Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

Sustained Energy Deficit Following Perinatal Asphyxia: A Shift towards the Fructose-2,6-bisphosphatase (TIGAR)-Dependent Pentose Phosphate Pathway and Postnatal Development

Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia (PA). PA causes an energy failure, leading to cell dysfunction and death if re-oxygenation is not promptly restored. PA is associated with long-term effects, challenging the ability of the brain to cope with stressors occurring along with life. We review here relevant targets responsible for metabolic cascades linked to neurodevelopmental impairments, that we have identified with a model of global PA in rats. Severe PA induces a sustained effect on redox homeostasis, increasing oxidative stress, decreasing metabolic and tissue antioxidant capacity in vulnerable brain regions, which remains weeks after the insult. Catalase activity is decreased in mesencephalon and hippocampus from PA-exposed (AS), compared to control neonates (CS), in parallel with increased cleaved caspase-3 levels, associated with decreased glutathione reductase and glutathione peroxidase activity, a shift towards the TIGAR-dependent pentose phosphate pathway, and delayed calpain-dependent cell death. The brain damage continues long after the re-oxygenation period, extending for weeks after PA, affecting neurons and glial cells, including myelination in grey and white matter. The resulting vulnerability was investigated with organotypic cultures built from AS and CS rat newborns, showing that substantia nigra TH-dopamine-positive cells from AS were more vulnerable to 1 mM of H2O2 than those from CS animals. Several therapeutic strategies are discussed, including hypothermia; N-acetylcysteine; memantine; nicotinamide, and intranasally administered mesenchymal stem cell secretomes, promising clinical translation.

Effect on the reduction of bacterial load after surgical hand antisepsis with triclosan 0.5% compared to triclosan 0.5% followed by 70% alcoholic solution

Triclosan 0.5% by scrubbing does not meet the UNE-EN12791 criteria to be used in the surgical hand preparation (SHP). Triclosan 0.5% by scrubbing followed by ethanol 70% hand rubbing is suitable without the additional characteristic of sustained effect. This limited effectiveness implies that triclosan should be avoided in SHP given the restrictions on its use in consumer antiseptic products. The trial was registered at ClinicalTrials.gov (ID: NCT04538365).

Thirty-year effects of liming on soil and foliage chemistry and growth of northern hardwoods in Pennsylvania, USA

The longevity of a single 22.4 Mg ha^-1 application of dolomitic limestone at four northern hardwood stands was evaluated over thirty years (1986-2016) to determine whether changes in soils, foliage, and tree growth were sustained on the unglaciated Allegheny Plateau in northern Pennsylvania, USA. In limed plots, soils, sampled to 45-55 cm depth, and sugar maple (<i>Acer saccharum</i> Marsh.) and black cherry (<i>Prunus serotina</i> Ehrh.) foliage had significantly ( P ≤ 0.05) greater concentrations of calcium (Ca) and magnesium (Mg) through 2016 compared with samples from unlimed plots. Calcium and Mg capitals (g m^-2) in the Oi through A horizon combined were greater on limed plots than unlimed plots, largely due to increases in the thickness and nutrient concentration in the A horizon. Over 30-years, sugar maple basal area increment (cm² yr^-1 BAINC) ) was greater in limed plots, American beech (<i>Fagus grandifolia</i> Ehrh.) BAINC was unaffected, and black cherry BAINC was reduced in limed plots compared with unlimed plots. The sustained effect of this one-time lime treatment shows the strong role of efficient nutrient cycling in forests and suggests that the benefits over a substantial portion of a stand rotation may increase the feasibility of operational liming.

Case Study on Moolakabeejadi Lepa in Dadru Kushta

In recent years; there has been a considerable increase in the incidence of skin problems in the developing countries like India and tropical countries due to less immunity, unhygienic, living conditions, and nutrition. The most exposed part of the body is skin. In cosmetic point of view patient who suffers with any skin diseases leads to experience physical, emotional and socio-economic embarrassment in his/her society because mirror that reflects internal & external pathology in such diseases is skin which helps in diagnosis. In among the various skin infections tinea/ringworm is one which is spreading rapidly and affecting all the age group of population. Skin infection is termed as Twak Vikara or Kushta roga in Ayurveda. In among the Kushta Roga, Dadru termed as a Dadru Kushta. In contemporary medicine, tinea/ringworm which is skin fungal infection is correlated to Dadru Kushta due to similarities in their signs and symptoms. Large community prevalence studies have demonstrated that between 20-30% of the population have various skin problems requiring attention. Present study was conducted on diagnosed patients of Dadru Kushta in patients Moolakabeejadi Lepa was applied. The drugs used in the formulations having Kandughana, Kushtahara, Krimighna, Shodhana and Tridoshahara in their properties. The results revealed highly significant effect of Moolakabeejadi Lepa in various subjective and objective parameters like Raga, Kandu and number of Pidika, number of Mandala after treatment. During follow up period of 15 days the drug effect suggested the sustained effect on the disease.

Impact of childhood and maternal vaccination against diphtheria, tetanus, and pertussis in Colombia

Background: In Latin America, there are few studies of the impact of vaccination against diphtheria, tetanus, and pertussis. We estimate the impact of infant and maternal vaccination on the incidence of these diseases in Colombia.Design and methods: an interrupted time series study analyzing the incidence before and after of vaccination with DwPT (1975-2018) and with Tdap in pregnant women (2008-2018). A segmented regression model with negative binomial distribution estimated the change in level and trend of the predicted incidence ratio after vaccination in relation to the incidence if vaccination had not been started (IRR), using a Prais Winsten regression.Results: The pertussis IRR decreased immediately after the start of childhood vaccination (0.91, p=0.51), but this was only significant (1.01, p<0.001) along with the trend per year, after the start of maternal vaccination (0.98, p<0.001). In the absence of vaccination, the incidence would not have been reduced. Neonatal tetanus had the highest rate of change with significant reduction -1.69 - CI 95%: -2.91, -0.48). The trend after vaccination was the highest with an annual reduction of 19% (0.81, p=0.001). The change in incidence of diphtheria was significant, although slow (-0.02 - CI 95%: -0.04, -0.004). The sustained effect in the post-vaccination period was smaller (0.95, p=0.79).Conclusions: Childhood and maternal vaccination markedly reduced the incidence of pertussis and neonatal tetanus. It is necessary to maintain optimal vaccination coverage and surveillance, within an integrated elimination plan, which prevents the resurgence of these diseases.

Life-threatening diarrhea in neuroendocrine tumors: two case reports

Background Neuroendocrine tumors are rare, heterogeneous neoplasms that produce a wide variety of clinical symptoms. Diarrhea in neuroendocrine tumors is incredibly common and is usually benign in nature. We report two extreme cases of diarrhea in metastatic neuroendocrine tumors that threatened fatality and provide evidence for steroids as a novel agent in the management of vasoactive intestinal peptide tumors. Case presentation A 63-year-old Caucasian male with a grade 2 (Ki-67 17%) metastatic small bowel neuroendocrine tumor, and a 43-year-old female with a grade 2 (Ki-67 5%) metastatic pancreatic vasoactive intestinal peptide tumor. Both patients suffered life-threatening diarrhea despite extensive treatment modalities, including new systemic agents. This case explains how a lack of compliance and patient under-reporting of symptoms contributed to their challenging clinical course. Only steroids had a significant sustained effect on the diarrhea of the patient with vasoactive intestinal peptide tumor. Conclusions This report discusses two rare cases of life-threatening diarrhea in neuroendocrine tumors and stresses the importance of accurate clinical history taking, patient education, and compliance for symptom control. The report suggests steroids as a potential novel pharmaceutical option in the management of vasoactive intestinal peptide tumors; this is of great significance as it may provide a new approach to their management and potentially act as a life-saving agent in other oncology patients.

Daily Administered Dual-Light Photodynamic Therapy Provides a Sustained Antibacterial Effect on Staphylococcus aureus

New means to reduce excessive antibiotic use are urgently needed. This study tested dual-light aPDT against Staphylococcus aureus biofilm with different relative ratios of light energy with indocyanine green. We applied single-light aPDT (810 nm aPDT, 405 aBL) or dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL), in both cases, together with the ICG photosensitizer with constant energy of 100 or 200 J/cm2. Single-dose light exposures were given after one-day, three-day, or six-day biofilm incubations. A repeated daily dose of identical light energy was applied during biofilm incubations for the three- and six-day biofilms. Using 100 J/cm2 light energy against the one-day biofilm, the dual-light aPDT consisting of more than half of aBL was the most effective. On a three-day maturated biofilm, single-dose exposure to aPDT or dual-light aPDT was more effective than aBL alone. With total light energy of 200 J/cm2, all dual-light treatments were effective. Dual-light aPDT improves the bactericidal effect on Staphylococcus aureus biofilm compared to aPDT or aBL and provides a sustained effect. An increase in the relative ratio of aBL strengthens the antibacterial effect, mainly when the treatment is repeatedly applied. Thus, the light components’ energy ratio is essential with dual-light.

Signaling Pathways in Proton and Non-proton ASIC1a Activation

Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases as well as pain conditions. Classically, ASICs are described as transiently activated by a reduced pH, followed by desensitization; the activation allows sodium influx, and in the case of ASIC1a-composed channels, also calcium to some degree. Several factors are emerging and extensively analyzed as modulators, activating, inhibiting, and potentiating specific channel subunits. However, the signaling pathways triggered by channel activation are only starting to be revealed.The channel has been recently shown to be activated through a mechanism other than proton-mediated. Indeed, the large extracellular loop of these channels opens the possibility that other non-proton ligands might exist. One such molecule discovered was a toxin present in the Texas coral snake venom. The finding was associated with the activation of the channel at neutral pH via the toxin and causing intense and unremitting pain.By using different pharmacological tools, we analyzed the downstream signaling pathway triggered either by the proton and non-proton activation for human, mouse, and rat ASIC1a-composed channels in in vitro models. We show that for all species analyzed, the non-protonic mode of activation determines the activation of the ERK signaling cascade at a higher level and duration compared to the proton mode.This study adds to the growing evidence of the important role ASIC1a channels play in different physiological and pathological conditions and also hints at a possible pathological mechanism for a sustained effect.

Tips for Effective Implementation of Virtual Reality Exposure Therapy in Phobias—A Systematic Review

Background: The high incidence of phobias and the limited accessibility of psychotherapy are the reasons for the search for alternative treatments that increase the availability of effective treatment. The use of virtual reality (VR) technology is an option with the potential to overcome the barriers in obtaining an effective treatment. VR exposure therapy (VRET) is based on a very similar rationale for in vivo exposure therapy. The study aimed to answer the question of how to perform exposure therapy in a virtual reality environment so that it is effective.Methods: A systematic review of the literature, using PRISMA guidelines, was performed. After analysis of 362 records, 11 research papers on agoraphobia, 28 papers on social phobia and 10 about specific phobias were selected for this review.Results: VRET in agoraphobia and social phobia is effective when performed from 8 to 12 sessions, on average once a week for at least 15 min. In turn, the treatment of specific phobias is effective even in the form of one longer session, lasting 45–180 min. Head mounted displays are an effective technology for VRET. Increasing the frequency of sessions and adding drug therapy may shorten the overall treatment duration. The effectiveness of VRET in phobias is greater without concomitant psychiatric comorbidity and on the condition of inducing and maintaining in the patient an experience of immersion in the VR environment. Long-term studies show a sustained effect of VRET in the treatment of phobias.Conclusion: A large number of studies on in VR exposure therapy in phobias allows for the formulation of some recommendations on how to perform VRET, enabling the effective treatment. The review also indicates the directions of further VRET research in the treatment of phobias.