Climate velocities and species tracking in global mountain regions.

Mountain ranges contain high concentrations of endemic species and are indispensable refugia for lowland species that are facing anthropogenic climate change1,2. Forecasting biodiversity redistribution hinges on assessing whether species can track shifting isotherms as the climate warms3,4. However, a global analysis of the velocities of isotherm shifts along elevation gradients is hindered by the scarcity of weather stations in mountainous regions5. Here we address this issue by mapping the lapse rate of temperature (LRT) across mountain regions globally, both by using satellite data (SLRT) and by using the laws of thermodynamics to account for water vapour6 (that is, the moist adiabatic lapse rate (MALRT)). By dividing the rate of surface warming from 1971 to 2020 by either the SLRT or the MALRT, we provide maps of vertical isotherm shift velocities. We identify 17 mountain regions with exceptionally high vertical isotherm shift velocities (greater than 11.67 m per year for the SLRT; greater than 8.25 m per year for the MALRT), predominantly in dry areas but also in wet regions with shallow lapse rates; for example, northern Sumatra, the Brazilian highlands and southern Africa. By linking these velocities to the velocities of species range shifts, we report instances of close tracking in mountains with lower climate velocities. However, many species lag behind, suggesting that range shift dynamics would persist even if we managed to curb climate-change trajectories. Our findings are key for devising global conservation strategies, particularly in the 17 high-velocity mountain regions that we have identified.

Exploring U.S. Hispanic origin groups diagnosed with uterine cancer - Are there disparities?

OBJECTIVE: To evaluate patterns and trends of uterine cancer among Hispanic subgroups. METHODS: The United States Cancer Statistics (USCS), National Cancer Database (NCDB), and World Population Review were used to obtain data on incidence, demographic characteristics, and cancer histology. Joinpoint regression program was used for statistical analysis. RESULTS: Based on 2001-2017 USCS data, the overall incidence of uterine cancer was 27.46 vs. 23.29/100,000 in Hispanics vs. non-Hispanic Whites. There was an over 2-fold higher annual increase in the incidence in Hispanics (1.94%; p < 0.001) vs. Whites (0.85%; p < 0.001), particularly in local stage disease. There was an increase in grade 1 endometrioid carcinoma (1.48%; p < 0.001 vs. -0.52%; p = 0.1) and aggressive histologic subtypes (4.04% p = 0.000 vs. 2.53% p = 0.000) in Hispanics vs. Whites. Using the NCDB (2004-2015), we analyzed 17,351 Hispanics by subgroup (Mexican, South/Central American, Puerto Rican, Cuban, and Dominican). Over the 12 years, there was an increase in the proportion of uterine cancer diagnoses in all Hispanics (5.2% to 11.0%; p < 0.0001). Dominican patients experienced the largest increase in diagnosis (2.6% to 14.9%; p < 0.0001), the highest proportion of advanced disease at 28.0% (p < 0.0001), and the highest incidence of non-endometrioid histologies at 37.1% (p < 0.0001). World Population Review 2023 revealed the highest female obesity rates in Puerto Rico (51.4%), the Dominican Republic (34.1%), and Mexico (32.8%). CONCLUSION: Uterine cancer incidence is increased in Hispanics, with the largest increase in Dominican women with more advanced stages and high-risk histologic subtypes. The impact of obesity on cancer risk, especially in Puerto Ricans, Dominicans, and Mexicans, warrants further investigation.

The role of vein grafts in reconstructive head and neck microsurgery

Abstract Objective: Free tissue transfer is widely used for head and neck reconstruction. In certain circumstances, vein grafting is required to elongate free flap pedicles to connect them to appropriate recipient vessels. Because of controversy regarding the use of interposition vein grafts in free tissue reconstruction, this paper reports vein graft indications, techniques, safety, and outcomes for head and neck microvascular surgery. Methods: Twenty-six patients (23 men and 3 women) who underwent interposition vein grafting concurrent with free tissue transfer were included in this study. The most common reason for head and neck reconstruction with vein graft was tumor recurrence, followed by flap salvage. The interposition vein grafts were applied in two manners as temporary arteriovenous (A-V) loop and conduit to extend the length of the free flap for venous drainage. Results: The most common reconstructions were anterolateral thigh flaps (15 cases), followed by vastus lateralis myocutaneous (3 cases) and radial forearm (2 cases) flaps. The common recipient vessels were superior thyroid artery, superficial temporal artery and external jugular vein. The free flap loss rate was 7.7% with vein grafts and 4.9 without vein grafts (p = 0.380). The free flap complication rate was 50.0% and 16.8% in patients with and without vein grafts, respectively (p < 0.001). Radiation therapy, chemotherapy, prior neck dissection, and prior free flap transfer were more common in the vein graft group (all p < 0.001). The hospital stay was significantly longer for the vein graft group than for the non-vein graft group (29.5 vs. 19.0 days; p = 0.001). Conclusion: Overall free flap survival rates of 92.3% and 95.1% in the vein and non-vein graft groups, respectively - indicating the reliability of the vein grafts in challenging head and neck reconstructions, particularly in salvage cases and patients with multiple reconstructions. Level of evidence: Level 3.

The role of vein grafts in reconstructive head and neck microsurgery.

OBJECTIVE: Free tissue transfer is widely used for head and neck reconstruction. In certain circumstances, vein grafting is required to elongate free flap pedicles to connect them to appropriate recipient vessels. Because of controversy regarding the use of interposition vein grafts in free tissue reconstruction, this paper reports vein graft indications, techniques, safety, and outcomes for head and neck microvascular surgery. METHODS: Twenty-six patients (23 men and 3 women) who underwent interposition vein grafting concurrent with free tissue transfer were included in this study. The most common reason for head and neck reconstruction with vein graft was tumor recurrence, followed by flap salvage. The interposition vein grafts were applied in two manners as temporary arteriovenous (A-V) loop and conduit to extend the length of the free flap for venous drainage. RESULTS: The most common reconstructions were anterolateral thigh flaps (15 cases), followed by vastus lateralis myocutaneous (3 cases) and radial forearm (2 cases) flaps. The common recipient vessels were superior thyroid artery, superficial temporal artery and external jugular vein. The free flap loss rate was 7.7% with vein grafts and 4.9 without vein grafts (p = 0.380). The free flap complication rate was 50.0% and 16.8% in patients with and without vein grafts, respectively (p < 0.001). Radiation therapy, chemotherapy, prior neck dissection, and prior free flap transfer were more common in the vein graft group (all p < 0.001). The hospital stay was significantly longer for the vein graft group than for the non-vein graft group (29.5 vs. 19.0 days; p = 0.001). CONCLUSION: Overall free flap survival rates of 92.3% and 95.1% in the vein and non-vein graft groups, respectively - indicating the reliability of the vein grafts in challenging head and neck reconstructions, particularly in salvage cases and patients with multiple reconstructions. LEVEL OF EVIDENCE: Level 3.

Microbiomes of Velloziaceae from phosphorus-impoverished soils of the campos rupestres, a biodiversity hotspot.

The rocky, seasonally-dry and nutrient-impoverished soils of the Brazilian campos rupestres impose severe growth-limiting conditions on plants. Species of a dominant plant family, Velloziaceae, are highly specialized to low-nutrient conditions and seasonal water availability of this environment, where phosphorus (P) is the key limiting nutrient. Despite plant-microbe associations playing critical roles in stressful ecosystems, the contribution of these interactions in the campos rupestres remains poorly studied. Here we present the first microbiome data of Velloziaceae spp. thriving in contrasting substrates of campos rupestres. We assessed the microbiomes of Vellozia epidendroides, which occupies shallow patches of soil, and Barbacenia macrantha, growing on exposed rocks. The prokaryotic and fungal profiles were assessed by rRNA barcode sequencing of epiphytic and endophytic compartments of roots, stems, leaves and surrounding soil/rocks. We also generated root and substrate (rock/soil)-associated metagenomes of each plant species. We foresee that these data will contribute to decipher how the microbiome contributes to plant functioning in the campos rupestres, and to unravel new strategies for improved crop productivity in stressful environments.

Efficacy of green onion root extract in cosmetics and skin care products / Eficácia do extrato de raiz de cebola verde em cosméticos e produtos de cuidado da pele

In this study, leftover roots of Sansing green onions grown without toxic chemicals in Sansing Township, Ilan County, Taiwan were used as a raw material of skincare products. The raw material was extracted from the green onion roots by ultrasound in a low-temperature, safe and pollution-free environment. We hope to develop cleansers and other facial care products made of this natural, environmentally friendly, safe and affordable raw material so that people with sensitive skin can also use these products. We also hope that this study can contribute to circular economy and achieve the goal of green innovation by recycling the leftover roots. In terms of anti-oxidation, the DPPH free radical scavenging ability of 2.5 mg/mL green onion root extract was equivalent to 98% of that of 1 mg/mL BHT; the Fe2+ chelating ability was equivalent to 87.0% of that of 0.02 mg/mL EDTA; the superoxide anions scavenging ability of 2.5 mg/mL green onion root extract was equivalent to 84.2% of that of 1 mg/mL BHT and 80.4% of that of 0.05 mg/mL vitamin C. With respect to melanin synthesis inhibition, the green onion root extract's ability to inhibit dopachrome, the intermediate product of melanin, was positively correlated to its concentration, i.e., the higher the concentration of the green onion root extract, the better the inhibition ability. The IC50 of green onion root extract was 1.83 mg/mL, while, for comparison, the IC50 of vitamin C was 0.62 mg/mL. Furthermore, according to the cell survival assay, no obvious cytotoxic effect was found with the increase in the concentration of the green onion root extract. The whitening effect improved after 30 days of test. The improvement rate was 5.6% for 2.5 mg/mL green onion root extract, 3.1% for 1.25 mg/mL extract, and 1.7% for 0.625 mg/mL extract. The moisture retention also improved after 30 days of test. The moisture retention improvement rate was 22.7% for 2.5 mg/mL green onion root extract, 21.6% for 1.25 mg/mL extract, and 15.4% for 0.625 mg/mL extract. Based on the experiments, the green onion root extract obtained from ultrasound not only did not cause skin allergy and irritation but also showed anti-aging, melanin synthesis inhibition, whitening and moisture retention effects. The results showed that the green onion root extract can improve the moisture retention and whitening effect of the mask.

Neste estudo, restos de raízes de cebolinhas Sansing, cultivadas sem produtos químicos tóxicos no município de Sansing, Condado de Ilan, Taiwan, foram utilizadas como matéria-prima de produtos para a pele. A matéria-prima foi extraída das raízes de cebolinha por ultrassom em um ambiente de baixa temperatura, seguro e livre de poluição. Esperamos desenvolver produtos de limpeza e outros produtos para cuidados faciais produzidos com essa matéria-prima natural, ecologicamente correta, segura e acessível, para Improvement rate (%) Moisture retention Whitening effect 7.65 1.29 que pessoas com pele sensível também possam usar esses produtos. Também esperamos que este estudo possa contribuir para a economia circular e alcançar o objetivo da inovação ecológica, reciclando restos das raízes. Em termos de anti-oxidação, a capacidade de sequestro do radical livre DPPH de 2,5 mg/mL de extrato de raiz de cebolinha foi equivalente a 98% de 1 mg/mL de BHT; a capacidade quelante do Fe2+ foi equivalente a87,0% de 0,02 mg/mL de EDTA; a capacidade de sequestro de ânions superóxidos de 2,5 mg/mL de extrato de raiz de cebolinha foi equivalente a 84,2% de 1 mg/mL BHT e 80,4% de 0,05 mg/mL de vitamina C. No que diz respeito à inibição da síntese de melanina, a capacidade do extrato de raiz de cebolinha de inibir o dopacrômio, o metabolito intermediário de melanina, foi positivamente correlacionada com a sua concentração, ou seja, quanto maior a concentração do extrato de raiz de cebolinha, maior a capacidade de inibição. O IC50 de extrato de raiz de cebolinha foi de 1,83 mg/mL, enquanto que, por comparação, o IC50 de vitamina C foi de 0,62mg/mL. Além disso, de acordo com o ensaio de sobrevivência celular, nenhum efeito citotóxico foi observado com o aumento da concentração do extrato de raiz de cebolinha. O efeito de branqueamento melhora após 30 dias de ensaio. A melhoria foi de 5,6% para 2,5 mg/mL de extrato de raiz de cebolinha, 3,1% para 1,25 mg/mL de extrato e 1,7% para 0,625 mg/mL de extrato. A retenção de umidade também melhorou depois de 30 dias de teste. A taxa de melhoria de retenção de umidade foi de 22,7% para 2,5 mg/mL de extrato de raiz de cebolinha, 21,6% para 1,25 mg/mL de extrato, e 15,4% para 0,625 mg/mL de extrato.Com base nas experiências efetuadas, o extrato de raiz de cebolinha obtida por ultrassom não só não causa alergia nem irritação da pele, mas também demonstrou atividade anti-envelhecimento, inibição da síntese de melanina, capacidade de branqueamento e retenção de umidade. Os resultados mostraram que o extrato de raiz de cebolinha pode melhorar a retenção de umidade e efeito de branqueamento da máscara.

Efficacy of rice bran fermentation in cosmetics and skin care products / Eficácia da fermentação de farelo de arroz em cosméticos e produtos para cuidados com a pele

This study aims to develop rice bran-based skin care products with moisturizing, whitening and anti-wrinkle effects similar to Pitera (a natural by-product of sake lees fermentation) but without alcohol irritation for sensitive skin. To achieve this objective, bran from organic indica rice was fermented by lactic acid bacteria in a safe and pollution-free environment. In terms of anti-oxidation, the DPPH ．free radical scavenging ability of 100.0 mg/mL bran fermentation solution was 71.4% of that of vitamin C of the same concentration; and its Fe2+ chelating ability was 79.0% of that of EDTA of the same concentration. Moreover, the superoxide anion scavenging ability of 10.0 mg/mL bran fermentation solution was equivalent to 42.9% of that of BHT of similar concentration. With respect to inhibition of melanin synthesis, the bran fermentation solution's ability to inhibit the synthesis of dopachrome, the intermediate of melanin, was positively correlated to its concentration, i.e., the higher the concentration of the bran fermentation solution was, the better the inhibition ability was. The IC50 of bran fermentation solution was 9.23 mg/mL while, for comparison, that of arbutin was 0.52 mg/mL. Furthermore, according to the cell survival assay, no obvious cytotoxic effect was found with the increase of the concentration of the bran fermentation solution. As for whitening evaluation, the whitening improvement rate was 9.29% in 20% dilution, 5.36% in 15% dilution, 3.69% in 10% dilution, 2.43% in 5% dilution, 0.35% in 1% dilution in a 30-day test. In the moisturizing evaluation, the moisturizing improvement rate was 44.31% in 20% dilution, 20.48% in 15% dilution, 7.68% in 10% dilution, 6.02% in 5% dilution and 2.02% in 1% dilution. Based on the experimental results, the alcohol-free rice bran fermentation solution not only did not cause irritation but also had antiaging, melanin synthesis inhibition, whitening and moisturizing effects. Therefore, it is advisable to add rice bran fermentation solution to cleaning mousse, shower gel, serum and essence to turn bran from compost of agricultural waste (cradle to grave) into a natural raw material (cradle to cradle) of the cosmetic industry, creating new value of rice bran.

Este estudo tem como objetivo desenvolver produtos de cuidados com a pele baseados em farelo de arroz com hidratação, branqueamento e efeitos antiarrugas semelhantes à Pitera (um subproduto natural da fermentação de sauces), mas sem irritação com álcool para a pele sensível. Para alcançar esse objetivo, o farelo do arroz indica orgânico foi fermentado por bactérias do ácido lático em um ambiente seguro e livre de poluição. Em termos de antioxidação, a capacidade de eliminação radical de DPPH.free de 100,0 mg / mL de solução de fermentação de farelo foi de 71,4% da vitamina C da mesma concentração; E sua capacidade de quelação Fe2 + foi de 79,0% da EDTA da mesma concentração. Além disso, a capacidade de eliminação de aniões superóxido de 10,0 mg / mL de solução de fermentação de farelo era equivalente a 42,9% da BHT de concentração similar. Com relação à inibição da síntese de melanina, a capacidade da solução de fermentação do farelo de inibir a síntese do dopachrome, o intermediário da melanina, correlacionou-se positivamente com sua concentração, ou seja, quanto maior a concentração da solução de fermentação do farelo, melhor a capacidade de inibição estava. A solução de IC50 de fermentação de farelo foi de 9,23 mg / mL enquanto que, para comparação, a arbutina era de 0,52 mg / mL. Além disso, de acordo com o ensaio de sobrevivência celular, nenhum efeito citotóxico óbvio foi encontrado com o aumento da concentração da solução de fermentação de farelo. Quanto à avaliação do branqueamento, a taxa de branqueamento foi de 9,29% na diluição de 20%, 5,36% na diluição de 15%, 3,69% na diluição de 10%, 2,43% na diluição de 5%, 0,35% na diluição de 1% em um teste de 30 dias . Na avaliação hidratante, a taxa de melhora hidratante foi de 44,31% em 20% de diluição, 20,48% em diluição de 15%, 7,68% em diluição de 10%, 6,02% em diluição de 5% e 2,02% em diluição a 1%. Com base nos resultados experimentais, a solução de fermentação de farelo de arroz sem álcool não só não causou irritação, mas também teve anti-envelhecimento, inibição da síntese de melanina, branqueamento e efeitos hidratantes. Portanto, é aconselhável adicionar solução de fermentação de farelo de arroz para mousse de limpeza, gel de banho, soro e essência para transformar o farelo do composto de resíduos agrícolas (berço a túmulo) em uma matéria-prima natural (berço para berço) da indústria de cosméticos, criando Novo valor do farelo de arroz.

Potent efficacy of combined PI3K/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia.

Philadelphia chromosome (Ph)-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is associated with activated JAK/STAT, Abelson kinase (ABL), and/or phosphatidylinositol 3-kinase (PI3K) signaling and poor clinical outcomes. PI3K pathway signaling inhibitors have been minimally investigated in Ph-like ALL. We hypothesized that targeted inhibition of PI3Kα, PI3Kδ, PI3K/mTOR, or target of rapamycin complex 1/2 (TORC1/TORC2) would decrease leukemia proliferation and abrogate aberrant kinase signaling and that combined PI3K pathway and JAK inhibition or PI3K pathway and SRC/ABL inhibition would have superior efficacy compared to inhibitor monotherapy. We treated 10 childhood ALL patient-derived xenograft models harboring various Ph-like genomic alterations with 4 discrete PI3K pathway protein inhibitors and observed marked leukemia reduction and in vivo signaling inhibition in all models. Treatment with dual PI3K/mTOR inhibitor gedatolisib resulted in near eradication of ALL in cytokine receptor-like factor 2 (CRLF2)/JAK-mutant models with mean 92.2% (range, 86.0%-99.4%) reduction vs vehicle controls (P < .0001) and in prolonged animal survival. Gedatolisib also inhibited ALL proliferation in ABL/platelet-derived growth factor receptor (PDGFR)-mutant models with mean 66.9% (range, 42.0%-87.6%) reduction vs vehicle (P < .0001). Combined gedatolisib and ruxolitinib treatment of CRLF2/JAK-mutant models more effectively inhibited ALL proliferation than either inhibitor alone (P < .001) and further enhanced survival. Similarly, superior efficacy of combined gedatolisib and dasatinib was observed in ABL/PDGFR-mutant models (P < .001). Overall, PI3K/mTOR inhibition potently decreased ALL burden in vivo; antileukemia activity was further enhanced with combination inhibitor therapy. Clinical trials testing combinations of kinase inhibitors in Ph-like ALL patients are indicated.

Population structure and demographic history of Sicyopterus japonicus (Perciformes; Gobiidae) in Taiwan inferred from mitochondrial control region sequences.

The amphidromous goby Sicyopterus japonicus is distributed throughout southern Taiwan and Japan. Larvae of this freshwater fish go through a long marine stage. This migratory mode influences population genetic structure. We examined the genetic diversity, population differentiation, and demographic history of S. japonicus based on the mitochondrial DNA control region. We identified 102 haplotypes from 107 S. japonicus individuals from 22 populations collected from Taiwan and Islet Lanyu. High mean haplotype diversity (h = 0.999) versus low nucleotide diversity (θπ = 0.008) was detected across populations. There was low correspondence between clusters identified in the neighbor-joining tree and geographical region, as also indicated by AMOVA and pairwise F(ST) estimates. Both mismatch distribution analysis and Tajima's D test indicated that S. japonicus likely experienced a demographic expansion. Using a Bayesian skyline plot approach, we estimated the time of onset of the expansion of S. japonicus at 135 kyr (during the Pleistocene) and the time of stable effective population size at approximately 2.5 kyr (last glacial maximum). Based on these results, we suggest 1) a panmictic population at the oceanic planktonic larval stage, mediated by the Kuroshio current; 2) a long planktonic marine stage and long period of dispersal, which may have permitted efficient tracking of environmental shifts during the Pleistocene; and 3) a stable, constant population size ever since the last glacial maximum.

Effects of the insertion of a nonapeptide from murine IL-1beta on the immunogenicity of carrier proteins delivered by live attenuated Salmonella.

A nonapeptide from IL-1beta has been reported to be an immunostimulant and adjuvant. To investigate the possibility of enhancing the immunogenicity of recombinant antigens delivered by live-attenuated Salmonella strains, we inserted an oligonucleotide coding for the nonapeptide from murine IL-1beta into the genes of three model proteins: LamB, MalE, and flagellin. The hybrid proteins were expressed and delivered in vivo by Salmonella aroA strains, and serum antibody responses were analyzed. The results showed that the nonapeptide induced an increase in the immune response against Salmonella-delivered flagellin, measured on day 28 post-immunization. However, the adjuvant effect was lost by day 42. In no case was an adjuvant effect detected for Salmonella-delivered LamB or MalE. Thus, by comparing the immune responses raised by purified MalE with and without the peptide, we investigated whether the insertion of the peptide affected the immunogenicity of the protein itself. Also in this case, a modest adjuvant effect was shown only after primary immunization and when very low doses of antigen were used. In conclusion, the immunomodulatory properties of the IL-1beta peptide can also be detected when it is delivered in vivo by Salmonella; however, the effect is modest and antigen-dependent.

Cloning and characterization of an alpha-amylase gene from Streptomyces sp WL6.

An alpha-amylase gene from Streptomyces sp WL6 was cloned on a 3.1kb DNA fragment, which was completely sequenced. The 3088 nucleotide sequence obtained contains three putative coding regions in the same orientation. The one corresponding to the structural region of the alpha-amylase gene has a deduced amino acid sequence of 459 residues, showing up to 71% identity to other alpha-amylases. An incomplete ORF was identified upstream the alpha-amylase gene, and the deduced product presents some homology to proteins involved in catabolic regulation.

Human T lymphotropic virus (HTLV) type I and II DNA amplification in HTLV-I/II-seropositive blood donors of the French West Indies.

To confirm the presence of DNA from human T lymphotropic virus type I (HTLV-I), HTLV-II, or both in individuals found HTLV-I/II-positive through systematic screening of blood donations in Guadeloupe (French West Indies), 42 blood donors repeatedly positive for HTLV-I/II by ELISA were studied by polymerase chain reaction (PCR). Three primer pairs (env, pol, tax) targeted on conserved regions of HTLV-I or -II sequences (or both) and six probes (two generic, two HTLV-I-specific, two HTLV-II-specific) were used in a multiplex PCR. HTLV-I sequences were detected in 31 individuals (74%). All 31 subjects positive by Western blot (WB) harbored HTLV-I sequences. Fifteen individuals (48%) were positive with the three primer pairs used, 10 (32%) with two, and 6 (20%) with one. Subjects indeterminate or negative by WB were all negative by PCR. No HTLV-II sequences were detected with specific probes. The results indicate the absence of HTLV-I and -II infection in individuals with indeterminate WB, the presence of HTLV-I DNA in individuals positive for WB in the French West Indies, and the absence of HTLV-II infection in the cohort.

Quantification of HTLV-1 proviral copy number in peripheral blood of symptomless carriers from the French West Indies.

The development of human T-cell leukemia type 1 (HTLV-1) diseases are related to an increase in the proviral copy number (VCN) in peripheral blood mononuclear cells (PBMCs). Twenty symptomless anti-HTLV-1-positive blood donors, as well as four symptomatic individuals, all from the French West Indies, were studied. The VCN in PBMCs was determined by quantitative PCR. The VCN values for asymptomatic HTLV-1 carriers (range of less than 100 to approximately 9,500/micrograms of DNA) was nearly always less than the values for symptomatic carriers (range of approximately 5,500 to approximately 29,000/micrograms of DNA). Consequently, the proportion of HTLV-1-infected PBMCs in symptomless and in symptomatic individuals ranged from less than 1/1,500 to approximately 1/16 and approximately 1/27 to approximately 1/5, respectively. No correlation could be found between VCN and age or sex, suggesting the importance of factors other than age and sex as influences on the VCN number.

Pathogenesis of early neonatal hypocalcemia: studies of serum calcitonin, gastrin, and plasma glucagon.

In 64 maternal-infant pairs, we tested the hypotheses that serum calcitonin, serum gastrin, and plasma glucagon concentrations are elevated in infants at risk for early neonatal hypocalcemia, and that elevated serum gastrin and plasma glucagon result in elevated serum calcitonin and low serum calcium values in neonates. Serum Ca declined significantly in neonates at 24 hours of age, and was inversely correlated with serum calcitonin. Cord serum calcitonin, gastrin, and plasma glucagon concentrations rose significantly at 24 hours of age. Cord calcitonin was significantly higher in preterm compared with term infants, and there was no significant difference between asphyxiated and nonasphyxiated preterm neonates; in term neonates cord calcitonin concentration was inversely correlated with Apgar scores at 1 and 5 minutes. Cord calcitonin was not correlated with cord gastrin or glucagon. Cord and 24-hour gastrin and glucagon values were not related to prematurity; cord glucagon, but not gastrin, was related to birth asphyxia. We conclude that (1) serum calcitonin, gastrin, and plasma glucagon values rise postnatally; cord calcitonin is elevated in preterm and in asphyxiated term infants; serum calcitonin concentration does not correlate with the elevated serum gastrin and plasma glucagon values; and at 24 hours of age, decreased serum Ca is correlated with serum calcitonin, and hence calcitonin might play a role in the pathogenesis of early neonatal hypocalcemia.

Serum calcitonin response to administration of calcium in newborn infants during exchange blood transfusion.

In 25 newborn infants, 30 "exchange" transfusions were performed. Pre-exchange serum calcitonin concentrations of newborn infants were higher than those of normal adults and of donor blood used for exchange transfusion. A gradual decline of serum calcitonin concentrations was observed with increasing postnatal age. Serum calcium and magnesium concentrations were inversely related to serum calcitonin concentrations. Newborn infants had significant elevations of serum calcitonin values within a few minutes after the administration of calcium. Gestationally younger infants (less than or equal to 33 weeks) had significantly more pronounced and swifter elevations of serum calcitonin concentrations after calcium administration than gestationally more mature infants (less than 33 weeks). We speculate that calcitonin may be an important "fetal hormone" and that increased calcitonin concentrations may relate to the pathogenesis of neonatal hypocalcemia.

The role of postnatal age and magnesium on parathyroid hormone responses during "exchange" blood transfusion in the newborn period.

One hundred and eight "exchange" blood transfusions were done on 61 newborn infants. Baseline serum PTH concentrations and the PTH rise in response to citrate-induced hypocalcemia were studied. Baseline PTH values increased with postnatal age, particularly after the first three days of life. The acute response of PTH to citrate-induced hypocalcemia appears within ten minutes following the initiation of exchange transfusion and was shortlived in spite of further decline of serum ionized calcium. The dominant effect of postnatal age over gestational age was demonstrated: postnatally older but gestationally less mature infants exhibited greater responsiveness than postnatally younger, but gestationally more mature, infants. The PTH response during exchange transfusion was blunted in hypomagnesemic infants. Since lower serum magnesium concentrations were also present during the first three days of life, a separate effect of serum magnesium concentrations on parathyroid responsiveness cannot be ruled out in this study.

Neonatal hypermagnesemia: effect on parathyroid hormone and calcium homeostasis.

Twenty pre-eclamptic mothers treated with MgSO4 and their newborn infants were studied prospectively to determine the clinical and biochemical effects of hypermagnesemia. Maternal serum magnesium concentration rose to 4.4 mg/dl at delivery and was accompanied by a fall in maternal serum calcium concentration during labor. Neonatal serum Mg concentration remained elevated for the first 72 hours of life (mean at 72 hours = 3.0 mg/dl). Serum Mg concentration was higher in premature infants and in babies with birth asphyxia and/or hypotonia. Serum Ca concentration was higher and serum PTH was lower in hypermagnesemic study infants when compared to a retrospectively selected, matched froup of control infants. We speculate that elevated serum Mg values in these infants result in a shift of Ca from bone to plasma, and that elevated Mg and Ca concentrations further suppress neonatal parathyroid function.

1,25-Dihydroxyvitamin D3 in childhood hepatic osteodystrophy.

Osteodystrophy frequently accompanies severe childhood hepatobiliary disease. Proposed causes include malabsorption of vitamin D and calcium, and diminished 25-hydroxylation of vitamin D. Two children, ages 23 and 35 months, with radiographic and biochemical evidence of rickets with extrahepatic biliary atresia, were treated with 1,25-dihydroxyvitamin D3. The minimal effective therapeutic dose and efficacy of 1,25-(OH)2D3 in the treatment of rickets associated with severe childhood hepatic disease were determined. Oral 1,25-(OH)2D3 was ineffective at doses of 0.10 microgram/kg/day. Parenteral doses of 0.20 microgram/kg/day effectively produced radiographic, bone mineral (photon absorptiometric), and biochemical evidence of healing. The need for four times the physiologic dose of 1,25-(OH)2D3 by the parenteral route suggested enhanced catabolism of, or end-organ resistance to, 1,25-(OH)2D3 in our patients with severe cholestatic liver disease treated with phenobarbital.

Urinary phosphate and cyclic AMP excretion following citrate-induced hypocalcemic stimulation of the neonatal parathyroid glands.

Sixteen neonates, ranging in gestational age from 27 to 41 weeks and in postnatal age from birth to 8 days, were evaluated for their renal response to an endogenous PTH stimulus in 22 separate experiments. The PTH stimulus was generated by the decreased serum ionized Ca that accompanies exchange transfusion with citrated blood. The neonates increased their serum PTH from 95.8 +/- 13.1 to 133.9 +/- 15.4 microliterEq/ml (mean +/- SEM) during the transfusion, while increasing their urinary cAMP from 0.77 +/- 0.11 to 1.45 +/- 0.22 nmol/ml, and their urinary P from 12.9 +/- 2.6 to 30.6 +/- 6.1 mg/dl in the four hours following the exchange transfusion. This response was not related to postnatal or gestational age. We speculate that lack of renal responsiveness to PTH does not play a major role in the pathogenesis of early neonatal hypocalcemia.