evaluate the impact of known metadata factors on the infant microbiota. Neither maternal body mass index nor gestational weight gain was able to determine significant differences in infant microbiota composition six months of age. Concerning the type of feeding, we observed a low alpha diversity in exclusive breastfed infants; conversely, non-exclusively breastfed infants reported an overgrowth of Ruminococcaceae and Flavonifractor. Furthermore, we did not find any statistically significant difference resulting from an early introduction of solid foods (before 4 months of age). Lastly, our sample showed a higher abundance of clostridial patterns in firstborn babies when compared to infants with older siblings in the family. Conclusion: Our findings showed that, at this stage of life, there is not a single factor able to affect in a distinct way the infants' gut microbiota development. Rather, there seems to be a complex multifactorial interaction between maternal and neonatal factors determining a unique microbial niche in the gastrointestinal tract

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

<p>Abstract</p> <p>Background</p> <p>Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.</p> <p>Discussion</p> <p>In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.</p> <p>As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.</p> <p>Summary</p> <p>Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.</p

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19

Changes in circulating levels of adiponectin and leptin in children during the first two years of life

Aim. Adiponectin, leptin and insulin play an important role in the control of growth and glyco-metabolic homeostasis both during pre-and post-natal life. In order to find out markers indicative of post-natal growth, we evaluated circulating levels of these growth factors in full term small for gestational age (SGA) children, during the first 2 years of life, correlating them with the auxological parameters. Methods. Fourteen SGA (8 males and 6 females) and 16 AGA (appropriate for gestional age) infants (7 males and 9 females) have been included in this study, recording length, weight, body mass index (BMI), adiponectin, leptin and insulin levels at birth. In SGA subjects, these biochemical and clinical parameters have also been evaluated at the first and at the second year of age. Results. AGA and SGA adiponectin and insulin levels at birth did not show statistically significant differences, while leptin concentrations were significantly (P=0.011) lower in SGA children (median 418.49, range 157.68-903.67 pg/mL) in comparison with AGA ones (median 811.71, range 312.50-3085.95 pg/mL). Conclusion. In conclusion, at birth adiponectin and insulin levels do not differ between AGA and SGA subjects while leptin concentrations are significantly lower in SGA infants and positively correlated to the birthweight

Control of hepatitis B: evaluation of two different vaccinal schedules in newborns from HBsAg negative mothers

504 healthy infants, born to HBsAg negative mothers from May 1st to December 31st 1991, were randomly allocated to an accelerated (group A9 or traditional (group B) immunization schedule. The group A infants were immunized at 4 days, 1 moth and 3 months of life with 10 micrograms of recombinant HBV vaccine (Engerix B, SKF) while the group B infants were immunized at 4 days, 1 month and 6 months of life with the same dose of vaccine. One month after the first dose of vaccine, 9.2% of the infants in both groups had and HBsAb serum level > 10mlU/ml. One month after the booster dose, at 4 months of life for group A and at 7 months for group B, 97.40% and 98.53% of the infants presented a serum level > 10 mlU/ml respectively. None in group A and only 2 patients in group B could be considerred non-responders (serum concentration below 2 mlU/ml) and 4 infants in group A and 4 in group B were considered hypo-responders (serum level between 2.1 and 9.9 mlU/ml). Immunogenetic study performed on the 2 non-responders and 6 of the hypo-responders, revealed the presence in all but two of the HLA haplotypes, classifically involved in the lack of hyporesponsiveness to foreign peptides namely: HLA-DR7; DQ2, DR4; DQ3, Dr15; DQ6 and DR3; DQ2. Surprisingly, 2 hypo-responders carried the HLA haplotypes (DR11, DQ7 and DR13, DQ6), usually associated with hyperresponsiveness. Both vaccinal cycles provided evidence that infants respond well to vaccination, started at birth, against hepatitis B virus with a high degree of protection