THERAPEUTIC USE OF RESVERATROL IN THE TREATMENT OF NEUROLOGICAL AND ENDOCRINOLOGICAL PATIENTS.
The article represents the data characterizing the use of resveratrol in the treatment of various diseases, including endocrinological and neurological. It was shown that resveratrol is widely used in the treatment of various diseases due to its ability to actively suppress the inflammatory process. At the same time, in autoimmune diseases resveratrol inhibits the function of the entire population of T-cells, but when it comes to the neoplastic process, it only inhibits the activity of a subpopulation of T-cells (Treg). Thus, resveratrol can be recommended in the treatment of any diseases associated with the activation of the T-cell immunity.


Intraspecific variation in the use of water sources by the circum-Mediterranean conifer Pinus halepensis.
The relevance of interspecific variation in the use of plant water sources has been recognized in drought-prone environments. By contrast, the characterization of intraspecific differences in water uptake patterns remains elusive, although preferential access to particular soil layers may be an important adaptive response for species along aridity gradients. Stable water isotopes were analysed in soil and xylem samples of 56 populations of the drought-avoidant conifer Pinus halepensis grown in a common garden test. We found that most populations reverted to deep soil layers as the main plant water source during seasonal summer droughts. More specifically, we detected a clear geographical differentiation among populations in water uptake patterns even under relatively mild drought conditions (early autumn), with populations originating from more arid regions taking up more water from deep soil layers. However, the preferential access to deep soil water was largely independent of aboveground growth. Our findings highlight the high plasticity and adaptive relevance of the differential access to soil water pools among Aleppo pine populations. The observed ecotypic patterns point to the adaptive relevance of resource investment in deep roots as a strategy towards securing a source of water in dry environments for P. halepensis.


Structure and expression during development of Drosophila melanogaster gene for DNA polymerase alpha.
The Drosophila melanogaster gene and cDNA which span the entire open reading frame for DNA polymerase alpha, were cloned, and their nucleotide sequences were determined. The gene consists of 6 exons separated by 5 short introns. The major transcription initiation site was localized 85 bp upstream from the initiation codon. The nucleotide sequence of the open reading frame revealed a polypeptide of 1,505 amino acid residues with a molecular weight of 170,796. The amino acid sequence of the polypeptide was 37% homologous with that of the catalytic subunit of human DNA polymerase alpha. This sequence contains six regions, the orders and amino acid sequences of which are highly conserved among a number of other viral and eukaryotic DNA polymerases. We found 7 amino acid residues in the region between the 639th and 758th positions, identical to those essential for the active site of Escherichia coli DNA polymerase I-associated 3'----5' exonuclease. Thus, the exonuclease activity may be associated with Drosophila DNA polymerase alpha. Levels of the DNA polymerase alpha mRNA were high in unfertilized eggs and early embryos, relatively high in adult female flies and second-instar larva, and low in bodies at other stages of development. This feature of the expression is similar to that of the proliferating cell nuclear antigen (an auxiliary protein of DNA polymerase delta) and seems to coincide with the proportions of proliferating cells in various developmental stages. As the half life of the mRNA for DNA polymerase alpha in cultured Drosophila Kc cells was 15 min, expression of the DNA polymerase alpha gene is probably strictly regulated at the step of transcription.


Therapeutic insulin and hepatic glucose-6-phosphatase activity in preterm infants.
Hepatic glucose-6-phosphatase activity is low at birth, and in term infants rises rapidly to adult levels. In contrast, in most preterm infants, it remains low postnatally making them vulnerable to repeated hypoglycaemic episodes, resultant cerebral damage, or risk of sudden and unexpected death. To investigate the clinical features of preterm infants with low glucose-6-phosphatase enzyme activity to determine the influencing factors. Clinical data from 36 preterm infants were correlated by stepwise multiple regression analysis with V(max) of hepatic glucose-6-phosphatase as the dependent variable. The most significant correlation was with the administration of insulin (units/kg/h postnatal life) with lesser effects of respiratory distress syndrome and dopamine administration. The V(max) changes reflected changes in the level of expression of the glucose-6-phosphatase protein. In a variety of animal models, hepatic glucose-6-phosphatase levels have been shown to decrease in response to insulin, which also decreases transcription of the glucose-6-phosphatase gene. The association of insulin administration with high levels of hepatic glucose-6-phosphatase activity and protein expression was therefore most unexpected. Results from model systems, or adults, must be extrapolated to the metabolism of preterm infants with caution.


No, some types of nonconvulsive status epilepticus cause little permanent neurologic sequelae (or: "the cure may be worse than the disease").
Nonconvulsive status epilepticus (NCSE) is characterized by a cognitive or behavioral change which lasts for at least 30 minutes, with EEG evidence of seizures. Although there is little argument that generalized nonconvulsive status epilepticus (GNSE) does not cause lasting deficits, there is still debate regarding the morbidity of complex partial status epilepticus (CPSE). Because the EEG is used for diagnosis, a strong argument can be made that NCSE is significantly under-recognized and diagnosed. Furthermore, since the documented cases of permanent neurologic sequelae are few, the potential permanent morbidity from CPSE may be significantly exaggerated. The literature indicates that comatose patients have a poor prognosis largely as a result of comorbid conditions and coma, whereas lightly obtunded or slightly confused patients with NCSE have little or no sequelae. Patients with NCSE may suffer (hypotension and respiratory suppression) from iatrogenic 'aggressive' treatment with intravenous anti-epileptic drugs (IV-AEDs), and the findings in the literature indicate that subjects treated with benzodiazepines may have a worse prognosis. The clinician must balance the potential but rare neurologic morbidity associated with NCSE against the not infrequent morbidity caused by IV-AEDs. Better stratification of the level of consciousness and comorbid conditions is needed when evaluating outcomes so as to clearly distinguish among the deficits due to: comorbid conditions; the effects of treatment and the effects of status epilepticus (SE) proper.


The Effects of Low-Load Squat Jump and Maximal Isometric Priming Exercise on Muscular Performance and Perceptual State.
Harrison, PW, James, LP, Jenkins, DG, McGuigan, MR, Holmberg, PM, and Kelly, VG. The effects of low-load squat jump and maximal isometric priming exercise on muscular performance and perceptual state. J Strength Cond Res 38(1): 1-9, 2024-The aim of this study was to examine responses at 3 and 27 hours after low-load jump squat (LL) and maximal isometric half-squat (ISO) priming stimuli. Fifteen resistance-trained males performed LL (4 × 3 at 20% 1 repetition maximum [1RM]), ISO (4 × 3 seconds), and control (CON) activities (standardized warm-up) in a randomized and counterbalanced order. Countermovement jump (CMJ) and isometric midthigh pull tests were conducted to assess performance changes after priming and CON activities. No clear changes in CMJ measures were found after priming activities compared with CON. However, small effect size improvements were found after priming stimuli completed on the same day. A 2.9% decrease in concentric phase duration (CI = 0.3-5.9, p = 0.333, Cliff's delta = -0.156) and a 9.1% increase in RSImod (CI = 0.2-12.3, p = 0.151, Cliff's delta = -0.218) occurred at 3 hours after LL compared with CON. Braking phase duration (CI = 0.8-10.6, p = 0.333, Cliff's delta = -0.213) was 2.9% shorter at 3 hours after ISO compared with CON. No clear changes in isometric peak force occurred after priming activities compared with CON. Additionally, questionnaires were completed to assess perceptual state and perceived effectiveness of the priming stimulus to influence performance. An increase in the "effect of activity" was perceived at 3 hours after LL and ISO (p = 0.013-0.044, Cliff's delta = 0.578-0.6) and at 27 hours after ISO (p = 0.99, Cliff's delta = 0.173) compared with CON. An increase in "muscular heaviness" was also reported at 3 hours after ISO compared with CON (p = 0.199, Cliff's delta = 0.320). The collective findings suggest limited benefits over the day after LL and ISO priming stimuli. However, as there was substantial variation in individual responses, the relative nature of priming responses should be considered when prescribing similar strategies in practical environments.


Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis.
Allergic rhinitis is a common condition often requiring treatment. We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant humanized construct of a murine antibody that binds to circulating IgE, could control symptoms and reduce intake of concomitant medication in seasonal allergic rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule predicted to reduce serum free IgE levels below 25 ng/mL. We randomly assigned 251 adult subjects with a history of SAR and a positive skin test response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 times during the season, depending on baseline IgE levels. The primary efficacy variable was the subject's average daily nasal symptom severity score (sneezing, itching, runny, and stuffy nose) from diary data collected over the double-blind treatment period. Secondary efficacy variables included the average number of rescue antihistamine tablets per day, the proportion of days with any SAR medication use, and rhinoconjunctivitis-specific quality of life (QOL). Significant between-treatment differences in favor of rhumAb-E25 were observed in average daily nasal symptom severity scores, the average number of tablets of rescue antihistamines per day, the proportion of days with any SAR medication use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb-E25-treated subjects and were associated with clinical effectiveness. Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were detected. Compared with placebo, rhumAb-E25 was safe and effective in controlling birch pollen-induced SAR symptoms, with less concomitant medication use and improved QOL. This study shows the therapeutic potential of anti-IgE antibody in SAR.


Cirrhotic ascites. Pathophysiology, diagnosis, and management.
Cirrhotic ascites occurs via both overflow and underfill mechanisms. Intrahepatic hypertension activates a hepatic baroreceptor reflex that enhances renal sodium absorption; plasma volume is expanded. As cirrhosis progresses, the hepatoportal Starling forces become sufficiently disturbed to sequester this "overflow" in the peritoneal cavity, which results in ascites formation. "Underfill" of the vascular system occurs and eventually dominates the clinical picture. Finally, intrahepatic hypertension also activates the renin-angiotensin system, which causes renal vasoconstriction; the increase in renal prostaglandin synthesis maintains renal blood flow. Although cirrhotic ascites is traditionally classified as a transudate, the serum-ascites albumin gradient may be a better indicator of ascites secondary to portal hypertension than other causes. General management of patients with cirrhotic ascites includes severe restriction of dietary sodium intake and bed rest; diuretics are added if spontaneous diuresis does not occur after 3 to 4 days.


Frailty and Its Contributory Factors in Older Adults: A Comparison of Two Asian Regions (Hong Kong and Taiwan).
This study aimed to compare the prevalence of frailty across three Chinese populations: Hong Kong, Taiwan-urban and Taiwan-rural. Contributing factors to disparities in frailty were also examined. Data were derived from the Osteoporotic Fractures in Men (MrOs) and Women (MsOs) (Hong Kong) Study (n = 4000) and the Taiwan Longitudinal Study on Aging (n = 2392). Frailty was defined as an index calculated from 30 multiple deficits. The ratio of the frailty index to life expectancy at birth (FI/LE) was used as an indicator of compression of morbidity. Frailty was more prevalent in Taiwan-urban (33.1%) and Taiwan-rural (38.1%) compared to Hong Kong (16.6%, p < 0.05) and was higher in women (22.6-49.7%) than in men (10.5-27.5%, p < 0.05). The ratios of FI/LE were higher in Taiwan-urban and Taiwan-rural (both 0.27) compared to Hong Kong (0.20, p < 0.05). Multivariate analyses revealed that older age, being a woman and low levels of physical activity were common risk factors for frailty across the three populations. Alcohol use was inversely associated with frailty in both Hong Kong and Taiwan-urban populations, but not in Taiwan-rural. Living alone was associated with frailty in Hong Kong men, but not in Hong Kong women or Taiwanese people. For all study populations, older age and being a woman constituted the highest attributable factor. This comparison provides useful data to inform government policies.


Supporting bereaved parents: practical steps in providing compassionate perinatal and neonatal end-of-life care. A North American perspective.
Providing compassionate bereavement support challenges care-givers in perinatal medicine. A practical and consistent approach tailored to individual families may increase the care-giver's ability to relieve parental grief. This approach includes: (1) clear and consistent communication compassionately delivered; (2) shared decision-making; (3) physical and emotional support; and (4) follow-up medical, psychological and social care. Challenges to providing comprehensive end-of-life care include care-giver comfort, consistency of care, cultural and legal barriers, and lack of adequate training.


Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium. Immunoelectron microscopic and electron microscopic morphometric analysis.
Pathologic changes in the basement membrane (BM) of postcapillary venules (PCV) and capillaries in rheumatoid arthritis (RA) synovium were studied by immunoelectron microscopy, using a monoclonal antibody against human type IV collagen, C(IV)22, and by electron microscopic morphometric analysis. The sublining region of RA synovium was classified into lymphocyte-rich areas, transitional areas, and interstitial areas, according to their pattern of cellular infiltration. In lymphocyte-rich areas, the BM of the PCV and capillaries were minimally thickened; disruption of the lamina densa was seldom seen. Transitional areas, which contained macrophages, lymphocytes, and plasma cells, had numerous PCV and capillaries. The BM was markedly thickened and partially multilamellated, and there were many disruptions in the lamina densa. The BM contained degenerated endothelial cells and cell debris. On immunostaining of this BM with monoclonal antibody C(IV)22, type IV collagen stained heavily, mainly in the disrupted lamina densa; this indicates that the thickening was, at least in part, the result of an increase in BM collagen. In uninfiltrated interstitial areas, BM were moderately thickened and multilamellated, and showed few disruptions of the lamina densa; there were similar increases in type IV collagen, but cell debris was seldom observed. Measurement of the BM width, the ratio of BM width to vessel diameter, and the fraction of vascular cross-sectional area occupied by BM demonstrated that the thickness of the BM of both PCV and capillaries was greatest in transitional areas and was smallest in lymphocyte-rich areas (P less than 0.01). Since macrophages and macrophage-derived factors have been found to promote synthesis of BM collagen type IV, and since transitional and interstitial areas are rich in macrophages and histiocytes, respectively, it is suggested that these mononuclear cells and the factors secreted by them play a significant role in the thickening of the BM of PCV and capillaries in RA synovitis.


Is the major Drosophila heat shock protein present in cells that have not been heat shocked?
When eukaryotic cells are exposed to elevated temperatures they respond by vigorously synthesizing a small group of proteins called the heat shock proteins. An essential element in defining the role of these proteins is determining whether they are unique to a stressed state or are also found in healthy, rapidly growing cells at normal temperatures. To date, there have been conflicting reports concerning the major heat-induced protein of Drosophila cells, HSP 70. We report the development of monoclonal antibodies specific for this protein. These antibodies were used to assay HSP 70 in cells incubated under different culture conditions. The protein was detectable in cells maintained at normal temperatures, but only when immunological techniques were pushed to the limits of their sensitivity. To test for the possibility that these cells contain a reservoir of protein in a cryptic antigenic state (i.e., waiting posttranslational modification for use at high temperature), we treated cells with cycloheximide or actinomycin D immediately before heat shock. HSP 70 was not detected in these cells. Finally, we tested for the presence of a reservoir of inactive messages by using a high stringency hybridization of 32P-labeled cloned gene sequences to electrophoretically separated RNAs. Although HSP 70 mRNA was detectable in rapidly growing cells, it was present at less than 1/1,000th the level achieved after induction.


Improving access to health care for uninsured elderly patients.
The purpose of this article is to explore the barriers that the uninsured elderly population encounter when accessing health care in the United States. These barriers include, but are not limited to lack of transportation, insurance, or family support; the daunting complexity of the health care system; poverty; culture; poor patient-health care provider communications; race/ethnicity; and lack of health care professionals such as nurses and doctors with adequate geriatric preparation, or generalists who are undereducated in geriatrics. The number of health care professionals currently available to treat elderly persons in the United States is inadequate. The Federal government should take steps to develop solutions to improve access to health care and decrease health disparities for older adults. As a nation, we should be proactive in addressing these concerns instead of waiting for new barriers to arise that further limit access to health care for elderly patients and their families. In this article, we provide an assessment of the barriers that limit access to health care in the uninsured elderly population and suggest recommendations and possible solutions to eliminate or reduce these barriers.


Blood collection and transfusion in the United States in 2001.
Collection, processing, and transfusion of blood and blood components in the United States in 2001 were measured and compared with prior years. The survey was completed by 1443 blood centers and hospitals. Statistical procedures were used to verify the representativeness of the sample and to estimate national totals. The total US blood supply in 2001 was 15,320,000 units (before testing), 10.4 percent greater than in 1999. It included 14,259,000 allogeneic units, 619,000 autologous units, and 273,000 red cell (RBC) units collected by apheresis. Transfusion of whole blood (WB) and RBCs increased by 12.2 percent to 13,898,000 units. Platelet (PLT) transfusions totaled 10,196,000 units, an increase of 12.6 percent in comparison with 1999. The use of single-donor apheresis PLTs increased by 26.0 percent to 7,582,000 PLT concentrate equivalent units. The use of PLTs from WB (PLT concentrates) continued a downtrend, declining 13.9 percent to 2,614,000. The margin between transfusion demand and the total allogeneic supply in 2001 was 1,162,000 units, 7.9 percent of supply. By comparison, the 1999 margin was 9.1 percent. The rate of blood collection per 1,000 donor-eligible population in 2001 was 8.9 percent higher than in 1999, due largely to additional donations following the September terrorist attacks. During the same period, however, the rate of transfusion per 1,000 total US population increased by 9.9 percent to 50.0 units, the highest in 15 years of measurement. The steady increase in demand continues to challenge the US blood community.


Comparative population structure of Plasmodium falciparum circumsporozoite protein NANP repeat lengths in Lilongwe, Malawi.
Humoral immunity to Plasmodium falciparum circumsporozoite protein is partly mediated by a polymorphic NANP tetra-amino acid repeat. Antibody response to these repeats is the best correlate of protective immunity to the RTS,S malaria vaccine, but few descriptions of the natural variation of these repeats exist. Using capillary electrophoresis to determine the distribution of NANP repeat size polymorphisms among 98 isolates from Lilongwe, Malawi, we characterised the diversity of P. falciparum infection by several ecological indices. Infection by multiple distinct variants was common, and 20 distinct repeat sizes were identified. Diversity of P. falciparum appeared greater in children (18 variants) than adults (12 variants). There was evidence of genetic distance between different geographic regions by Nei's Standard Genetic Distance, suggesting parasite populations vary locally. We show that P. falciparum is very diverse with respect to NANP repeat length even on a local level and that diversity appears higher in children.


Revisiting the call to care: an ethical perspective.
As the 21st century rapidly approaches, a reexamination of nursing's call to care is timely. Caring, long claimed as central to nursing practice, seems to be in jeopardy. The article presents evidence that nurses do care for their patients. Moreover, caring is essential to the moral integrity of their practice. The article calls on nurses to put patients before convenience and to remember that without patients there would be no profession.


Predictors of recurrence of ovarian granulosa cell tumors.
The prognosis of granulosa cell tumors (GCTs) is overall favorable, but a proportion of patients will experience recurrence. We report one of the largest series of patients with GCT for whom clinical, morphologic, and immunohistochemical markers have been assessed for their roles as predictors of recurrence. Patients with the diagnosis of GCT were identified at 2 hospitals from 1974 to 2004; a detailed chart analysis was performed. Tissue blocks were analyzed immunohistochemically for mitotic index, luteinization, inhibin staining, epidermal growth factor receptor, and Ki67 expression. Univariate and multivariate analyses were performed. Sixty-seven patients were identified. Follow-up data up to 30 years were available. The mean age at diagnosis was 48.1 years. Twenty-five patients experienced recurrence. A statistically significant correlation (P < 0.05) was observed for age at diagnosis, with earlier age being an adverse factor (43.6 vs 50.9, P < 0.01), and use of adjuvant chemotherapy postoperatively (24% vs 40% in the nonrecurrence group). Luteinization and the immunohistochemical markers, such as inhibin, Ki67, and epidermal growth factor receptor, seemed to significantly increase the risk of recurrence if expressed. A multivariate analysis model confirmed that younger age at diagnosis and higher expression of inhibin and Ki67 are significant risk factors of GCT recurrence. Identification of patients who are at a high risk for recurrence of GCT is critical. Routine treatment for all patients with cytotoxic chemotherapy is not justified. We report a set of predictors of recurrence for GCT that identified subsets of patients who may benefit from prolonged surveillance and/or adjuvant systemic chemotherapy.


Long-term alteration of the hypothalamic-pituitary-adrenal axis in children undergoing cardiac surgery in the first 6 months of life.
Children with congenital heart disease (CHD) have poorer neurodevelopmental and psychological outcomes. The mechanisms underlying this remain unclear. One mechanism could be that the stressful experience of cardiac surgery early in life influences long-term hypothalamic-pituitary-adrenal (HPA) axis regulation. Dysregulation of the HPA axis has been linked to poorer neurocognitive and psychological outcomes in other study populations. This case-control study aims to compare HPA-axis regulation (circadian rhythm and reactivity) using salivary cortisol in 3- to 5-year-olds with CHD who did and did not have cardiac surgery prior to 6 months of age. Saliva samples for cortisol analysis were collected from preschoolers with CHD (N = 28, Males = 18, Females = 10) over two weekend days, and before and after an echocardiogram. Caregiver education, child age, sex, and cardiac disease severity score were included as confounders. Multilevel analysis (hierarchical linear modeling) was used to analyze the data. The analysis for the cortisol circadian rhythm shows that the early surgery group has a flatter diurnal slope secondary to lower mean weekend morning waking cortisol levels than controls but similar mean bed time values. Multilevel analysis of the stress response to an echocardiogram indicates that the early surgery group has an increased response when compared to the control group. This is the first study to show that cardiac surgery prior to 6 months of age is associated with a different pattern of HPA-axis regulation at 3-5 years of age.


Synthesis of small heat-shock proteins is part of the developmental program of late seed maturation.
Small heat-shock proteins (sHSPs) accumulate in plants in response to high-temperature stress. Specific sHSPs, the cytosolic class I and class II proteins, are also expressed in the absence of stress in maturing seeds of several species, and a role for these proteins in desiccation tolerance, dormancy, or germination has been hypothesized. We demonstrate that class I sHSPs are expressed during Arabidopsis seed development in a pattern similar to that previously observed in other species: they are first detected during mid-maturation, are most abundant in dry seeds, and decline rapidly during germination. Although the class I sHSP family in Arabidopsis appears to consist of four genes, expression of a single gene, Athsp 17.4, accounts for the majority of sHSPs in maturing seeds. sHSP levels were also examined in seeds of several Arabidopsis mutants with reduced sensitivity to abscisic acid inhibition, including aba1, abi1, and abi2, abi3-1, abi3-6, abi4, and abi5-1. The abi3-1 mutant has 10-fold reduced levels of sHSPs; sHSPs are undetectable in the abi3-6 mutant. All other mutants were indistinguishable from wild type. These results suggest that sHSP expression in seeds is regulated by the ABI3 response pathway and wild-type levels of sHSPs are not sufficient for seed dormancy and not necessary for desiccation tolerance. However, roles in either process cannot be ruled out. In total the data indicate that the expression of sHSPs in seeds is part of the normal developmental program of late seed maturation and the presence of sHSPs has adaptive significance for plant reproduction.


A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.
There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment (P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients (P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses.


Acute myocardial infarction (MI), the most severe complication of coronary artery disease, develops in 2-4% of patients with various malignancies. to explore the specific properties of ST-segment elevation myocardial infarction (STEMI) course in patients with cancer and its effect on short-term outcome. We included in this study 45 patients with STEMI and history of cancer hospitalized in the period from 01.01.2015 to 01.01.2017 (group I; 58% men, mean age 69.07±11.60 years). In the comparison group (group II) we selected 90 age and gender matched persons (58% men, mean age 68.16±11.75 years) from patients with STEMI without oncological diseases. There were no differences between groups in main risk factors of cardiovascular diseases, except greater proportion of patients with damage of peripheral arteries in group 1 (22.2% compared with 5.6% in group 2, p=0.025). There were also no differences between groups in clinical characteristics at admission. However values of the following parameters were significantly lower in group I: concentration of hemoglobin (115.56±23.07 vs. 133.70±16.45 g/l in group 2, р<0.001), red blood cell count (3.95±0.66x1012/l vs. 5.57±0.72x1012/l in group 2, р<0.001), platelets (93±0.97x109/l vs 186±18.3x109/l in group 2, p<0.001), total cholesterol (4.12±2.17 vs. 6.24±2.56 mmol/L in group 2, р<0.001). There were differences in the frequency of use of antiplatelet drugs: at prehospital stage acetylsalicylic acid was given to 48.9% and 77.8% of patients in groups 1 and 2, respectively (p=0.044); clopidogrel and ticagrelor were also significantly more rarely used in group 1. There was no difference in use of thrombolysis and percutaneous coronary interventions (4.4 and 53.3% vs 5.6 and 56.6% in groups 1 and 2, respectively). In group 2 greater portion of patients was given statins (68.9 vs. 77.8%, p=0.021) and angiotensin-converting enzyme inhibitors (55.6 vs. 82.2%, p=0.008). Inhospital mortality was the same in both groups (4.4%). Occurrence of complications (bleeding, pulmonary edema, cardiogenic shock), and frequency of use of intra-aortic balloon counterpulsation, temporary cardiac pacing were similar. However in group 1 greater portion of patients had ventricular tachyarrhythmias (15.6 vs 2.2% in group 2, р=0.007); the presence of cancer was the only independent predictor of their emergence in multiple logistic regression (OR 8.11 [1.11-40.83], p=0.011). Rates of application of myocardial reperfusion in STEMI patients with and without history of cancer were the same. Despite similar hospital mortality revealed peculiarities of STEMI course could affect long-term outcomes. Confirmation of this hypothesis requires planned prospective studies.


Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity.
The neural crest gives rise to three major adrenergic cell types: sympathetic principal neurons, adrenal chromaffin cells, and small intensely fluorescent (SIF) cells. All of these derivatives synthesize and store catecholamines, but they differ in numerous other characteristics. SIF cells appear intermediate in phenotype between the other two. We have examined the role of several environmental factors in the differentiation of sympathetic principal neurons and adrenal chromaffin cells. In previous studies of young rat adrenal chromaffin cells in dissociated cell culture, differentiated characteristics such as the presence of the enzyme phenylethanolamine N-methyltransferase (PNMT), epinephrine (E) synthesis, and large catecholamine storage vesicles were not well maintained. Here we describe long-term culture of chromaffin cells which, in the presence of micromolar glucocorticoid, maintained all of these characteristics. In addition, chromaffin cells of a variety of ages were found to be dependent on glucocorticoid for long-term survival in culture. In the absence of glucocorticoid, many adrenal chromaffin cells from neonatal rats could be rescued by nerve growth factor (NGF) administration. They extended neurites, as previously described by Unsicker and colleagues (Unsicker, K., B. Krisch, U. Otten, and H. Thoenen (1978) Proc. Natl. Acad. Sci. U.S.A. 75: 3498-3502). In contrast to previous studies, however, with long-term exposure to NGF these cells became indistinguishable from mature sympathetic neurons, as judged by the following morphological and biochemical criteria: increased cell size and loss of intense CA fluorescence in their cell bodies; acquisition of characteristic neuronal ultrastructure, including morphologically specialized synapses; loss of chromaffin granules, PNMT, and E synthesis; and acquisition of neuron markers, including tetanus toxin labeling and immunoreactivity to neurofilament protein. This conversion to neurons was markedly enhanced by addition of a non-neuronal cell conditioned medium (CM) containing a neurite-promoting factor, which acted by increasing the NGF responsiveness of the chromaffin cells. Even chromaffin cells from adult rats, which are known to grow few processes in response to NGF alone, became neuronal in the presence of this CM plus NGF. While converting to neurons, adrenal chromaffin cells transiently assumed an intermediate phenotype resembling type I SIF cells, which suggests particular developmental relationships between the different cell types of the sympathoadrenal lineage.(ABSTRACT TRUNCATED AT 400 WORDS)


The Effects of Omega-3 Fatty Acids Supplementation on Inflammatory Factors in Cancer Patients: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials.
Until now, no study evaluated the impact of optimum intake of omega-3 fatty acids on inflammatory factors. We aimed to investigate the dose-dependent effects of omega-3 fatty acids supplementation on inflammatory factors in cancer patients. PubMed, Scopus and ISI Web of Science were searched until July 2022 to find randomized controlled trials (RCTs) for examining the efficacy of omega-3 fatty acids on inflammatory factors. Our primary outcomes were interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and albumin. The results of 33 trials (2068 participants) revealed that each 1 g/day omega-3 fatty acids (oral/enteral) significantly reduced IL-6 (SMD: -1.17 pg/ml; 95% CI: -1.78, -0.55; p < 0.001; GRADE = moderate), and TNF-α (SMD: -2.15 pg/ml; 95% CI: -3.14, -1.16; p < 0.001; GRADE = very low). Moreover, each 0.5 g/kg/day omega-3 fatty acids (parenteral) significantly reduced TNF-α (SMD: -1.11 pg/ml; 95% CI: -2.02, -0.19; p = 0.017; GRADE = low). With moderate and very low evidence certainty, each 1 g/day of omega-3 fatty acids supplementation (oral/enteral) has a beneficial effect on IL-6 and TNF-α. Each 0.5 g/kg/day omega-3 fatty acids (parenteral) could also exert a favorable impact on TNF-α, but the certainty of the evidence was low.


The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both?
The gut-brain axis is the bidirectional communication between the gut and the brain, which occurs through multiple pathways that include hormonal, neural and immune mediators. The signals along this axis can originate in the gut, the brain or both, with the objective of maintaining normal gut function and appropriate behaviour. In recent years, the study of gut microbiota has become one of the most important areas in biomedical research. Attention has focused on the role of gut microbiota in determining normal gut physiology and immunity and, more recently, on its role as modulator of host behaviour ('microbiota-gut-brain axis'). We therefore review the literature on the role of gut microbiota in gut homeostasis and link it with mechanisms that could influence behaviour. We discuss the association of dysbiosis with disease, with particular focus on functional bowel disorders and their relationship to psychological stress. This is of particular interest because exposure to stressors has long been known to increase susceptibility to and severity of gastrointestinal diseases.


Costs of treating simple nosocomial urinary tract infection.
Four cost studies show that extra time spent in hospital because of nosocomial urinary tract infection ranged from 0.6 to 5 days. Extra hospital charges ranged from $146 to $558 with an average of about $355. Updated hospital costs project annual national costs of $1.8 billion.


A mathematical model of the vagally driven primary pacemaker.
Information regarding the electrical behavior of cells in the sinoatrial (SA) node of the heart is by no means complete; yet sufficiently detailed information is available in the literature to allow the formulation of a reasonably quantitative model of the membrane of the primary pacemaker cell (P-cell) and its parasympathetic innervation. In a previous study [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H207-H218, 1982], the well-known McAllister-Noble-Tsien model of the cardiac Purkinje fiber is modified to account for the electrical activity of the SA node. In the present study, the effects of vagal activity on sinus rhythm are considered by adding a special acetylcholine-sensitive "muscarinic channel" to the membrane model for the P-cell. The resulting model mimics published data quite well and is capable of characterizing the free-running SA node cell as well as its responses to electrotonic and vagal stimulation.


Behaviour of indicators of exposure and effect after cessation of occupational exposure to lead.
The behaviour of blood lead (PbB) and of some indicators of effect (erythrocyte protoporphyrin IX (EP), delta-aminolaevulinic acid dehydratase activity of erythrocytes (ALAD), and urinary delta-aminolaevulinic acid (ALAU)) were studied in subjects who had ceased working with inorganic lead for at least one year. Relations between these indices and chelatable lead (PbU-EDTA (lead in urine after injection of CaNa2 EDTA 1 g intravenously)), a test that is used to evaluate the lead deposits in the body, were also analysed. As a comparison, a group of subjects currently exposed was studied. In the workers with past exposure the PbB values were significantly lower, at the same PbU-EDTA levels, than those found in subjects at work. The relation between EP and PbU-EDTA shows that, corresponding levels of chelatable lead, the values of the erythrocyte metabolite are identical in the two groups. Considering the EP-PbB relation, however, at the same PbB levels the protoporphyrin values appear distinctly more altered in the subjects with past exposure. Similar results were obtained from a study of the relations between ALAD and PbU-EDTA and between ALAD and PbB. The relation between ALAU and PbU-EDTA, however, shows that, at the same PbU-EDTA levels the urinary metabolic in past-exposed subjects is distinctly lower than in subjects at work, while the relation between ALAU and PbB shows that, for similar blood lead values, the ALAU levels are identical. On the basis of the results obtained it is concluded that in subjects with past exposure, EP and ALAD can be used in establishing the persistence and extent of an "active deposit" of lead in the organism, while PbB is of very limited use.


in vivo ischemia monitoring array for endoscopic surgery.
An array with all-solid-state, potentiometric, miniaturized sensors for pH and potassium was developed to be introduced into the stomach or other sectors of the digestive tract by means of flexible endoscopy. These sensors perform continuous and simultaneous measurement of extracellular pH and potassium. This detection seeks to sense ischemia in the gastric mucosa inside the stomach, an event indicative of local microvascular perfusion and tissue oxygenation status. Our array is proposed as a medical tool to identify the occurrence of the ischemia after gastrointestinal or gastroesophageal anastomosis. The stability and feasibility of the miniaturized working and reference electrodes integrated in the array were studied under in vitro conditions, and the behavior of the potassium and pH ion-selective membranes were optimized to work under acidic gastric conditions with high concentrations of HCl. The array was tested in vivo in pigs to measure the ischemia produced by clamping the blood flow into the stomach. Our results indicate that ischemic and reperfusion states can be sensed in vivo and that information on tissue damage can be collected by this sensor array. The device described here provides a miniaturized, inexpensive, and mass producible sensor array for detecting local ischemia caused by unfavorable anastomotic perfusion and will thus contribute to preventing anastomotic leakage and failure caused by tissue necrosis.


Multiple facets of TPP1 in telomere maintenance.
Telomeres are nucleoprotein complexes that cap the ends of all linear chromosomes and function to prevent aberrant repair and end-to-end chromosome fusions. In somatic cells, telomere shortening is a natural part of the aging process as it occurs with each round of cell division. In germ and stem cells, however, the enzyme telomerase synthesizes telomere DNA to counter-balance telomere shortening and help maintain cellular proliferation. Of the primary telomere end-binding proteins, TPP1 has recently emerged as a primary contributor in protecting telomere DNA and in recruiting telomerase to the telomere ends. In this review, we summarize the current knowledge regarding the role of TPP1 in telomere maintenance.


A triple entente: virus, neurons, and CD8+ T cells maintain HSV-1 latency.
Herpes simplex virus type 1 (HSV-1) travels by retrograde transport to sensory ganglia where latency is established. Recurrent disease results from virus reactivation and anterograde transport to nerve termini. Prevention of reactivation requires a complex interplay among virus, neuron, and immune response. Study of this tripartite relationship suggests possible interaction, and even communication among these components, that direct an immune response that allows for control of virus while preserving the viability of host tissue. Exciting new evidence supports the view that CD8+ effector T cells employ both lytic granule-dependent and interferon gamma-dependent effector mechanisms in maintaining HSV-1 latency.


Gender differences of low-dose aspirin-associated gastroduodenal ulcer in Japanese patients.
To clarify the gender differences about the clinical features and risk factors of low-dose aspirin (LDA) (81-100 mg daily)-associated peptic ulcer in Japanese patients. There were 453 patients under treatment with LDA (298 males, 155 females) who underwent esophagogastroduodenoscopy at the Department of Gastroenterology and Hepatology of Hiratsuka City Hospital between January 2003 and December 2007. They had kept taking the LDA or started treatment during the study period and kept taking LDA during the whole period of observation. Of these, 119 patients (87 males, 32 females) were diagnosed as having LDA-associated peptic ulcer. We examined the clinical factors associated with LDA-associated peptic ulcer in both sexes. A history of peptic ulcer was found to be the risk factor for LDA-associated peptic ulcer common to both sexes. In female patients, age greater than 70 years (prevalence ORs 8.441, 95% CI: 1.797-33.649, P = 0.0069) was found to be another significant risk factor, and the time to diagnosis as having LDA-associated peptic ulcer by endoscopy was significantly shorter than that in the male patients (P = 0.0050). We demonstrated gender differences about the clinical features and risk factors of LDA-associated peptic ulcer. Special attention should be paid to aged female patients taking LDA.


Prostate specific antigen predicts the long-term risk of prostate enlargement: results from the Baltimore Longitudinal Study of Aging.
Prostate specific antigen (PSA) is a predictor of prostate growth in men with lower urinary tract symptoms. The long-term risk of prostate enlargement as a function of PSA among community dwelling volunteers is unknown. A Cox proportional hazards regression model was used to study the relationship between baseline PSA level at ages 40 to 49.9 years in 194 men, 50 to 59.9 in 191 and 60 to 69.9 in 144, and prostate enlargement, defined as a prostate volume larger than the 75th percentile for age decade, as measured by magnetic resonance imaging in a longitudinal study of aging (Baltimore Longitudinal Study of Aging, National Institute on Aging). Kaplan-Meier survival analysis was performed to estimate the probability of freedom from prostate enlargement with time as a function of baseline PSA level. The relative risk of prostate enlargement was 3- to 6-fold higher for men 40 to 49.9 years old with a baseline PSA of 0.31 ng./ml. or more compared to men with PSA levels of 0.30 ng./ml. or less at baseline. The relative risk was increased 5- to 9-fold in men 50 to 59.9 years old and 11-fold in those 60 to 69.9 years old when comparing men with PSA greater than 0.80 ng./ml. and greater than 1.70 ng./ml. with those with PSA 0.50 or less. The cumulative probability of freedom from prostate enlargement at 20 years was 0.89 (95% confidence interval ([CI] 0.79-0.99) and 0.63 (0.52-0.74) for men 40 to 49.9 years old with PSA levels below and above 0.30 ng./ml., respectively. For men 50 to 59.9 years old the 10-year probability of freedom from prostate enlargement was 0.90 (95% CI 0.84-0.96) and 0.59 (0.43-0.74) when PSA levels were below and above 0.80 ng./ml., respectively. At age 60 to 69.9 years the 10-year probability of freedom from prostate enlargement was 0.83 (95% CI 0.72-0.93) and 0.27 (0.09 to 0.48) when PSA levels were below and above 1.70 ng./ml., respectively. These data demonstrate the long-term risk of prostate enlargement by PSA level. Risk stratification based on PSA level may be useful to identify men at greatest risk for adverse events due to prostate enlargement and selection of men for future benign prostatic hyperplasia studies.


The ATLS course, a survey of 228 ATLS providers.
Advanced Trauma Life Support (ATLS) courses teach a system for the initial assessment and management of trauma patients that aims to optimise initial care and reduce mortality and morbidity, and have been adopted worldwide. This questionnaire survey characterised those who took up this particular educational resource in Scotland during a four year period after its introduction, and analysed how they felt it had affected their clinical competence. Irrespective of their previous level of training and experience, nearly all surgeons and anaesthetists who took this course felt that it had improved their clinical skills and other professional attributes. The significance of these results is discussed in the context of postgraduate surgical and anaesthetic training in Scotland.


Effects of thickness of different types of high-translucency monolithic multilayer precolored zirconia on color accuracy: An in vitro study.
High-translucency monolithic multilayer precolored zirconia provides acceptable esthetics and eliminates chipping of the veneering porcelain. However, the color is not always consistent with the standard Vita shade guide, and the color saturation may vary with the thickness of the zirconia. The purpose of this in vitro study was to characterize the effect of thickness on the color accuracy of high-translucency monolithic multilayer precolored zirconia. Plate-shaped (20×20 mm) Vita A2 shade high-translucency monolithic multilayer precolored zirconia specimens of 3 types (SHT Multilayer, AT Multilayer, and 3D Multilayer) in 4 thicknesses (0.5, 1.0, 1.5, and 2.0 mm) were fabricated (N=120, n=10). A spectrophotometer was used to measure the color attributes (CIELab) against gray or A2 substrates to evaluate the color accuracy based on differences in color (ΔE) (versus the Vita shade guide) and chroma. Statistical analysis was performed by using the Pearson correlation, 2-way ANOVA, and post hoc Scheffé test (α=.05). Against gray substrates, thickness was significantly positively correlated with all color attributes. Against A2 substrates, L∗ values increased with an increase in thickness; however, a∗, b∗, and chroma values remained stable. Zirconia with a thickness of 1.0 mm exhibited the lowest ΔE, regardless of the type, except for AT Multilayer against A2 substrates, where the lowest ΔE was achieved at 0.5 mm. At thicknesses ≥1.0 mm, the ΔE between the 2 substrates was imperceivable. Thickness affected the color accuracy of different high-translucency monolithic multilayer precolored zirconia types. It appears that the optimal thickness in terms of color accuracy is 1.0 mm. These results could be used as a reference for the selection and preparation of abutments in clinical applications.


Deciding together? Best interests and shared decision-making in paediatric intensive care.
In the western healthcare, shared decision making has become the orthodox approach to making healthcare choices as a way of promoting patient autonomy. Despite the fact that the autonomy paradigm is poorly suited to paediatric decision making, such an approach is enshrined in English common law. When reaching moral decisions, for instance when it is unclear whether treatment or non-treatment will serve a child's best interests, shared decision making is particularly questionable because agreement does not ensure moral validity. With reference to current common law and focusing on intensive care practice, this paper investigates what claims shared decision making may have to legitimacy in a paediatric intensive care setting. Drawing on key texts, I suggest these identify advantages to parents and clinicians but not to the child who is the subject of the decision. Without evidence that shared decision making increases the quality of the decision that is being made, it appears that a focus on the shared nature of a decision does not cohere with the principle that the best interests of the child should remain paramount. In the face of significant pressures toward the displacement of the child's interests in a shared decision, advantages of a shared decision to decisional quality require elucidation. Although a number of arguments of this nature may have potential, should no such advantages be demonstrable we have cause to revise our commitment to either shared decision making or the paramountcy of the child in these circumstances.


Bioinformatics analysis of circulating miRNAs related to cancer following spinal cord injury.
Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes (TP53, CCND1 and KRAS) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.


An Attempt to Induce Transient Immunosuppression Pre-erythrocytapheresis in a Girl With Sickle Cell Disease, a History of Severe Delayed Hemolytic Transfusion Reactions and Need for Hip Prosthesis.
We report on a case of delayed hemolytic transfusion reaction (DHTR) occurred 7 days after an erythrocytapheresis or eritroexchange procedure (EEX) treated with rituximab and glucocorticoids in a 15-years old patient with sickle cell disease. EEX was performed despite a previous diagnosis of alloimmunization, in order to reduce hemoglobin S rate before a major surgery for avascular necrosis of the femoral head. A first dose of rituximab was administered before EEX. However, rituximab couldn't prevent DHTR that occurred with acute hemolysis, hemoglobinuria and hyperbilirubinemia. A further dose of rituximab and three boli of methylprednisolone were given after the onset of the reaction. It is likely that the combined use of rituximab and steroids managed to gradually improve both patient's general conditions and hemoglobin levels. Nor early or late side effects were registered in a 33-months follow-up period. This report suggests the potential effectiveness and safety of rituximab in combination with steroids in managing and mitigating the symptoms of delayed post-transfusional hemolytic reactions in alloimmunized patients affected by sickle cell disease with absolute need for erythrocytapheresis.


Impact of fitness versus obesity on routinely measured cardiometabolic risk in young, healthy adults.
Obesity demonstrates a direct relation with cardiovascular risk and all-cause mortality, while cardiorespiratory fitness demonstrates an inverse relation. In clinical practice, several cardiometabolic (CM) risk factors are commonly measured to gauge cardiovascular risk, but the interaction between fitness and obesity with regard to CM risk has not been fully explored. In this study, 2,634 Brazilian adults referred for employer-sponsored heath exams were assessed. Obesity was defined as body mass index >30 kg/m(2) or waist circumference >102 cm in men or >88 cm in women when body mass index was 25 to 30 kg/m(2). Fitness was quantified by stage achieved on an Ellestad treadmill stress test, with those completing stage 4 considered fit. Hepatic steatosis was determined by ultrasound. CM risk factors were compared after stratifying patients into 4 groups: fit and normal weight, fit and obese, unfit and normal weight, and unfit and obese. Approximately 22% of patients were obese; 12% were unfit. Fitness and obesity were moderately correlated (ρ = 0.38 to 0.50). The sample included 6.5% unfit and normal-weight subjects and 16% fit and obese subjects. In overweight and obese patients, fitness was negatively associated with CM risk (p <0.01 for all values). In fit patients, increasing body mass index was positively associated with CM risk (p <0.01 for all values). In instances of discordance between fitness and obesity, obesity was the stronger determinant of CM risk. In conclusion, fitness and obesity are independently associated with CM risk. The effects of fitness and obesity are additive, but obesity is more strongly associated with CM risk when fitness and obesity are discordant. These findings underscore the need for weight loss in obese patients and suggest an unmeasured benefit of fitness.


Calcination-free production of calcium hydroxide at sub-boiling temperatures.
Calcium hydroxide (Ca(OH)2), a commodity chemical, finds use in diverse industries ranging from food, to environmental remediation and construction. However, the current thermal process of Ca(OH)2 production via limestone calcination is energy- and CO2-intensive. Herein, we demonstrate a novel aqueous-phase calcination-free process to precipitate Ca(OH)2 from saturated solutions at sub-boiling temperatures in three steps. First, calcium was extracted from an archetypal alkaline industrial waste, a steel slag, to produce an alkaline leachate. Second, the leachate was concentrated using reverse osmosis (RO) processing. This elevated the Ca-abundance in the leachate to a level approaching Ca(OH)2 saturation at ambient temperature. Thereafter, Ca(OH)2 was precipitated from the concentrated leachate by forcing a temperature excursion in excess of 65 °C while exploiting the retrograde solubility of Ca(OH)2. This nature of temperature swing can be forced using low-grade waste heat (≤100 °C) as is often available at power generation, and industrial facilities, or using solar thermal heat. Based on a detailed accounting of the mass and energy balances, this new process offers at least ≈65% lower CO2 emissions than incumbent methods of Ca(OH)2, and potentially, cement production.


[Glutamate decarboxylase and GABA transaminase activity in the mitochondrial fraction of the dog brain limbic system during postnatal development].
Overall glutamate decarboxylase (GDCase) activity in the initial mitochondrial fraction of the limbic structure is found to be regionally different it increases from the moment of birth up to 1 year, the midbrain reticular formation (RF), where the enzyme activity in the mitochondrial decreases in pups aged 3 month and reincreases in 1 year old dogs being the exception. Overall GABA-transaminase (GABA-T-ase) activity reaches the "adult" level and is the highest: in the hypothalamic and hippocampal mitochondria on the 1st postnatal day; in the limbic cortex (l1 and l2 fields), amygdala and midbrain RF--on the 12-16th postnatal days. During the period from 12-16 postnatal days up to the age of 1 year GABA-T-ase activity in the dog limbic system decreases reliably.


Antimicrobial activity of lavender, tea tree and lemon oils in cosmetic preservative systems.
The aim of the study was to verify the antimicrobial activity of commercial essential oils: lavender, tea tree and lemon as the components of a preservative system in oil in water body milks. The inhibition efficacy of essential oils alone (0.5%), in mixtures (1%) as well as combined with the synthetic preservative 1,3-dimethylol-5,5-dimethylhydantoin and a 3-iodo-2-propynyl butyl carbamate mixture (0.1% and 0.2%) was tested against Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Candida sp. ŁOCK 0008 and Aspergillus niger ATCC 16404 in compliance with the standards of the European Pharmacopoeia Commission. The in vitro activity of oils determined by an impedimetric method was also compared with their activity in cosmetic preparations. Criterion A for bacteria (reduction in the inoculum by 3 logarithmic units within 7 days with no increase up to the 28th day) and fungi (reduction in the inoculum by 2 logarithmic units within 14 days with no increase up to the 28th day) was fulfilled for cosmetic formulations containing the tested essential oils with 0.2% of the synthetic preservative. The preservative concentration could be decreased to 0.1% (with preserving the same efficacy) in combination with lavender and tea tree oils at a concentration of 0.5% each. In all combinations of essential oils with the synthetic preservative, a synergistic effect of the preservative system components was observed, which made it possible to reduce the usable level of the synthetic preservative up to 8.5 times. To develop an effective preservative system in cosmetics in which a synthetic chemical preservative is replaced by natural essential oils.


Glycogen metabolic genes are involved in trehalose-6-phosphate synthase-mediated regulation of pathogenicity by the rice blast fungus Magnaporthe oryzae.
The filamentous fungus Magnaporthe oryzae is the causal agent of rice blast disease. Here we show that glycogen metabolic genes play an important role in plant infection by M. oryzae. Targeted deletion of AGL1 and GPH1, which encode amyloglucosidase and glycogen phosphorylase, respectively, prevented mobilisation of glycogen stores during appressorium development and caused a significant reduction in the ability of M. oryzae to cause rice blast disease. By contrast, targeted mutation of GSN1, which encodes glycogen synthase, significantly reduced the synthesis of intracellular glycogen, but had no effect on fungal pathogenicity. We found that loss of AGL1 and GPH1 led to a reduction in expression of TPS1 and TPS3, which encode components of the trehalose-6-phosphate synthase complex, that acts as a genetic switch in M. oryzae. Tps1 responds to glucose-6-phosphate levels and the balance of NADP/NADPH to regulate virulence-associated gene expression, in association with Nmr transcriptional inhibitors. We show that deletion of the NMR3 transcriptional inhibitor gene partially restores virulence to a Δagl1Δgph1 mutant, suggesting that glycogen metabolic genes are necessary for operation of the NADPH-dependent genetic switch in M. oryzae.


Follow-up study of anxiety disorder and alcohol dependence in comorbid alcoholism treatment patients.
Anxiety disorders are present in a high percentage of alcoholism treatment patients. We tested the prediction that having a comorbid anxiety disorder increases the prospective risk for relapse to drinking after alcoholism treatment. We also explored the prospective associations of specific anxiety syndromes (and depression) with drinking and anxiety outcomes. We assessed the diagnostic status and daily drinking patterns of 82 individuals approximately one week after they entered alcoholism treatment (baseline) and again approximately 120 days later (follow-up) (n=53). Consistent with study predictions, those with a baseline anxiety disorder (approximately 55%) were significantly more likely than others to meet various definitions of drinking relapse over the course of the follow-up. Regression models showed that baseline social phobia was the single best predictor of a return to any drinking after treatment, whereas panic disorder was the single best predictor of a relapse to alcohol dependence after treatment. Having multiple anxiety disorders (versus any specific anxiety disorder) at the baseline was the strongest predictor of having at least one active ("persistent") anxiety disorder at the follow-up. Cross-sectional analysis at the follow-up showed that anxiety disorder persisted in the absence of a relapse to alcohol dependence far more often than relapse to alcohol dependence occurred in the absence of a persistent anxiety disorder. Screening for comorbid anxiety disorder in alcoholism treatment patients is warranted and, where found, should be considered a marker of high relapse risk relative to that of noncomorbid patients. The capacity of specific anxiety treatment to mitigate relapse risk among comorbid patients remains an open question.


The 20-year outcome of the charnley arthroplasty in younger and older patients.
The purpose of this study is to present the 20-year outcome of 206 Charnley low-friction arthroplasties done by the same surgeon on 181 patients who were separated into two age groups (younger and older). In Group A (76 patients, 92 hips) the mean age at surgery was 44 years (range, 24-55 years), and in Group B (105 patients, 114 hips) the mean age at surgery was 65 years (range, 56-82 years). All patients were evaluated clinically and radiographically. At final followup, 71 patients (87 hips) in Group A and 90 patients (99 hips) in Group B were available for study. The overall failure rate for the hips of Group A was 37.9%, and the overall failure rate for the hips of Group B was 20%. The main cause of failure in Group A was aseptic loosening of the components and breakage of the femoral stem, whereas in Group B the main cause of failure was deep infection. We concluded that by eliminating the above factors, and using new cementing techniques and improved implants, the 20-year results of this arthroplasty would be better. Our results show that the Charnley arthroplasty is a reliable procedure for hip replacement, even in younger patients.


Impact of N-Acyl-Homoserine Lactones, Quorum Sensing Molecules, on Gut Immunity.
Among numerous molecules found in the gut ecosystem, quorum sensing (QS) molecules represent an overlooked part that warrants highlighting. QS relies on the release of small molecules (auto-inducers) by bacteria that accumulate in the environment depending on bacterial cell density. These molecules not only are sensed by the microbial community but also interact with host cells and contribute to gut homeostasis. It therefore appears entirely appropriate to highlight the role of these molecules on the immune system in dysbiosis-associated inflammatory conditions where the bacterial populations are imbalanced. Here, we intent to focus on one of the most studied QS molecule family, namely, the type I auto-inducers represented by N-acyl-homoserine lactones (AHL). First described in pathogens such as Pseudomonas aeruginosa, these molecules have also been found in commensals and have been recently described within the complex microbial communities of the mammalian intestinal tract. In this mini-review, we will expound on this emergent field of research. We will first recall evidence on AHL structure, synthesis, receptors, and functions regarding interbacterial communication. Then, we will discuss their interactions with the host and particularly with agents of the innate and adaptive gut mucosa immunity. This will reveal how this new set of molecules, driven by microbial imbalance, can interact with inflammation pathways and could be a potential target in inflammatory bowel disease (IBD). The discovery of the general impact of these compounds on the detection of the bacterial quorum and on the dynamic and immune responses of eukaryotic cells opens up a new field of pathophysiology.


Interactions between serum vitamin D levels and vitamin D receptor gene FokI polymorphisms for renal function in patients with type 2 diabetes.
We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels. 1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3 ~ 5 but not stage 1 ~ 2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65). These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.


Quartz Crystal Microbalance Platform for SARS-CoV-2 Immuno-Diagnostics.
Rapid and accurate serological analysis of SARS-CoV-2 antibodies is important for assessing immune protection from vaccination or infection of individuals and for projecting virus spread within a population. The quartz crystal microbalance (QCM) is a label-free flow-based sensor platform that offers an opportunity to detect the binding of a fluid-phase ligand to an immobilized target molecule in real time. A QCM-based assay was developed for the detection of SARS-CoV-2 antibody binding and evaluated for assay reproducibility. The assay was cross-compared to the Roche electrochemiluminescence assay (ECLIA) Elecsys® Anti-SARS-CoV-2 serology test kit and YHLO's chemiluminescence immunoassay (CLIA). The day-to-day reproducibility of the assay had a correlation of r2 = 0.99, p < 0.001. The assay linearity was r2 = 0.96, p < 0.001, for dilution in both serum and buffer. In the cross-comparison analysis of 119 human serum samples, 59 were positive in the Roche, 52 in the YHLO, and 48 in the QCM immunoassay. Despite differences in the detection method and antigen used for antibody capture, there was good coherence between the assays, 80-100% for positive and 96-100% for negative test results. In summation, the QCM-based SARS-CoV-2 IgG immunoassay showed high reproducibility and linearity, along with good coherence with the ELISA-based assays. Still, factors including antibody titer and antigen-binding affinity may differentially affect the various assays' responses.


Vaccination in the elderly: what can be recommended?
The age-associated increased susceptibility to infectious disease would suggest that vaccination should be a route to promote healthy aging and keep our seniors autonomous and independent. While vaccination represents a cost-effective and efficient strategy at community level, the ability of the immune system to mount a protective immune response is still unpredictable at the level of the individual. Thus, at a similar age, some individuals, including the elderly, might still be 'good' responders while some other, even younger, would definitely fail to mount a protective response. In this review, the current burden of vaccine-preventable diseases in the aging and aged population will be detailed with the aim to identify the ideal vaccine candidates over the age of 50 years. This article will conclude with potential strategies to reduce, as best as possible, this burden and the imperative need to overcome barriers in extending current vaccine coverage towards to a lifelong vaccine schedule.


Vibrational Spectroscopic Based Approach for Diagnosing Babesia bovis Infection.
Babesia bovis parasites present a serious and significant health concern for the beef and dairy industries in many parts of the world. Difficulties associated with the current diagnostic techniques include the following: they are prone to human error (microscopy) or expensive and time-consuming (polymerase chain reaction) to perform. Little is known about the biochemical changes in blood that are associated with Babesia infections. The discovery of new biomarkers will lead to improved diagnostic outcomes for the cattle industry. Vibrational spectroscopic technologies can record a chemical snapshot of the entire organism and the surrounding cell thereby providing a phenotype of the organism and the host infected cell. Here, we demonstrate the applicability of vibrational spectroscopic imaging techniques including Atomic Force Microscopy Infrared (AFM-IR) and confocal Raman microscopy to discover new biomarkers for B. bovis infections. Furthermore, we applied Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) to detect B. bovis in red blood cells (RBCs). Based on changes in the IR spectral bands, with ATR-FTIR in combination with Partial Least Squares-Discriminant Analysis we were able to discriminate infected samples from controls with a sensitivity and specificity of 92.0% and 91.7%, respectively, in less than 2 min, excluding sample extraction and preparation. The proposed method utilized a lysis approach to remove hemoglobin from the suspension of infected and uninfected cells, which significantly increased the sensitivity and specificity compared to measurements performed on intact infected red blood cells (intact infected RBC, 77.3% and 79.2%). This work represents a holistic spectroscopic study from the level of the single infected RBC using AFM-IR and confocal Raman to the detection of the parasite in a cell population using ATR-FTIR for a babesiosis diagnostic.


[The evolution of the forms of hermaphroditism in Cyclophyllidea (Cestoda). 2. Morphofunctional causes of the formation of tapeworms having a protogynous type of the genital apparatus development].
Morpho-biological causes of the formation of protogynous forms of Anoplocephalidae (Cyclophyllidea) parasitizing rodents have been studied. The reduction in the number of segments in the strobila of anoplocephalideans (Anoplocephaloides, Paranoplocephaloides) in comparison with related polymeric species of the taxon (Paranoplocephala) suggests that protogyny is resulted from the secondary oligomerization of strobila in the phylogenesis of these cestodes. It is evident that the ecological cause of the selection for a small number of segments in the strobila is a tough competition among large polymeric cestodes that results in the formation of small anoplocephalideans located in the back part of the small intestine (Paranoplocephaloides) and in the blind gut (Anoplocephaloides) of rodents. There is slowing down of strobilation rates, acceleration of genital apparatus development and somatic proglottid morphogenesis during the change into protogyny. Due to an earlier, regarding testicle morphogenesis, formation of the ovary and uterus, uterus segments are developing most of the time in the strobila. Thus, proterogyny is one of the universal mechanisms to extend the terms of hexacanth embryogenesis in the second oligomeric strobila of tapeworms.


Healthy diet and lifestyle clustering and glucose intolerance.
Glucose intolerance represents a spectrum of abnormalities, including impaired fasting glucose, impaired glucose tolerance and type 2 diabetes. It is a major public health challenge worldwide, with rapidly increasing prevalence rates in both developed and developing countries. This global epidemic of diabetes is largely driven by the globalisation of Western culture and lifestyles. Specifically, there is now evidence from large-scale observational studies, and from intervention studies, of powerful synergistic interactions between diet, obesity, exercise, smoking and alcohol in the development of glucose intolerance. It is estimated that >90% of cases of type 2 diabetes in the population could be prevented with the adoption of a prudent diet (high in cereal fibre and polyunsaturated fatty acids and low in trans-fatty acids and glycaemic load), avoidance of overweight and obesity (BMI<25 kg/m2), engagement in moderate to vigorous physical activity for at least 0.5 h/d, non-smoking and moderate alcohol consumption. These findings are biologically plausible and have major public health implications. They form the basis for a clear, simple and coherent message for health promotion and public policy. However, to make progress on these issues health will need to be placed at the centre of public policy and relevant vested interests tackled, notably in the food, entertainment, tobacco and automobile industries.


A review of the clinical and diagnostic utility of laboratory tests for the detection of congenital thrombophilia.
Laboratory tests to detect congenital thrombophilia are frequently requested by clinicians. This review attempts to define (1) whether and to what extent laboratory testing may help clinicians make decisions on patient management, (2) the types of conditions to be investigated, and (3) the types of testing to be performed for each condition.


Regulatory T cells ameliorate acetaminophen-induced immune-mediated liver injury.
The contribution of innate immune cells to acetaminophen (APAP)-induced liver injury has been extensively investigated. However, the roles of T cell populations among adaptive immune cells in APAP-induced liver injury remain to be elucidated. Herein, we found that distinct CD4(+) T cell subsets but not CD8(+) T cells modulated APAP-induced liver injury in mice. After APAP challenge, more CD62L(low)CD44(hi)CD4(+) T cells appeared in the liver, accompanied by increased IFN-γ. The removal of CD4(+) T cells by either antibody depletion or genetic deficiency markedly compromised pro-inflammatory cytokine levels and ameliorated liver injury. Meanwhile, we also found that the frequency and absolute number of Treg cells also increased. Treg cell depletion increased hepatic CD62L(low)CD44(hi)CD4(+) T cells, augmented pro-inflammatory cytokines, and exacerbated liver injury, while adoptive transfer of Treg cells ameliorated APAP-induced liver injury. Furthermore, the recruitment of Treg cells into the liver through specific expression of CXCL10 in the liver could ameliorate APAP-induced liver injury. Our investigation suggests that Th1 and Treg subsets are involved in regulating APAP-induced liver injury. Thus, modulating the Th1/Treg balance may be an effective strategy to prevent and/or treat APAP-induced liver injury.


Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.
Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.


Taste stimuli: time course of peripheral nerve response and theoretical models.
The responses of a taste nerve in rats to sodium chloride were integrated over successive 10-millisecond intervals and averaged. The time course of the mean responses consisted of a 30-millisecond latency, a rapid rise to a maximum, and a slower decline to a sustained level. The chemoreceptor theories of Beidler and Paton failed to predict the relation between phasic response and time or concentration.


Development and implementation of a novel measure for quantifying training loads in rowing: the T2minute method.
The systematic management of training requires accurate training load measurement. However, quantifying the training of elite Australian rowers is challenging because of (a) the multicenter, multistate structure of the national program; (b) the variety of training undertaken; and (c) the limitations of existing methods for quantifying the loads accumulated from varied training formats. Therefore, the purpose of this project was to develop a new measure for quantifying training loads in rowing (the T2minute method). Sport scientists and senior coaches at the National Rowing Center of Excellence collaborated to develop the measure, which incorporates training duration, intensity, and mode to quantify a single index of training load. To account for training at different intensities, the method uses standardized intensity zones (T zones) established at the Australian Institute of Sport. Each zone was assigned a weighting factor according to the curvilinear relationship between power output and blood lactate response. Each training mode was assigned a weighting factor based on whether coaches perceived it to be "harder" or "easier" than on-water rowing. A common measurement unit, the T2minute, was defined to normalize sessions in different modes to a single index of load; one T2minute is equivalent to 1 minute of on-water single scull rowing at T2 intensity (approximately 60-72% VO2max). The T2minute method was successfully implemented to support national training strategies in Australian high performance rowing. By incorporating duration, intensity, and mode, the T2minute method extends the concepts that underpin current load measures, providing 1 consistent system to quantify loads from varied training formats.


The Role of Autosensitivity Control (ASC) in Cochlear Implant Recipients.
The purpose of the study was to examine the subjective and objective potential advantage for speech understanding in noise achieved by cochlear implant (CI) recipients when using the autosensitivity control (ASC) input signal processing in combination with the adaptive dynamic range optimization (ADRO). Eighteen subjects (8 females, 10 males, mean age 17.7 ± 6.7) were enrolled in a prospective open blinded comparative study between the ASC + ADRO condition vs. the ADRO alone; 16 were sequential binaural and 2 were monoaural CI recipients. All patients had been wearing their CI for at least 3 years, had no additional disabilities, had an age-appropriate receptive and expressive language. Word recognition performances in noise (at signal-to-noise ratio +5 dB HL) were significantly better in the ADRO-alone condition than in the ADRO + ASC condition. (p = 0.03) These objective outcomes were in agreement with the subjective reports. No significant difference was found in quiet. Our results, apparently in contrast with other reports in the literature, suggest that the decision of adding the slow-acting automatic reduction in microphone sensitivity provided by ASC should be limited to selected CI recipients.


Parental imprinting and Angelman syndrome.
Angelman syndrome is an inherited disorder that includes severe mental retardation and epilepsy. Patients have no speech, puppet-like gait with jerky movements, hyperactivity, disturbed sleep, bouts of inappropriate laughter, a pronounced jaw, and widely spaced teeth. The syndrome results from deletion or mutation within maternal chromosome 15q11-q13. Considerable evidence suggests that the gene or genes responsible for Angelman syndrome are expressed only from the maternal chromosome 15, a situation known as parental imprinting. This epigenetic marking of certain regions of the parental genomes is characterized by parent-of-origin-specific allelic DNA methylation, allele-specific DNA replication timing, and physical pairing of the two chromosome 15 homologues. Imprinting is important for normal development, and its disregulation causes several human disorders. The epilepsy of Angelman syndrome has been studied and indicates a rather typical electroencephalographic abnormality with slowing and notched wave and spikes. Various types of seizures occur, usually including myoclonus and atypical absence. Variable severity among patients suggests potential molecular diversity in the genetic mechanism, possibly the involvement of more than one gene. Angelman syndrome can arise from the following molecular genetic defects: a deletion in 15q11-q13 that covers the Angelman gene or genes, mutations that alter imprinting, and paternal uni-parental disomy for the region. Another 20% or so of patients with clinical symptoms of Angelman syndrome have none of these three defects but are believed to have mutations in one or more genes in the region, and this may be familial. The UBE3A gene, which codes for the enzyme ubiquitin protein ligase involved in protein degradation and processing, has been found to be mutated in many but not all of patients with Angelman syndrome and can be considered a major Angelman candidate gene. Other potential candidate genes in the region include a cluster of three GABAA receptor subunits, which are involved in inhibitory synaptic transmission in the brain. The GABRB3 gene, which codes for the beta 3 subunit, is deleted in most persons with Angelman syndrome. The absence of this gene in mice causes craniofacial abnormalities and neurologic impairment with seizures. The exact role of UBE3A and GABRB3 in the syndrome and their imprinting status are under investigation.


Multisubject independent component analysis of fMRI: a decade of intrinsic networks, default mode, and neurodiagnostic discovery.
Since the discovery of functional connectivity in fMRI data (i.e., temporal correlations between spatially distinct regions of the brain) there has been a considerable amount of work in this field. One important focus has been on the analysis of brain connectivity using the concept of networks instead of regions. Approximately ten years ago, two important research areas grew out of this concept. First, a network proposed to be "a default mode of brain function" since dubbed the default mode network was proposed by Raichle. Secondly, multisubject or group independent component analysis (ICA) provided a data-driven approach to study properties of brain networks, including the default mode network. In this paper, we provide a focused review of how ICA has contributed to the study of intrinsic networks. We discuss some methodological considerations for group ICA and highlight multiple analytic approaches for studying brain networks. We also show examples of some of the differences observed in the default mode and resting networks in the diseased brain. In summary, we are in exciting times and still just beginning to reap the benefits of the richness of functional brain networks as well as available analytic approaches.


[Therapeutic potential of ginseng root preparations in treating diabetes mellitus].
Biologically active substances of some medicinal plants (ginseng, rhodiola, eleutherococcus, etc.) classified as adaptogens possess a broad spectrum of pharmacological properties. In additional to influencing the central nervous system (antistressor, psychotonic, and nootropic effects), these substances also affect various internal organs. The present review of published data shows that, in particular, ginseng root preparations possess pronounced antidiabetic properties and, hence, can be more widely used in clinical endocrinology.


Exploring the Design and Role of Mobile Apps for Healthcare Providers to Find Teratogenic Information.
Healthcare providers (HCPs) caring for pregnant patients often need information on drug risks to the embryo or fetus, but such complex information takes time to find and is difficult to convey on an app. In this work, we first surveyed 167 HCPs to understand their current teratogen information-seeking practices to help inform our general design goals. Using the insights gained, we then designed a prototype of a mobile app and tested it with 22 HCPs. We learned that HCP 's information needs in this context can be grouped into 3 types: to understand, to decide, and to explain. Different sets of information and features may be needed to support these different needs. Further, while some HCPs had concerns about appearing unprofessional and unknowledgeable when using the app in front of patients, many did not. They noted that incorporating mobile information apps into practice improves information access, can help signal care and technology-savviness, in addition to providing an opportunity to engage and educate patients. Implications for design and additional features for reference apps for HCPs are discussed.


MEGAnnotator2: a pipeline for the assembly and annotation of microbial genomes.
The reconstruction of microbial genome sequences by bioinformatic pipelines and the consequent functional annotation of their genes' repertoire are fundamental activities aiming at unveiling their biological mechanisms, such as metabolism, virulence factors, and antimicrobial resistances. Here, we describe the development of the MEGAnnotator2 pipeline able to manage all next-generation sequencing methodologies producing short- and long-read DNA sequences. Starting from raw sequencing data, the updated pipeline can manage multiple analyses leading to the assembly of high-quality genome sequences and the functional classification of their genetic repertoire, providing the user with a useful report constituting features and statistics related to the microbial genome. The updated pipeline is fully automated from the installation to the delivery of the output, thus requiring minimal bioinformatics knowledge to be executed.


Improved C3-4 transfer for treatment of root avulsion of the brachial plexus upper trunk: Animal experiments and clinical application.
Experimental rats with root avulsion of the brachial plexus upper trunk were treated with the improved C3-4 transfer for neurotization of C5-6. Results showed that Terzis grooming test scores were significantly increased at 6 months after treatment, the latency of C5-6 motor evoked potential was gradually shortened, and the amplitude was gradually increased. The rate of C3 instead of C5 and the C4 + phrenic nerve instead of C6 myelinated nerve fibers crossing through the anastomotic stoma was approximately 80%. Myelinated nerve fibers were arranged loosely but the thickness of the myelin sheath was similar to that of the healthy side. In clinical applications, 39 patients with root avulsion of the brachial plexus upper trunk were followed for 6 months to 4.5 years after treatment using the improved C3 instead of C5 nerve root transfer and C4 nerve root and phrenic nerve instead of C6 nerve root transfer. Results showed that the strength of the brachial biceps and deltoid muscles recovered to level III-IV, scapular muscle to level III-IV, latissimus dorsi and pectoralis major muscles to above level III, and the brachial triceps muscle to level 0-III. Results showed that the improved C3-4 transfer for root avulsion of the brachial plexus upper trunk in animal models is similar to clinical findings and that C3-4 and the phrenic nerve transfer for neurotization of C5-6 can innervate the avulsed brachial plexus upper trunk and promote the recovery of nerve function in the upper extremity.


YouTube Doctors Confronting COVID-19: Scientific-Medical Dissemination on YouTube during the Outbreak of the Coronavirus Crisis.
The coronavirus crisis has highlighted the consumption of social media and online video platforms in search of an alternative discourse to that provided by traditional media. The objective of this article is to find an approach to education and scientific dissemination on COVID-19 present in the Spanish context of YouTube, focusing on the content analysis of audiovisual texts generated by creators from the medical and biomedical fields. A methodological orientation was used for this based on the Grounded Theory, which was applied to five case studies whose informative material on SARS-CoV-2 exceeded ten million views as of March 2021. The results reveal the existence of a group of medical professionals in the Spanish YouTube sphere who, since the COVID-19 outbreak, have been involved in the construction of an alternative discourse around the health crisis and its evolution that pursues a high standard of audiovisual quality, scientific rigor, and educational ability.


Protein-enriched pea flour extract protects stored milled rice against the rice weevil, Sitophilus oryzae.
Studies were conducted to evaluate the effect of a protein-enriched pea (Pisum sativum var. Bonneville) flour extract against the rice weevil, Sitophilus oryzae in its repellency, toxicity, effect on fecundity, stability and sensory properties. Milled rice admixed with pea flour extract at 1% concentration significantly repelled S. oryzae. Mortality of S. oryzae was found to increase and fecundity was markedly suppressed, in rice treated with 1% pea flour extract. The toxicity and reproductive effects of the pea protein-enriched rice were found to be stable for a period of 5 months. The sensory characteristics of stored rice when eaten were not affected by the treatment with pea flour extract. This study indicates that the protein-enriched flour extract obtained from the Bonneville pea may be feasible to protect stored milled rice from insect attack.


Isolation and characterization of the lignans, isolariciresinol and pinoresinol, in flaxseed meal.
The isolation and characterization of the lignans, isolariciresinol, pinoresinol, secoisolariciresinol, and matairesinol, potent phytoestrogens, from flaxseed meal are described. This is the first report of isolariciresinol and pinoresinol being detected in a food. The extraction method selected combined the removal of the lignan glycosides from the plant matrix with an alcoholic solvent system, followed by acid hydrolysis to release the aglycons. A reversed-phase high-performance liquid chromatography with diode array detection system was used for initial separation and detection of the lignans at 280 nm in the acid-hydrolyzed methanolic extract. Lignan trimethylsilyl ether derivatives were characterized by gas chromatography/mass spectrometry. Secoisolariciresinol is the major lignan in flaxseed; isolariciresinol, pinoresinol, and matairesinol were identified as minor lignan components.


Cardioprotection in the clinical setting-lessons from J-WIND studies.
Both prevention and attenuation of ischemic heart disease are important issues, and there are three different strategies to save patients from the deleterious sequelae of ischemic injury. The first strategy is to remove the causes of ischemic heart disease; the second is to attenuate on-going ischemic and reperfusion injury; the third is to prevent the progression of cardiac remodeling and chronic heart failure following ischemic injury. For prevention of acute myocardial infarction, it is widely accepted to treat high risk patients with aspirin and/or statins. On the other hand, several medications such as angiotensin converting enzyme inhibitors, aldosterone receptor antagonists and beta blockers have been used for the prevention of post-infarction heart failure in patients who have suffered from an acute myocardial infarction. However, at present we do not have an adjunctive drug therapy to reduce infarct size in the acute phase in patients with myocardial infarction. Recently, the J-WIND trials suggested that an infusion of human atrial natriuretic peptide in the acute phase and oral administration of nicorandil in the chronic phase of infarction result in a better outcome in patients with a myocardial infarction. In this article we propose potential mechanisms for cardioprotection in patients with an acute myocardial infarction.


Stakeholder development of an implementation strategy for fall prevention in Norwegian home care - a qualitative co-creation approach.
The uptake of fall prevention evidence has been slow and limited in home care services. Involving stakeholders in the implementation process is suggested as a method to successfully tailor implementation strategies. The aim of this study was to develop an implementation strategy for fall prevention, targeting healthcare providers working in home care services. This study used an explorative qualitative approach in a five-step co-creation process to involve researchers, service users, and healthcare providers. The first two steps consisted of workshops. This was followed by focus group interviews and individual interviews with key informants as steps three and four. Data from the first four steps were analyzed using reflexive thematic analysis. The fifth and final step was a workshop finalizing a strategy for implementing fall prevention evidence in home health services. Overall, our findings, resulted in an implementation strategy for fall prevention with four components: (1) Empower leaders to facilitate implementation, operationalized through what managers pay attention to regularly, resource priorities, and time spent on fall prevention, (2) Establish implementation teams, consisting of multidisciplinary healthcare providers from different levels of the organization, with formalized responsibility for implementation, (3) Tailor dual competence improvement, reflecting the need for knowledge and skills for fall prevention and implementation among healthcare providers and users, and (4) Provide implementation support, representing guidance through the implementation process. This study advances our understanding of implementation in home care services. Implementation of fall prevention requires an implementation strategy involving a blend of essential components targeting leaders, competent healthcare providers and users, and establishing structures enhancing the implementation process.