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PubMed1975

Influence of changes in arterial PCO2 on cerebral blood flow and cerebral energy state during hypothermia in the rat.

In order to study the relationship between arterial PCO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artifically ventilated rats was decreased to 22 degreesC, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVDO2) at PaCO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37 degrees C) over the PaCO2 range 15-60 mm Hg. Separate experiments were performed to evaluate CBF and CMRO2 at 22 degrees C and a PaCO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at PaCO2 values of 15, 30 and 60 mm Hg. The results showed that changes in CBF were of the same relative magnitude in hypothermia and normothermia when PaCO2 was increased from about 35 to about 60 mm Hg. However, with a decrease in PaCO2 the reduction in CBF was much more pronounced in hypothermia, and at PaCO2 15 Mm Hg CBF was less then 20% of the value measured in normothermic and normocapnic animals. The results of the metabolite measurements gave no evidence of tissue hypoxia in spite of the pronounced reduction in CBF. Although the results demonstrate that the brain of a hypothermic animal is protected against the harmful effects of a lowered CBF, it may not warrant recommending hyperventilation in clinical cases of hypothermia, especially not in patients with arteriosclerosis or cerebrovascular diseases.

Adenosine Diphosphate↗
PubMed1979

Behavioral treatment of caffeinism: reducing excessive coffee drinking.

Excessive coffee drinking can have deleterious effects because of the large amounts of caffeine that are ingested. Caffeine is thought to be addicting, and prolonged and excessive use can lead to caffeinism, a condition that has serious behavioral and physiological side effects. The present study developed and evaluated a treatment program to reduce excessive daily coffee drinking to moderate and presumably safer levels. Three habitual coffee drinkers received individualized changing criterion programs that systematically and gradually reduced their daily caffeine intake. The coffee drinkers were required to self-monitor and plot their daily intake of caffeine. They received monetary prizes for not exceeding the treatment phase criteria and forfeited a portion of their pretreatment deposit when they did. Their coffee drinking decreased from almost nine cups per day (over 1100 mg of caffeine) during baseline to less than three cups per day (less than 343 mg) at the end of treatment or a reduction of 69%. The treatment effect was maintained during a 10-month follow-up, averaging a 67% reduction from baseline. The program appears to be a reasonable method of reducing and then maintaining daily caffeine intake at less harmful levels.

Behavior Therapy↗
PubMed1979

Outcome of pregnancy in women using different methods of contraception.

During the years 1968-74, 17,032 women were recruited to the Oxford Family Planning Association prospective study of the effects of different methods of contraception. The present analysis, which concerns 5700 pregnancies experienced by the participants in the investigation, adds to the evidence that ex-users of oral contraceptives and intrauterine devices suffer no delecterious effects on the outcome of pregnancy in terms of miscarriage, ectopic gestation, stillbirth, congenital malformation, alteration in the sex ratio or reduction in birth weight. Accidental pregnancies in women taking oral contraceptives were few in the present study (66 in all), but it seems likely that harmful effects of exposure of the fetus to the pill in utero, if any, occur infrequently. Women experiencing an accidental pregnancy with an intrauterine device in situ are at a markedly increased risk of miscarriage and ectopic gestation and are more likely to give birth to an underweight infant than other women.

Abnormalities, Drug-Induced↗
PubMed1976

An ammonia-oxidizing bacterium, Nitrosovibrio tenuis nov. gen. nov. sp.

An ammonia-oxidizing, autotroph growing, slender, curved rod was isolated from the soil of Hawaii. It is well distinguishable from any other nitrifying bacteria thus far described by their morphology. The cells are 1.1-3.0 mum long and 0.3-0.4 mum wide. They are motile by means of 1-4 subpolar to lateral flagella. In contrast to most of the ammonia-oxidizing bacteria the isolated vibrio is void of an extensive cytomembrane system. To categorize this not yet described species we propose to create the new genus Nitrosovibrio and to classify the isolated strain as Nitrosovibrio tenuis.

Ammonia↗
PubMed1978

Cannabis, 1977.

Recent advances in development of immunoassay methods for marijuana constituents in body fluids provide a rapid means of detection for forensic purposes and a useful research tool for accurate quantitation of dose-response relation. Therapeutic possibilities of cannabis, such as reduction in intraocular pressure and bronchodilatation, may stimulate development of synthetic cannabinoid derivatives that meet acceptable standards of safety and effiicacy for treatment of glaucoma and asthma. Cannabis use may have harmful short- and long-term impacts on health. Potentially serious short-term effects include predisposition to angina during exercise in patients with coronary artery disease. Even in healthy subjects, marijuana smoking decreases peak exercise performance, possibly because of its chronotropic effect with achievement of maximum heart rate at reduced work loads. Although no conclusive evidence exists for long-term biologic consequences of chronic cannabis use, preliminary evidence, suggesting impairment in pulmonary function and immune responses, requires further investigation with large-scale epidemiologic studies.

Animals↗
PubMed1979

[Falsely positive values in multi-channel analysis: an estimation of their frequency with Sylvester's formula and their reduction by a multivariate test quantity (author's transl)].

The application of the binomial distribution for determining the number of "falsely positive values" is not suitable because of the partly strong correlations between the clinical chemical parameters. We have therefore tried to obtain more precise estimations for the number of falsely positive values by using a generalisation from Sylvester's formula and taking into account the correlations. We use multivariate statistics for testing a patient's value" when several laboratory parameters are simultaneously considered. The multivariate technique leads firstly to a significant reduction of the erroneously interpreted "falsely positive values" and secondly allows the detection of hidden implausible constellations of values.

Autoanalysis↗
PubMed2026

PEStimate: predicting offspring disease risk after polygenic embryo screening.

MOTIVATION: Polygenic embryo screening (PES) is a new, controversial technology, whereby human in vitro fertilization embryos are screened for their genetic risk of complex, polygenic diseases. PES aims to reduce the disease burden in offspring by prioritizing the selection of low-risk embryos. However, given that polygenic diseases are usually late-onset, PES outcomes must be estimated by epidemiological modeling. The liability threshold model has been previously used to predict outcomes. However, predictions rely on complex sets of equations, some of which require numerical integration or simulation. Further, previous models failed to account for the possibility that the selected embryo will not be born. RESULTS: Here, we present PEStimate, a freely available online app for predicting PES outcomes when screening for a single disease. PEStimate predicts the offspring risk with and without PES, as well as generates plots of the risk reduction versus key parameters. Users can adjust the number of available embryos, the live birth rate, the disease prevalence, the accuracy of the genetic risk predictor, the embryo selection method, the genetic risk of parents, and the disease status of parents, siblings, uncles/aunts, and grandparents of the embryos. Our model includes, for the first time, the possibility of embryo implantation failure, showing that risk reductions have been previously overestimated. PEStimate provides geneticists, healthcare professionals, patients, and other stakeholders with a necessary tool for examining the impact of PES and weighing its potential benefits against possible personal and societal harms. AVAILABILITY AND IMPLEMENTATION: PEStimate: https://polygenicembryo.shinyapps.io/pestimate. Source code: https://github.com/Lirazk/PEStimate.

Humans↗
PubMed1979

Blood and blood substitutes: current practice.

We have seen that the vast majority of previously healthy patients can tolerate a significant reduction in red cell mass without adverse effect on oxygen consumption. For these patients, volume replenishment with electrolyte solutions will adequately restore blood volume and cardiac output. Colloid solutions offer no advantage over electrolyte solutions, certainly are more expensive and may even be harmful. For patients who need restoration of oxygen-carrying capacity, washed, packed red cell administration is the therapy of choice, and frozen, thawed red cells represent optimal utilization of a scarce commodity. Other components, such as fresh frozen plasma, factor VIII or IX concentrates and platelets, are not indicated unless a specific deficiency exists. Autologous blood, using one of the techniques described above, is a safe and effective means of replacing lost red cells in special circumstances. The use of these techniques, combined with realistic ordering of homologous blood for elective surgical procedures, should act in concert to relieve shortages of blood.

Albumins↗
PubMed1979

Surgical repair of a comminuted distal femoral fracture in a dog.

This case illustrates that good results may be achieved with fractured femur that was severely comminuted (i.e. a "Humpty Dumpty" fracture). The blood supply at the fracture site must be carefully preserved. The bony architecture must be reestablished with perfect reduction of the articular surfaces, preferably with interfragmentary compression between the bone fragments. These fragments are held in place with screws and Kirschner wires. Some of the screws and pins were left in place as the trauma incurred to retrieve them would have done more harm than good due to bony overgrowth.

Animals↗
PubMed2025

Multi-Omics Platforms Reveal Synergistic Intestinal Toxicity in Tilapia from Acute Co-Exposure to Polystyrene Microplastics, Sulfamethoxazole, and BDE153.

Polystyrene microplastic (MP) and its co-existing contaminants may exert different toxic effects on its surrounding aquatic organisms. In order to detect the intestinal harmful responses, tilapia were subjected to exposure with 75 nm of MPs, 100 ng·L-1 of sulfamethoxazole (SMZ), 5 ng·L-1 of BDE153, and combinations thereof over periods of 2, 4, and 8 days. Enzymatic assays, transcriptomics, proteomics, and metabolomics were employed to evaluate intestinal histopathological effects. Results showed that significant reductions were observed in ATP, ROS, SOD, EROD, lipid metabolism-related enzymes, pro-inflammatory cytokines (TNFα and IL-1β), and apoptosis marker caspase 3 across all groups at day 8. Histological evaluation revealed diminished goblet cell density, with distinct vacuole formation in the BDE153+MPs group. KEGG pathway analysis highlighted disruptions in endocytosis, MAPK signaling, phagosome formation, and actin cytoskeleton regulation. Proteomic findings indicated notable enrichment in endocytosis (decreased sorting nexin-2; increased Si:dkey-13a21.4), MAPK/PPAR signaling, protein processing in the endoplasmic reticulum (Sec61 subunit gamma), and cytoskeletal modulation (reduced fibronectin; elevated activation peptide fragment 1), with or without SMZ and BDE153. Metabolomic profiling showed significant alterations in ABC transporters, aminoacyl-tRNA biosynthesis, protein digestion and absorption, and linoleic acid metabolism. In summary, these findings suggest that BDE153 and MPs synergistically exacerbate intestinal damage and gene/protein expression over time, while SMZ appears to exert an antagonistic, mitigating effect.

Animals↗
PubMed2026

Neonatal outcomes following antenatal corticosteroid administration before planned caesarean birth at late preterm or early term (36-38 weeks' gestation): a retrospective cohort study.

OBJECTIVE: To investigate the benefits and harms associated with antenatal corticosteroids (ACS) prior to planned caesarean birth at late preterm or early term. DESIGN: Retrospective cohort study. SETTING: South Australia, Australia, 2005-2018. PATIENTS: Women with singleton pregnancies undergoing planned caesarean birth between 36+0 and 38+6 weeks' gestation. METHODS: We used routinely collected electronic maternity and neonatal data. Adjusted risk differences (aRD) with 95% CIs were calculated for neonatal and maternal outcomes. OUTCOME MEASURES: Neonatal outcomes included respiratory distress requiring oxygen, hypoglycaemia requiring glucose, neonatal unit (NNU) admission and prolonged NNU admission (≥48 hours). RESULTS: Among the cohort of 4049 women, the proportion receiving ACS was 54.8%, 48.4% and 5.6% at 36, 37 and 38 completed weeks' gestation, respectively. ACS administration was associated with a significant reduction in respiratory distress across all gestations, with the greatest reduction seen at 36 weeks' gestation (aRD -12.5%; 95% CI -21.4% to -3.6%). At 38 weeks' gestation, ACS administration was associated with an increased risk of neonatal hypoglycaemia (aRD 5.7%; 95% CI 1.1% to 10.2%), NNU admission (aRD 5.4%; 95% CI 0.1% to 10.7%) and prolonged NNU admission (aRD 4.6%; 95% CI 0.2% to 8.9%). CONCLUSIONS: ACS administration prior to late preterm and early term planned caesarean birth was associated with reduced risk of respiratory distress. The net benefit of ACS administration before planned caesarean birth remains unclear; however, there was evidence of potential neonatal harm when birth occurred after 37 weeks' gestation.

Epidemiology↗
PubMed1975

Corticosteroids increase superoxide anion production by rat liver microsomes.

Superoxide anion production by liver microsomes from intact, adrenalectomized, and cortisoltreated adrenalectomized rats has been determined. The amount formed was roughly proportionate to the amount of cortisol given, and a similar response was seen in the activity of NADPH-cytochrome c reductase. The amount of measurable superoxide anion was markedly reduced by the addition of superoxide dismutase. The increased production of this potent free radical with cortisol therapy suggests that its formation may contribute to some of the harmful effects of corticosteroids given in more than physiologic amounts.

Adrenalectomy↗
PubMed1976

Exposure to drugs and other possibly harmful factors during the first trimester of pregnancy. Comparison of two prospective studies performed in Sweden 10 years apart.

474 women in mid-pregnancy, interviewed at ten different hospitals in Sweden, were questioned on a number of social and medical items: e.g., drug use, contraceptive technique used before pregnancy, exposure to possibly deleterious factors in the environment. The study, compared with a similar study made ten years earlier in Sweden, showed little or no difference in the use of iron and/or vitamin preparations, analgesic drugs, antibiotics, or endocrine drugs; but a drastic reduction is noted in the use of psychotropic drugs and of antihistaminic drugs. A marked decrease in frequency of first trimester X-ray exposures can be found, but no marked changes in smoking habits. Appr. 18% of the women used contraceptive pills within 6 months of becoming pregnant---3 had used them during early pregnancy. About 4% (18 women) had used IUD---one became pregnant with a Cu-UID (intra-uterine device inpregnated with copper).This type of study can provide some information on the prevalence of relatively common factors, but it must be considerably extended in order to permit an analysis of rare events, e.g., use of most drugs.

Abnormalities, Drug-Induced↗
PubMed2026

Short-Term Success, Long-Term Failure: Strain Turnover and Virulence Re-Emergence May Drive Relapse in Pouchitis.

BACKGROUND & AIMS: Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. METHODS: Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. RESULTS: Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 &#x3bc;g/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. CONCLUSIONS: Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.

Inflammatory bowel disease↗
PubMed2026

Manipulation of rhizosphere microbiome by Microbacterium sp. GB16_1_BI to promote plant growth.

AIM: The bioinoculant properties of a newly identified ammonium-releasing novel strain of Actinomycetota-Microbacterium bengalense sp. nov. GB16_1_BI (Accession number: SRX9280401) on the microbiome structure of rice rhizosphere were assessed. METHODS AND RESULT: GB16_1_BI may inhibit most bacteria present in the rice rhizosphere as well as encouraged the growth of rare bacteria specific to the waterlogged rice rhizosphere. The genome sequence as well as untargeted metabolome analyses of GB16_1_BI showed abundance of secondary metabolites with probable antimicrobial activity. Amplicon sequencing of the 16S rRNA V3-V4 region from the rhizosphere of the black rice showed inhibition of most bacteria by GB16_1_BI. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis showed increased abundance in the marker genes for nitrogen cycling (nifH, nrfA, and&#xa0;nrt) but not for nifD or nifK, which was also reflected in the ANOSIM analysis in the OTUs of the N-fixing bacteria. Higher abundance of the nitrogen-fixing methanotrophs, Methylosinus and Methylocystis in inoculated plants also led to study of the marker genes for methane metabolism. CONCLUSION: Microbes present in the rhizosphere contribute to the biogeochemical cycle by transforming unavailable minerals and by retaining nutrients for their growth, which get released after death for plant adsorption. However, not all microbes contribute positively to plant growth. Microbes compete with plants for nutrients, cause disease, or produce harmful greenhouse gases. Hence, GB16_1_BI could influence plant growth predominantly by suppressing microbes and encouraged niche-specific microbes specifically involved in nitrogen cycling.

Rhizosphere↗
PubMed1979

Immunologic dysfunction among PBB-exposed Michigan dairy farmers.

In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers ("null cells"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition.

Accidents↗
PubMed1975

Reduction of aflatoxin effects of quail.

A natural occuring outbreak of aflatoxicosis was observed in Bobwhite quail chicks while on a brooding experiment. A slight reduction in effects was noted for birds which received Tylan in the water from 0-3 days and Terramycin from 0-35 days of age. No symptoms of aflatoxicosis were observed in birds which received a product (FloxAid) containing two antibiotics and eight vitamins from 0-14 days. It is postulated that the primary mode of protection was via the water soluble vitamin D content of the product with possibly some protection from vitamins A, E and K.

Aflatoxins↗