Impact of Zinc Supplementation on Subsequent Morbidity and Growth in Bangladeshi Children With Persistent Diarrhoea

This study was conducted to explore whether supplementation of zinc to children during persistent diarrhoea has any subsequent effect on morbidity and growth. A prospective follow-up study was conducted among children, aged 3–24 months, with persistent diarrhoea, who participated earlier in a double-blind randomized placebo-controlled trial. During persistent diarrhoea, children were randomly allocated to receive either zinc in multivitamin syrup or only multivitamin syrup for two weeks. After recovering from diarrhoea, 76 children in the multi-vitamin syrup and 78 children in the zinc plus multivitamin syrup group were followed up for subsequent morbidity and growth. Weekly morbidity and two-weekly anthropometric data were collected for the subsequent 12 weeks. Data showed that episodes and duration of diarrhoea were reduced by 38% and 44% respectively with supplementation of zinc. There was no significant difference in the incidence or duration of respiratory tract infection between the zinc-supplemented and the non-supplemented group. Improved linear growth was observed in underweight children (weight-for-age <70% of the National Center for Health Statistics standard) who received zinc compared to those who did not receive

Preferential magma extraction from K-and metal-enriched source regions in the crust

Abstract We compare melting of potassic alteration zones in metamorphosed gold deposits with that of unaltered rocks of the same protolith to examine their relative contributions to crust-derived magmas and to investigate the implications for ore genesis. Potassic hydrothermal alteration, at the crustal levels where orogenic gold deposits form, stabilizes a higher proportion of muscovite and biotite than is possible in unaltered rocks at high metamorphic grades. Because these micas contain water, they control the melt fraction generated through dehydration melting in that a greater proportion of micas permits more extensive melting. Orogenic gold deposits, in which mineralization is typically encapsulated by potassic alteration, form at deep-enough crustal levels to survive repeated tectonic activity, which can lead to their being metamorphosed. In the vicinity of this metamorphosed gold mineralization, the greatest proportion of felsic melt is generated in the more metal-and sulfur-rich rocks because of the associated potassic alteration. Ore minerals dissolve and are physically incorporated into the resulting felsic melt, which thereby becomes metal-and sulfur-enriched. Since melt fraction is the dominant control on strain partitioning and melt mobilization, increased melting in K-altered mineralized rocks implies that these sites will be the first to experience melt escape and will continue to be the focus of melt escape during ongoing metamorphism. This strain partitioning promotes shear zone development, and once shearing is localized to K-altered mineralized domains, it may attract external magma, allowing extension and linking with nearby active shear zones. In this way, mineralized zones may connect to a regional network of magma transfer, allowing metal enrichment of migrating magmas. Terrains that underwent widespread K alteration associated with mid-crustal gold enrichment are likely, when metamorphosed, to produce significant volumes of reduced, relatively metal-and sulfur-enriched felsic magma. The ages and relative tectonic preservation potential of different K alteration-associated ore types implies that Au, Ag, As, Sb, Bi, Te, and W may be recycled within the crust through this mechanism, whereas Cu and Mo are unlikely to be recycled and require mantle sourcing to form new intrusion-related ores. Silicate melt derived from preexisting zones of gold enrichment in the lower crust may contribute significantly to the metal budget of intrusion-related gold systems, and possibly some gold-rich porphyry deposits

Risk Factors for the Development of Cataract in Children with Uveitis

PURPOSE: To determine the risk factors for the development of cataract in children with uveitis of any etiology. DESIGN: Cohort study. METHODS: Two hundred forty-seven eyes of 140 children with uveitis were evaluated for the development of vision-affecting cataract. Demographic, clinical, and treatment data were collected between the time of presentation and the first instance cataract was recorded or findings at final follow-up. Main outcome measures included the prevalence of cataract and distribution by type of uveitis, incidence of new onset cataract time to cataract development, and risk factors for the development of cataract. RESULTS: The prevalence of cataract in our cohort was 44.2% and was highest among eyes with panuveitis (77.1%), chronic anterior uveitis (48.3%), and intermediate uveitis (48.0%). The overall incidence of newly diagnosed cataract was 0.09 per eye-year, with an estimated 69% to develop uveitis-related cataract with time. The main factors related with cataract development were the number of uveitis flares per year (hazard ratio [HR] = 3.06 [95% confidence interval {CI}, 2.15–4.35], P < .001), cystoid macular edema (HR = 2.87 [95% CI, 1.41–5.82], P = .004), posterior synechia at presentation (HR = 2.85 [95% CI, 1.53–5.30], P = .001), and use of local injections of corticosteroids (HR = 2.37 [95% CI, 1.18–4.75], P = .02). Treatments with systemic and topical corticosteroids were not significant risk factors. CONCLUSIONS: In this study, we found that development of cataract is common among pediatric eyes with uveitis and is most strongly related to the extent of inflammation recurrences and ocular complications. We suggest that controlling the inflammation, even using higher doses of systemic and topical corticosteroids, is of importance in preventing ocular complications, such as cataract. Uveitis accounts for 10–15% of blindness in the developed world.1 Although pediatric uveitis is relatively uncommon, accounting for only 5–10% of all uveitis cases,2 it affects young patients, who in most cases are otherwise healthy. Vision loss results from ongoing inflammation that leads to ocular structural changes, such as cataract, corneal opacities, optic neuropathy, and retinal lesions. The most common causes of vision loss in children with uveitis are cataract, glaucoma, and chronic cystoid macular edema (CME).2, 3 In addition, any chronic visual obstruction can result in the development of amblyopia in younger children, with vision loss persisting after the inciting cause is treated.4 Such changes, together with the need for long-term treatment and continuous monitoring, can have a profound impact on their development, independence, and education. The prevalence of cataract in eyes with uveitis ranges from 20–64%,4, 5, 6, 7 and it is the most common complication of uveitis in children,8 occurring in approximately 35% of children with juvenile idiopathic arthritis (JIA)-associated uveitis9 and increasing ≤80% in adults.10, 11 Cataract progression can be the result of persistent intraocular inflammation,12, 13 can be caused by surgery for uveitis complications (eg, trabeculectomies and repair of retinal detachments), or can be a consequence of uveitis treatment, particularly the use of local or systemic corticosteroids.14, 15, 16, 17 It results in reduced visual acuity and can have a detrimental effect on the development and academic achievements of these children.18 Studies have examined risk factors for the development of cataract among children with JIA-associated uveitis, identifying risk factors such as the presence of posterior synechiae (PS) at presentation,12, 19 the use of systemic corticosteroids,13 topical corticosteroid therapy exceeding 3 drops a day,12 or persistent, uncontrolled active inflammation,3 while early treatment with methotrexate delayed cataract progression.19 However, JIA is a unique cause of uveitis, often localized to the anterior chamber, with frequent intraocular structural changes and the early use of systemic immunosuppressive agents. It may not represent the same risks as other causes of pediatric uveitis. We examined disease- and treatment-related risk factors for cataract development in children with uveitis of any etiology. We investigated clinical and ophthalmologic characteristics, as well as treatment strategies in relation to the time interval between the first presentation with uveitis and cataract development

Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells

Novel synthetic antagonists of retinoic acid receptors (RARs) have been developed. To avoid interference by serum retinoids when testing these compounds, we established serum-free grown sub-lines (>3 years) of the prostate carcinoma lines LNCaP, PC3 and DU145. A high affinity pan-RAR antagonist (AGN194310, Kd for binding to RARs = 2–5 nM) inhibited colony formation (by 50%) by all three lines at 16–34 nM, and led to a transient accumulation of flask-cultured cells in G1 followed by apoptosis. AGN194310 is 12–22 fold more potent than all-trans retinoic acid (ATRA) against cell lines and also more potent in inhibiting the growth of primary prostate carcinoma cells. PC3 and DU145 cells do not express RARβ, and an antagonist with predominant activity at RARβ and RARγ (AGN194431) inhibited colony formation at concentrations (∼100 nM) commensurate with a Kd value of 70 nM at RARγ. An RARα antagonist (AGN194301) was less potent (IC50 ∼200 nM), but was more active than specific agonists of RARα and of βγ. A component(s) of serum and of LNCaP-conditioned medium diminishes the activity of antagonists: this factor is not the most likely candidates IGF-1 and EGF. In vitro studies of RAR antagonists together with data from RAR-null mice lead to the hypothesis that RARγ-regulated gene transcription is necessary for the survival and maintenance of prostate epithelium. The increased potencies of RAR antagonists, as compared with agonists, suggest that antagonists may be useful in the treatment of prostate carcinoma. © 2001 Cancer Research Campaign http://www.bjcancer.co

60 million years of glaciation in the Transantarctic Mountains

The Antarctic continent reached its current polar location ~83 Ma and became shrouded by ice sheets ~34 Ma, coincident with dramatic global cooling at the Eocene-Oligocene boundary. However, it is not known whether the first Antarctic glaciers formed immediately prior to this or were present significantly earlier. Here we show that mountain glaciers were likely present in the Transantarctic Mountains during the Late Palaeocene (~60–56 Ma) and middle Eocene (~48–40 Ma). Temperate (warm-based) glaciers were prevalent during the Late Eocene (~40–34 Ma) and, in reduced numbers, during the Oligocene (~34–23 Ma), before larger, likely cold-based, ice masses (including ice sheets) dominated. Some temperate mountain glaciers were present during the Miocene Climatic Optimum (~15 Ma), before a widespread switch to cold-based glaciation. Our findings highlight the longevity of glaciation in Antarctica and suggest that glaciers were present even during the Early-Cenozoic greenhouse world

Impact of Zinc Supplementation on Subsequent Morbidity and Growth in Bangladeshi Children With Persistent Diarrhoea

This study was conducted to explore whether supplementation of zinc to children during persistent diarrhoea has any subsequent effect on morbidity and growth. A prospective follow-up study was conducted among children, aged 3-24 months, with persistent diarrhoea, who participated earlier in a double-blind randomized placebo-controlled trial. During persistent diarrhoea, children were randomly allocated to receive either zinc in multivitamin syrup or only multivitamin syrup for two weeks. After recovering from diarrhoea, 76 children in the multi-vitamin syrup and 78 children in the zinc plus multivitamin syrup group were followed up for subsequent morbidity and growth. Weekly morbidity and two-weekly anthropometric data were collected for the subsequent 12 weeks. Data showed that episodes and duration of diarrhoea were reduced by 38% and 44% respectively with supplementation of zinc. There was no significant difference in the incidence or duration of respiratory tract infection between the zincsupplemented and the non-supplemented group. Improved linear growth was observed in underweight children (weight-for-age &lt;70% of the National Center for Health Statistics standard) who received zinc compared to those who did not receive

Sexual selection protects against extinction

Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorised that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males, and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which depends on mutation load, then sexually selected filtering through ‘genic capture’ could offset the costs of sex because it provides genetic benefits to populations. Here, we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for ~7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress

Cumulate causes for the low contents of sulfide-loving elements in the continental crust

Despite the economic importance of chalcophile (sulfide-loving) and siderophile (metal-loving) elements (CSEs), it is unclear how they become enriched or depleted in the continental crust, compared with the oceanic crust. This is due in part to our limited understanding of the partitioning behaviour of the CSEs. Here I compile compositional data for mid-ocean ridge basalts and subduction-related volcanic rocks. I show that the mantle-derived melts that contribute to oceanic and continental crust formation rarely avoid sulfide saturation during cooling in the crust and, on average, subduction-zone magmas fractionate sulfide at the base of the continental crust prior to ascent. Differentiation of mantle-derived melts enriches lower crustal sulfide- and silicate-bearing cumulates in some CSEs compared with the upper crust. This storage predisposes the cumulate-hosted compatible CSEs (such as Cu and Au) to be recycled back into the mantle during subduction and delamination, resulting in their low contents in the bulk continental crust and potentially contributing to the scarcity of ore deposits in the upper continental crust. By contrast, differentiation causes the upper oceanic and continental crust to become enriched in incompatible CSEs (such as W) compared with the lower oceanic and continental crust. Consequently, incompatible CSEs are predisposed to become enriched in subduction-zone magmas that contribute to continental crust formation and are less susceptible to removal from the continental crust via delamination compared with the compatible CSEs

Cardiovascular Functional Reserve Before and After Kidney Transplant.

Importance: Restitution of kidney function by transplant confers a survival benefit in patients with end-stage renal disease. Investigations of mechanisms involved in improved cardiovascular survival have relied heavily on static measures from echocardiography or cardiac magnetic resonance imaging and have provided conflicting results to date. Objectives: To evaluate cardiovascular functional reserve in patients with end-stage renal disease before and after kidney transplant and to assess functional and morphologic alterations of structural-functional dynamics in this population. Design, Setting, and Participants: This prospective, nonrandomized, single-center, 3-arm, controlled cohort study, the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study, included patients with stage 5 chronic kidney disease (CKD) who underwent kidney transplant (KTR group), patients with stage 5 CKD who were wait-listed and had not undergone transplant (NTWC group), and patients with hypertension only (HTC group) seen at a single center from April 1, 2010, to January 1, 2013. Patients were followed up longitudinally for up to 1 year after kidney transplant. Clinical data collection was completed February 2014. Data analysis was performed from June 1, 2014, to March 5, 2015. Further analysis on baseline and prospective data was performed from June 1, 2017, to July 31, 2019. Main Outcomes and Measures: Cardiovascular functional reserve was objectively quantified using state-of-the-art cardiopulmonary exercise testing in parallel with transthoracic echocardiography. Results: Of the 253 study participants (mean [SD] age, 48.5 [12.7] years; 141 [55.7%] male), 81 were in the KTR group, 85 in the NTWC group, and 87 in the HTC group. At baseline, mean (SD) maximum oxygen consumption (V̇O2max) was significantly lower in the CKD groups (KTR, 20.7 [5.8] mL · min-1 · kg-1; NTWC, 18.9 [4.7] mL · min-1 · kg-1) compared with the HTC group (24.9 [7.1] mL · min-1 · kg-1) (P < .001). Mean (SD) cardiac left ventricular mass index was higher in patients with CKD (KTR group, 104.9 [36.1] g/m2; NTWC group, 113.8 [37.7] g/m2) compared with the HTC group (87.8 [16.9] g/m2), (P < .001). Mean (SD) left ventricular ejection fraction was significantly lower in the patients with CKD (KTR group, 60.1% [8.6%]; NTWC group, 61.4% [8.9%]) compared with the HTC group (66.1% [5.9%]) (P < .001). Kidney transplant was associated with a significant improvement in V̇O2max in the KTR group at 12 months (22.5 [6.3] mL · min-1 · kg-1; P < .001), but the value did not reach the V̇O2max in the HTC group (26.0 [7.1] mL · min-1 · kg-1) at 12 months. V̇O2max decreased in the NTWC group at 12 months compared with baseline (17.7 [4.1] mL · min-1 · kg-1, P < .001). Compared with the KTR group (63.2% [6.8%], P = .02) or the NTWC group (59.3% [7.6%], P = .003) at baseline, transplant was significantly associated with improved left ventricular ejection fraction at 12 months but not with left ventricular mass index. Conclusions and Relevance: The findings suggest that kidney transplant is associated with improved cardiovascular functional reserve after 1 year. In addition, cardiopulmonary exercise testing was sensitive enough to detect a decline in cardiovascular functional reserve in wait-listed patients with CKD. Improved V̇O2max may in part be independent from structural alterations of the heart and depend more on ultrastructural changes after reversal of uremia

Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

CONTEXT: The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. OBJECTIVE: To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. DESIGN: A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. RESULTS: Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. CONCLUSION: Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition