A comparison of four nursing documentation systems.
Nurses must be able to keep charts effectively and efficiently while providing high-quality care. Often, nurse educators are responsible for finding a workable system for a particular institution. This article reviews four nursing documentation systems that can be used in a variety of health care settings: Problem Centered, PIE (Problem Intervention Evaluation), Focus, and Charting by Exception.


Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis.
Pulmonary fibrosis (PF) is one of the pathologic changes in COVID-19 patients in convalescence, and it is also a potential long-term sequela in severe COVID-19 patients. Qimai Feiluoping decoction (QM) is a traditional Chinese medicine formula recommended in the Chinese national medical program for COVID-19 convalescent patients, and PF is one of its indications. Through clinical observation, QM was found to improve the clinical symptoms and pulmonary function and reduce the degree of PF of COVID-19 convalescent patients. To further explore the pharmacological mechanisms and possible active components of QM in anti-PF effect, UHPLC/Q-TOF-MS was used to analyze the composition of the QM extract and the active components that can be absorbed into the blood, leading to the identification of 56 chemical compounds and 10 active components. Then, network pharmacology was used to predict the potential mechanisms and targets of QM; it predicted that QM exerts its anti-PF effects via the regulation of the epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) degradation, and TGF-β signaling pathway. Finally, TGF-β1-induced A549 cells were used to verify and explore the pharmacological effects of QM and found that QM could inhibit the proliferation of TGF-β1-induced A549 cells, attenuate EMT, and promote ECM degradation by inhibiting the TGF-β/Smad3 pathway.


Older adults with heel ulcers in the acute care setting: frequency of noninvasive vascular assessment, surgical intervention, and 1-year mortality.
To examine how often hospitalized older adults with a diagnosis of heel ulcers are evaluated with noninvasive vascular tests and to determine the impact of invasive vascular or surgical procedures on 1-year mortality. Retrospective review using an electronic database and chart review of all patients discharged with a diagnosis of heel ulcer between 2006 and 2009. Urban teaching hospital. A total of 506 participants aged 65 years and older. Data collected included resident characteristics (demographics, medical history, and severity of illness using the Charlson comorbidity index), staging of heel ulcers, rates of noninvasive vascular assessments, vascular and surgical procedures, length of stay, and 1-year mortality. Thirty-one percent (155/506) of patients with a heel ulcer underwent noninvasive vascular testing and of these 83% (129/155) were found to have underlying ischemia. Twenty-six percent (130/506) of patients underwent at least 1 vascular or surgical procedure. The 1-year mortality rate for patients with stage 1 or 2 disease was 55%; this rose to 70% for patients with stage 3 or 4 ulcers (P = .01), and could not be explained by differences in the Charlson comorbidity index. Patients who underwent a vascular or surgical procedure had a significantly lower mortality compared with those who did not (59% vs 68% P = .04). Older adults with a heel ulcer in the acute care setting are frequently not assessed for underlying ischemia of the lower extremities. The diagnosis carries high 1-year mortality rates. Evidence-based protocols need to be developed to determine which older adults should have a vascular assessment and then undergo an invasive procedure.


Rethinking Opioids, Gabapentinoids, and Pain.
Through the use of opiate analgesia, it is possible to alter perceptions of pain, but equally, these same drugs have the potential to cause other profound consequences. Long before the COVID-19 pandemic began to impact societies worldwide, many developed nations (and particularly the United States) were caught up in a struggle to contain the consequences of opioid use, which has directly contributed to numerous deaths and ongoing disability for many others.


Predictive value of PIVKA-II and AFP for the non-objective response of HBV-associated hepatocellular carcinoma after transarterial chemoembolization: a prospective study.
To determine the predictive value of serum abnormal prothrombin (PIVKA-II) and alpha-fetoprotein (AFP) for the non-objective response of HBV-associated hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). This prospective study included HBV-associated HCC patients who underwent TACE at the Fourth People's Hospital of Qinghai Province between December 2021 and July 2022. According to contrast-enhanced ultrasound and upper abdomen contrast-enhanced MRI, the patients were divided into the objective response group and the non-objective response group 3 months after TACE. There were 54 patients, of whom 31 experienced non-objective responses. The PIVKA-II levels in the objective response group were significantly lower than in the non-objective response group at 1 month [352.00 (142.16-722.54) vs. 528.58(241.32-1681.23) mAU/ml, P = 0.005] and 3 months [28.96 (20.01-42.49) vs. 2082.55 (52.63-10 057.30) mAU/ml, P = 0.016] after TACE. The Spearman rank correlation analysis showed no significant correlation between PIVKA-II and AFP (r = 0.315, P > 0.05). The areas under the curve (AUCs) of AFP and PIVKA-II before TACE were 0.632 and 0.529. One month after TACE, the AUC of PIVKA-II combined with AFP (AUC = 0.787) was higher than for PIVKA-II (AUC = 0.658) and AFP (AUC = 0.749). PIVKA-II does not outperform AFP in predicting non-objective response after TACE in HCC patients. The combination of PIVKA-II and AFP might improve the diagnosis of HCC non-objective response after TACE.


Functional interaction between human papillomavirus type 16 E6 and E7 oncoproteins and cigarette smoke components in lung epithelial cells.
The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction between HPV infection and smoke carcinogens, however, remains unclear. In this study we address a potential cooperation between tobacco smoke and HPV16 E6 and E7 oncoproteins for alterations in proliferative and tumorigenic properties of lung epithelial cells. A549 (alveolar, tumoral) and BEAS-2B (bronchial, non-tumoral) cell lines were stably transfected with recombinant pLXSN vectors expressing HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC) at different concentrations. HPV16 E6 and E7 expression was associated with loss of p53 stability, telomerase (hTERT) and p16(INK4A) overexpression in BEAS-2B cells as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). In A549 cells we observed downregulation of p53 but not a significant increase of hTERT transcripts. In addition, the HPV16 E6/E7 transfected cell lines showed an increased proliferation rate and anchorage-independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover, both HPV16 E6/E7 and mock transfected cells showed an increased proliferation rate and anchorage-independent growth in the presence of 0.1 and 10 µg/mL CSC. However, this increase was significantly greater in HPV16 E6/E7 transfected cells (p<0.001). Data were confirmed by FCSE proliferation assay. The results obtained in this study are suggestive of a functional interaction between tobacco smoke and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of lung epithelial cells. More studies are warranted in order to dissect the molecular mechanisms involved in this cooperation.


Pharmacokinetics and Safety of Letermovir Coadministered With Cyclosporine A or Tacrolimus in Healthy Subjects.
Letermovir is being developed for human cytomegalovirus infection treatment and prophylaxis. In patients receiving transplants, antivirals are coadministered with cyclosporine A (CsA) or tacrolimus (TAC) immunosuppressants. Therefore, we investigated the potential for letermovir-immunosuppressant interactions. In 2 phase 1 clinical trials either CsA 50 mg or TAC 5 mg was administered to healthy males. Following washout, letermovir 80 mg was dosed twice daily for 7 and 11 days in the CsA and TAC trials, respectively, with a second dose of immunosuppressant coadministered with letermovir at steady state. In addition, letermovir 40 mg twice daily was administered for 14 days, and either CsA 50 or 200 mg administered on days 7 and 14. Pharmacokinetics and tolerability were assessed. Letermovir increased CsA and TAC Cmax by 37% and 70%, respectively, and exposure by 70% and 78%, respectively, compared with immunosuppressant alone; t½ was also increased from 10.7 to 17.9 hours for CsA. CsA (50/200 mg) increased letermovir Cmax,ss (109%/167%) and AUCss,τ (126%/237%) and decreased t½ (4.33 to 3.68/3.04 hours) versus letermovir alone. TAC did not significantly affect letermovir pharmacokinetics. All treatments were well tolerated. Concomitant letermovir increased TAC and CsA exposure. CsA altered letermovir pharmacokinetics, whereas TAC did not.


Activity Settings and Daily Routines in Preschool Classrooms: Diverse Experiences in Early Learning Settings for Low-Income Children.
This paper examines activity settings and daily classroom routines experienced by 3- and 4-year-old low-income children in public center-based preschool programs, private center-based programs, and family child care homes. Two daily routine profiles were identified using a time-sampling coding procedure: a High Free-Choice pattern in which children spent a majority of their day engaged in child-directed free-choice activity settings combined with relatively low amounts of teacher-directed activity, and a Structured-Balanced pattern in which children spent relatively equal proportions of their day engaged in child-directed free-choice activity settings and teacher-directed small- and whole-group activities. Daily routine profiles were associated with program type and curriculum use but not with measures of process quality. Children in Structured-Balanced classrooms had more opportunities to engage in language and literacy and math activities, whereas children in High Free-Choice classrooms had more opportunities for gross motor and fantasy play. Being in a Structured-Balanced classroom was associated with children's language scores but profiles were not associated with measures of children's math reasoning or socio-emotional behavior. Consideration of teachers' structuring of daily routines represents a valuable way to understand nuances in the provision of learning experiences for young children in the context of current views about developmentally appropriate practice and school readiness.


Piriformis syndrome: pain response outcomes following CT-guided injection and incremental value of botulinum toxin injection.
Piriformis syndrome is a common pain condition affecting the buttock and posterior hip with or without radiation to the leg, and management of the condition involves many treatments. In this study, we hypothesize that a CT-guided injection with botulinum toxin is more effective in providing pain relief than a CT-guided injection without Botox. Overall, 97 consecutive patients with piriformis syndrome presented for a CT-guided injection of the piriformis muscle and perineural injection of the sciatic nerve. After the injection, the patients received a visual analog scale pain log to record their pain level until the follow-up appointment. P values of less than 0.2 were considered as confounder and adjusted by inverse probability of treatment weighting (IPTW) via propensity score. The effect of botulinum toxin on 48-hour response and duration of response was tested using weighted chi-square test and weighted Kaplan-Meier analysis. There was a total of 97 patients in the study, and 111 injections, as some patients had bilateral injections. Patients in the Botox group had more 48-hour response than patients in the non-botulinum toxin group (P < 0.001 with IPTW, P = 0.005 without IPTW). Median pain-free survival was 30 days for Botox group and 1 day for non-Botox group (P = 0.059 with IPTW, P = 0.10 without IPTW). CT-guided injections with botulinum toxin for patients with piriformis syndrome are more likely to lead to a positive response and a longer duration of response than patients who receive a CT-guided injection without botulinum toxin. We hope that this study facilitates future prospective randomized blind trials for patients with suspected piriformis syndrome.


Selectivity of odorant receptors in insects.
Insect olfactory receptors (ORs) detect chemicals, shape neuronal physiology, and regulate behavior. Although ORs have been categorized as "generalists" and "specialists" based on their ligand spectrum, both electrophysiological studies and recent pharmacological investigations show that ORs specifically recognize non-pheromonal compounds, and that our understanding of odorant-selectivity mirrors our knowledge of insect chemical ecology. As we are progressively becoming aware that ORs are activated through a variety of mechanisms, the molecular basis of odorant-selectivity and the corollary notion of broad-tuning need to be re-examined from a pharmacological and evolutionary perspective.


Physician Preferences for Physician-Targeted HIV Testing Campaigns.
The U.S. Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force issued HIV testing recommendations, encouraging physicians to routinely test all adult patients for HIV. Studies have found that not all physicians are abiding by these guidelines, but that physician recommendations for HIV testing could encourage patients to get tested. Our study sought to determine physician preferences for a physician-targeted campaign to encourage them to offer HIV tests to their patients. The study took place across 19 publicly-funded community health centers. A web-based survey was sent to primary care physicians, assessing their preferences for physician-targeted HIV testing campaign elements. Response frequencies were calculated for each element. 175 physicians participated. Campaign elements were divided into "HIV Testing Information," "Communication Tools," and "Promotion Strategies." Physicians selected receiving a copy of the latest HIV testing recommendations, having patients ask for the HIV test, and receiving an EMR alert for HIV testing as their top elements for each category, respectively. An effective physician HIV testing campaign should include information about HIV testing recommendations, proof of patient receptiveness to HIV testing, and strategies to prompt HIV testing conversations. A multi-faceted approach combining patient and physician prompts to discuss HIV testing might be the most effective method to improve HIV testing rates.


Effects of salinity on cytosolic Na+ and K+ in root hairs of Arabidopsis thaliana: in vivo measurements using the fluorescent dyes SBFI and PBFI.
Toxicity from sodium accumulation is an important aspect of salinity stress that has been well studied at the organ and tissue level. However, the effects of salinity on sodium accumulation in the cytosol, where much of the sodium toxicity is thought to occur, are poorly understood due to the difficulty of direct non-invasive measurements of ion activities in living cells. The Na+-sensing fluorescent probe sodium-binding benzofuran isophthalate (SBFI) and the K+-sensing fluorescent probe potassium-binding benzofuran isophthalate (PBFI) were used to quantify Na+ and K+ activity in living root hairs under salinity stress. The effects of exposure of Arabidopsis thaliana roots to 0, 30, 60 or 90 mM NaCl were observed during the 20 min immediately following salinization and also after 2 d of salinization, in plants supplied with 0.5, 2.0 or 5.0 mM Ca. SBFI and PBFI fluorescence was confined primarily to the cytoplasm, with very little signal from the vacuole. Sodium affected the quantification of K+ by PBFI, thus limiting the usefulness of this dye. Root hairs exposed to NaCl accumulated from 30-60 mM Na+ within the first 5 min of salinization in 0.5 and 2.0 mM Ca2+, and up to 15 mM Na+ in the 5.0 mM Ca2+ treatment. Two days of salinization did not increase cytosolic Na+ concentrations beyond the values observed after 20 min of salinization. Cytosolic activities roughly corresponded with elemental analysis of combined dry matter fractions from whole plants. We conclude that SBFI and, to a lesser extent, PBFI are useful tools for quantifying the dynamics of ion activities in the cytosols of living plant cells.


Patterns of complementary and alternative medicine use in children with common neurological conditions.
Recent literature suggests that one in nine children in the United States uses some type of complementary and alternative medicine (CAM). Children with challenging neurological conditions such as headache, migraine, and seizures may seek CAM in their attempts at self-care. Our objective was to describe CAM use in children with these conditions. We compared use of CAM among children aged 3 to 17 years with and without common neurological conditions (headaches, migraines, seizures) where CAM might plausibly play a role in their self-management using the 2007 National Health Interview Survey (NHIS) data. Children with common neurological conditions reported significantly more CAM use compared to the children without these conditions (24.0% vs 12.6%, P<.0001). Compared to other pediatric CAM users, children with neurological conditions report similarly high use of biological therapies and significantly higher use of mind-body techniques (38.6% vs 20.5%, P<.007). Of the mind-body techniques, deep breathing (32.5%), meditation (15.1%), and progressive relaxation (10.1%) were used most frequently. About one in four children with common neurological conditions use CAM. The nature of CAM use in this population, as well as its risks and benefits in neurological disease, deserve further investigation.


Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma.
Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, theseanalogs could be considered for the LHRH receptor-based treatment of uveal melanoma.


Basic Knowledge about Metal Stent Development.
Biliary self-expandable metal stents (SEMS), a group of non-vascular stents, have been used in the palliative management of biliary obstruction around the world. However, there are still unmet needs in the clinical application of biliary SEMS. Comprehensive understanding of the SEMS is required to resolve the drawbacks and difficulties of metal stent development. The basic structure of SEMS, including the materials and knitting methods of metal wires, covering materials, and radiopaque markers, are discussed in this review. What we know about the physical and mechanical properties of the SEMS is very important. With an understanding of the basic knowledge of metal stents, hurdles such as stent occlusion, migration, and kinking can be overcome to develop more ideal SEMS.


Characteristics of Orthopaedic Malpractice Claims of Pediatric and Adult Patients in Private Practice.
Medical liability exposure varies based on scope of practice, patient demographics, and location of practice. There is a generally held belief that treatment of pediatric patients increases one's medicolegal risk. We examined a large national database of orthopaedic malpractice claims to determine if pediatric malpractice claims were associated with a less favorable medicolegal outcome compared with adults. Physician Insurers Association of America is an association of medical liability insurance carriers providing liability coverage for 60% of private practice physicians in the United States. The Physician Insurers Association of America data registry of closed medical liability claims was examined, including all orthopaedic claims between 1985 and 2012 in this review. Claims were categorized based on the age of the claimant (pediatric: less than 21 y, adult: 21 y or older). These groups were compared based on percentage of claims resulting in payment, indemnity paid, and years between occurrence of incident and filing of claim. In addition, the top 10 most prevalent claims were identified and compared between groups. A total of 25,702 closed orthopaedic claims were included. Pediatric claims accounted for 13% of the data. The average time from incident to claim filing was 1.92 years for pediatrics and 1.59 years for adults. Pediatric claims resulted in a higher percent of payment (33% vs. 30%) and average indemnity paid ($189,732 vs. $180,171) compared with adults. Five of the top 10 conditions resulting in a claim in each group were the same. Comparing these 5 conditions, in general there were minimal differences in the average time to claim filing between the groups, but larger average indemnity paid in the pediatric group. There appear to be moderate differences in outcomes of orthopaedic malpractice claims between adult and pediatric patients. The longer statute of limitations associated with pediatric claims does not appear to portend a less favorable medicolegal outcome or excessively longer time to claims filing for pediatric patients.


NLRP3-Induced NETosis: A Potential Therapeutic Target for Ischemic Thrombotic Diseases?
Ischemic thrombotic disease, characterized by the formation of obstructive blood clots within arteries or veins, is a condition associated with life-threatening events, such as stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism. The conventional therapeutic strategy relies on treatments with anticoagulants that unfortunately pose an inherent risk of bleeding complications. These anticoagulants primarily target clotting factors, often overlooking upstream events, including the release of neutrophil extracellular traps (NETs). Neutrophils are integral components of the innate immune system, traditionally known for their role in combating pathogens through NET formation. Emerging evidence has now revealed that NETs contribute to a prothrombotic milieu by promoting platelet activation, increasing thrombin generation, and providing a scaffold for clot formation. Additionally, NET components enhance clot stability and resistance to fibrinolysis. Clinical and preclinical studies have underscored the mechanistic involvement of NETs in the pathogenesis of thrombotic complications, since the clots obtained from patients and experimental models consistently exhibit the presence of NETs. Given these insights, the inhibition of NETs or NET formation is emerging as a promising therapeutic approach for ischemic thrombotic diseases. Recent investigations also implicate a role for the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome as a mediator of NETosis and thrombosis, suggesting that NLRP3 inhibition may also hold potential for mitigating thrombotic events. Therefore, future preclinical and clinical studies aimed at identifying and validating NLRP3 inhibition as a novel therapeutic intervention for thrombotic disorders are imperative.


Direct to Consumer Mobile Teledermatology Apps: An Exploratory Study.
Since 2012, "Direct to Consumer" mobile teledermatology apps have become more available, relinquishing many data collection tasks normally done by healthcare professionals directly to patients. To determine user friendliness, diagnostic quality, and service of commercially available mobile teledermatology apps. All mobile teledermatology apps available at the Apple App Store were reviewed. The two most popular mobile teledermatology apps were identified and tested together with three apps having similar functionality using a single case of a patient who was also examined by a dermatologist in-person. Apps varied in diagnostic scope, data gathering methods, services, rendered results, and in geographic coverage and cost. None of the apps take a history as thoroughly as recommended by textbooks. Key medical questions like current medications and allergies are not asked often. Most apps rendered concordant results, except for the one having the least thorough history taking. Mobile teledermatology application interfaces, services, and cost vary, with some risking medical errors and possible distribution of continuity of care. The American Telemedicine Association's guidelines for teledermatology need to address the use of direct to consumer apps. To protect consumers, app regulation, certification, or guidelines suggesting appropriate development and use might be considered.


Effect of bretylium on neuromuscular transmission.
The effect of bretylium on the response of an isolated muscle (guinea pig lumbrical) to direct and indirect stimulation was examined. An initial increase in twitch response to both indirect and direct stimulation was followed at higher concentrations of bretylium by block of the indirect response only. The ED50 for this latter effect was 106.9 +/- 9.25 microM. However, in the presence of subthreshold levels of d-tubocurarine the ED50 was markedly reduced to 1.31 +/- 1.11 microM, a concentration that could occur during clinical use of bretylium. Thus, the physician is cautioned to consider the possibility that neuromuscular block may be produced when bretylium is administered in close temporal proximity to neuromuscular blocking agents.


Cystic fibrosis mutation screening in CBAVD patients and men with obstructive azoospermia or severe oligozoospermia.
Congenital bilateral absence of the vas deferens (CBAVD) found in otherwise healthy infertile males, is associated with a high incidence of mutated cystic fibrosis transmembrane conductance regulator (CFTR) alleles, and is considered a genital form of cystic fibrosis (CF). The CF gene may also be involved in the aetiology of male infertility in cases other than CBAVD. The present study was undertaken to test the involvement of CFTR gene mutations in 14 CBAVD males and additionally in cases of male infertility caused by obstructive azoospermia (n = 10) and severe oligozoospermia (n = 3). The entire coding region of the CFTR gene was analysed using denaturing gradient gel electrophoresis (DGGE). The three allele (5T, 7T, 9T) polymorphic tract of thymidines in intron 8 (IVS8-polyT) of which the 5T allele acts as a mild mutation, causing reduced levels of normal CFTR mRNA due to deletion of exon 9, was also analysed. Of the 14 CBAVD cases, four (28.6%) were found to have mutations in both copies of the CFTR gene, six (42.8%) had one CFTR mutation, and in the remaining four (28.6%) no CFTR mutations were found. Of the 10 cases with obstructive azoospermia, three (30%) had one CFTR mutation and in the remaining seven (70%) no mutations were found. None of the three severe oligozoospermia cases carried a CFTR mutation. The frequency of the IVS8(5T) allele was 14.3% (4/28) for the CBAVD cases and 5% (1/20) for the obstructive azoospermia cases, none of the severe oligozoospermia males carried the IVS8-5(5T) allele. The data indicate that while there is a strong association between male infertility caused by CBAVD and mutations in the CFTR gene, cases of obstructive azoospermia without CBAVD also seem to be associated with CFTR gene mutations.


Structural investigation of GeSb6Te10 and GeBi6Te10 intermetallic compounds in the chalcogenide homologous series.
The crystal structures of GeSb(6)Te(10) and GeBi(6)Te(10) were scrutinized using an X-ray powder diffraction method, which revealed that these compounds crystallize in trigonally distorted cubic close-packed structures with a 51-layer period (R3m). Each layer consists of a triangular atomic net; Te atoms occupy their own specific layers, whereas Ge, Sb and Bi atoms are located in the other layers. In these pseudobinary compounds, random atomic occupations of Ge and Sb/Bi are observed and the layers form two kinds of elemental structural blocks by their successive stacking along the c axis. These compounds can be presumed to be isostructural. It is known that the chemical formula of the chalcogenide compounds with the homologous structures found in these pseudobinary systems can be written as (GeTe)(n)(Sb(2)Te(3))(m) or (GeTe)(n)(Bi(2)Te(3))(m) (n, m: integer); the GeSb(6)Te(10) and GeBi(6)Te(10) investigated in this study, which correspond to the case in which n = 1 and m = 3, naturally have 3 x l = 51-layer structures according to a formation rule l = 2n + 5m commonly found in the compounds of these chalcogenide systems (l represents the number of layers in the basic structural unit). Calculations based on the density functional theory revealed that these materials are compound semiconductors with very narrow band gaps.


Lesions in the sterol delta reductase gene of Arabidopsis cause dwarfism due to a block in brassinosteroid biosynthesis.
The brassinosteroid (BR) biosynthetic pathway, and the sterol pathway which is prerequisite to the BR pathway, are rapidly being characterized because of the availability of a large number of characteristic dwarf mutants in Arabidopsis. Here we show that the Arabidopsis dwarf5 mutants are disrupted in a sterol Delta7 reduction step. dwf5 plants display the characteristic dwarf phenotype typical of other BR mutants. This phenotype includes small, round, dark-green leaves, and short stems, pedicels, and petioles. Metabolite tracing with 13C-labeled precursors in dwf5 verified a deficiency in a sterol Delta7 reductase activity. All six independent alleles contain loss-of-function mutations in the sterol Delta7 reductase gene. These include a putative mRNA instability mutation in dwf5-1, 3' and 5' splice-site mutations in dwf5-2 and dwf5-6, respectively, premature stop codons in dwf5-3 (R400Z) and dwf5-5 (R409Z), and a mis-sense mutation in dwf5-4 (D257N). The dwf5 plant could be restored to wild type by ectopic overexpression of the wild-type copy of the gene. Both the Arabidopsis dwf5 phenotype and the human Smith-Lemli-Opitz syndrome are caused by loss-of-function mutations in a sterol Delta7 reductase gene, indicating that it is required for the proper growth and development of these two organisms.


Home-based exercise programmes for individuals with intermittent claudication: A protocol for an updated systematic review and meta-analysis.
The aim of this updated review is to consider the evidence base for the effectiveness of home-based exercise programmes as a treatment option for improving walking distance in patients with intermittent claudication. The Medline, EMBASE, CINAHL, PEDro and Cochrane CENTRAL databases will be searched for terms including 'intermittent claudication', 'peripheral arterial disease', 'home-based exercise' and 'home-based walking'. No date restrictions will be used but only articles in the English language will be included. Both randomised and non-randomised trials of home-based exercise programmes versus a comparator arm will be included, and a meta-analysis using only the randomised controlled trials will be attempted if the assumptions of heterogeneity are met. Data extraction will include study details, sample description, intervention description, length of follow-up and outcomes measures. The primary outcome measure is objectively measured maximal walking distance or time, with secondary outcome measures including pain-free walking distance or time, changes in physical activity and quality of life. We will also provide a narrative description of the effective components of a home-based exercise intervention which can aid future recommendations. Overall, this proposed review and meta-analysis aims provide a comprehensive and complete overview of the evidence base for home-based exercise programmes, which can aid clinicians in the management of their patients.


Ballistic exercise as a pre-activation stimulus: a review of the literature and practical applications.
Post-activation potentiation (PAP) refers to the acute enhancement of muscular function as a direct result of its contractile history. Protocols designed to elicit PAP have commonly employed heavy resistance exercise (HRE) as the pre-activation stimulus; however, a growing body of research suggests that low-load ballistic exercises (BE) may also provide an effective stimulus. The ability to elicit PAP without the need for heavy equipment would make it easier to utilise prior to competition. It is hypothesised that BE can induce PAP given the high recruitment of type II muscle fibres associated with its performance. The literature has reported augmentations in power performance typically ranging from 2 to 5 %. The performance effects of BE are modulated by loading, recovery and physical characteristics. Jumps performed with an additional loading, such as depth jumps or weighted jumps, appear to be the most effective activities for inducing PAP. Whilst the impact of recovery duration on subsequent performance requires further research, durations of 1-6 min have been prescribed successfully in multiple instances. The effect of strength and sex on the PAP response to BE is not yet clear. Direct comparisons of BE and HRE, to date, suggest a tendency for HRE protocols to be more effective; future research should consider that these strategies must be optimised in different ways. The role of acute augmentations in lower limb stiffness is proposed as an additional mechanism that may further explain the PAP response following BE. In summary, BE demonstrates the potential to enhance performance in power tasks such as jumps and sprints. This review provides the reader with some practical recommendations for the application of BE as a pre-activation stimulus.


Full-Endoscopic Oblique Lateral Lumbar Interbody Fusion: A Technical Note With 1-Year Follow-Up.
Oblique lateral lumbar interbody fusion (OLLIF) is a minimally invasive lumbar interbody fusion procedure using a bullet-shaped polyetheretherketone (PEEK) nonexpandable fusion cage modified to diminish risk to the exiting nerve root during posterolateral implantation through the Kambin safe zone under fluoroscopic guidance. The objective of this study was to present feasibility of this procedure and 1-year clinical outcome data. The authors present a prospective cohort study of 20 patients who underwent fluoroscopy-guided and full-endoscopic OLLIF in 22 segments allowing protection of the exiting nerve root from January 2018 to March 2019. The foraminoplasty, discectomy, endplate preparation, placement of bone graft and insertion of the fusion cage was done under continuous full-endoscopic visualization. The OLLIF fusion was backed up with bilateral percutaneous posterior supplemental pedicle screw fixation. Primary clinical outcome measures were the visual analog scale (VAS) of low back and leg pain, and Oswestry disability index (ODI) at 1 week, 3 months, 6 months, and 1 year after the operation. At final follow-up, the Macnab score was also evaluated. Secondary outcome measures were computed tomography (CT) assessment fusion using the Mannion classification of spinal fusion and adverse events related to the device as well as magnetic resonance imaging (MRI) assessment of nerve root decompression. All patients had significant relief of low back pain and leg pain, by VAS and ODI scores that improved significantly (P < .01). There were no complications. Postoperative lumbar MRI of all patients showed sufficient direct nerve decompression. At 1-year follow-up, excellent Macnab outcomes were obtained 13 patients, good in six, and fair in one. Impaired sensation and muscle strength of the involved nerve root significantly recovered in all but 2 patients (P < .05). According to the Mannion CT-based classification of spinal fusion, CT showed complete interbody fusion achieved in all 22 segments. Full-endoscopic OLLIF is a safe, effective, minimally invasive, economical, practical, and widely applicable minimally invasive interbody fusion technique in the lumbar spine. 3.


Motor memory and local minimization of error and effort, not global optimization, determine motor behavior.
Many real life tasks that require impedance control to minimize motion error are characterized by multiple solutions where the task can be performed either by co-contracting muscle groups, which requires a large effort, or, conversely, by relaxing muscles. However, human motor optimization studies have focused on tasks that are always satisfied by increasing impedance and that are characterized by a single error-effort optimum. To investigate motor optimization in the presence of multiple solutions and hence optima, we introduce a novel paradigm that enables us to let subjects repetitively (but inconspicuously) use different solutions and observe how exploration of multiple solutions affect their motor behavior. The results show that the behavior is largely influenced by motor memory with subjects tending to involuntarily repeat a recent suboptimal task-satisfying solution even after sufficient experience of the optimal solution. This suggests that the CNS does not optimize co-activation tasks globally but determines the motor behavior in a tradeoff of motor memory, error, and effort minimization.


Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task.
Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with (15)O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.


[Features of thermogenesis in newborn rats].
The millicalorimetry technique with simultaneous recording of the EMG and of the rectal and brown fat tissue temperatures revealed the energy contributions of motor activity and of brown fat to total heat production in newborn rats of 3-4 and 8-9-day age. In absence of motor activity no increase of heat production occurs. In 3-4-day old rats, the heat production per unit of motor activity in greater than in 8-9-day old rats. Nevertheless, as the result of more intense movements, the 8-9-day old rats handle better a moderate cold stress: their rectal temperature proved higher by 1.3 degrees than in the 3-4-day old rats.


Annual performance analysis and comparison of pellet production integrated with an existing combined heat and power plant.
Three optional pellet production processes integrated with an existing biomass-based CHP plant using different raw materials (wood chips and solid hydrolysis residues) are studied. The year is divided into 12 periods, and the integrated biorefinery systems are modeled and simulated for each period. The annual economic performance of three integrated biorefinery systems is analyzed based on the simulation results. The option of pellet production integrated with the existing CHP plant with the exhaust flue gas and superheated steam as drying mediums has the lowest specific pellet production cost of 105 €/t(pellet), the shortest payback time of less than 2 years and the greatest CO(2) reduction of the three options. An advantage in common among the three options is a dramatic increase of the total annual power production and significant CO(2) reduction in spite of a small decrease of power efficiency.


Temporal distribution of transmissible mink encephalopathy virus in mink inoculated subcutaneously.
Information was sought on the temporal distribution of transmissible mink encephalopathy virus in royal pastel mink inoculated subcutaneously with 10(3.0) 50% intracerebral lethal doses of the Idaho strain. As determined by intracerebral assay in mink, extremely little replication of the virus occurred during the preclinical stage of infection. It seemed largely limited to lymph nodes draining the site of inoculation. Virus first appeared in the central nervous system (CNS) at 20 weeks, when all mink were still clinically normal. Early spongiform degeneration, limited to the posterior sigmoid gyrus of the frontal cortex, was first found at 28 weeks, or a few weeks before onset of clinical disease in most of the mink. Once virus reached the CNS, where greater concentrations occurred than elsewhere, it appeared in many extraneural sites (spleen, liver, kidney, intestine, mesenteric lymph node, and submandibular salivary gland). These seemingly anomalous findings, especially the limited extraneural replication of virus as a prelude to infection of the CNS, suggest that mink are not natural hosts of the virus. The results of this study support the generally held view that transmissible mink encephalopathy arises from chance or inadvertent infection of ranch mink with an exogenous virus, most likely feed-borne wild scrapie virus.


How does dysautonomia influence the outcome of traumatic brain injured patients admitted in a neurorehabilitation unit?
Patients surviving severe traumatic brain injury (TBI) may suffer from symptoms presumed to be related to an excessive sympathetic production known as paroxysmal sympathetic hyperactivity (PSH). While this condition is more common in the acute phase, prognosis is less clear in rehabilitation settings. The goal of this study is to describe the functional status of patients with PSH admitted in a rehabilitation hospital and to determine its prognostic influence during rehabilitation. A cohort study was undertaken of all the patients admitted in a neurorehabilitation hospital suffering from PSH. Functional outcomes were reported according to the Glasgow outcome scale-extended (GOSE), the Disability Rating Scale (DRS) and the Functional Independence Measure (FIM). Thirteen out of 39 patients suffered symptoms compatible with PSH. Neuroimaging of PSH patients showed more diffuse lesions. The FIM at admission was lower in the PSH group who was transferred for rehabilitation at an earlier stage. At discharge no differences were seen using the FIM, DRS and GOS-E. Functional status is similar and PSH does not appear to influence recovery during the rehabilitation, although PSH patients are more likely to undergo psychoactive medications and special care is needed to approach their caregivers that perceive PSH as a complication for rehabilitation.


Building synthetic gene circuits from combinatorial libraries: screening and selection strategies.
The promise of wide-ranging biotechnology applications inspires synthetic biologists to design novel genetic circuits. However, building such circuits rationally is still not straightforward and often involves painstaking trial-and-error. Mimicking the process of natural selection can help us to bridge the gap between our incomplete understanding of nature's design rules and our desire to build functional networks. By adopting the powerful method of directed evolution, which is usually applied to protein engineering, functional networks can be obtained through screening or selecting from randomised combinatorial libraries. This review first highlights the practical options to introduce combinatorial diversity into gene circuits and then examines strategies for identifying the potentially rare library members with desired functions, either by screening or selection.


Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial.
Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the "Eplerenone in Primary Hyperparathyroidism" (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e', diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal pro-brain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted β-coefficient = 0.201, P = 0.035) and e' (β = 0.188, P = 0.042), respectively. OC (β = 0.192, P = 0.039) and BALP (β = 0.198, P = 0.030) were each independently related with e'. CTX showed no correlations with LVEF or e'. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies.


Prevalence and factors associated with cancellation and deferment of elective surgical cases at a rural private tertiary hospital in Western Uganda: a cross-sectional study.
the cancellation of elective surgery is still a worldwide challenge and this is associated with emotional and economical trauma for the patients and their families as well as a decrease in the efficiency of the operating theatre. This study aimed at determining the prevalence and factors associated with cancellation and deferment of elective surgery in a rural private tertiary teaching hospital in Western Uganda. a cross-sectional study design was conducted. Data was collected from 1st July 2019 to 31st December 2019. Patients scheduled for elective surgery and either cancelled or deferred on the actual day of surgery were included in the study. Statistical analysis was done using STATA version 15. four hundred patients were scheduled for elective surgery during the study period, among which 90 (22.5%) were cancelled and 310 (78.5%) had their surgeries as scheduled. The highest cancellation of elective surgical operations was observed in general surgery department with 81% elective cases cancelled or deferred, followed by orthopedic department 10% and gynecology department 9%. The most common reasons for cancellation were patient-related (39%) and health worker-related (35%) factors. Other factors included administrative (17%) and anesthesia related factors (9%). Cancellation was mainly due to lack of finances which accounted for 23.3% of the patients, inadequate patient preparation (16.6%) and unavailability of surgeons (15.5%). Major elective surgeries were cancelled 1.7 times more than minor electives surgeries [adjusted prevalence ratio 1.7 (95%CI: 1.07-2.73) and p-value: 0.024]. cancellation and deferment of elective surgeries is still of a major concern in this private rural tertiary hospital with most of the reasons easily preventable through proper scheduling of patients, improved communication between surgical teams and with patients; and effective utilization of available resources and man power.


Effects of climate-induced increases in summer drought on riparian plant species: a meta-analysis.
1. Frequency and duration of summer droughts are predicted to increase in the near future in many parts of the world, with considerable anticipated effects on riparian plant community composition and species richness. Riparian plant communities along lowland streams are characterised by high species richness due to their system-specific environmental gradients. As these streams and their hydrological gradients are mainly rain-fed, they are sensitive to precipitation changes. 2. We conducted a literature survey and meta-analysis to examine the effects of an increase in summer drought on: (i) riparian plant biomass; (ii) riparian seedling survival and (iii) riparian plant species composition and richness. We also aimed to determine whether hydrological thresholds related to drought tolerance can be distinguished for riparian plant species. 3. ISI Web of Knowledge was searched for relevant peer-reviewed studies, and 23 papers were found that met our criteria and contained quantitative study results. To detect overall responses of biomass and seedling survival, a random-effects model was applied using Comprehensive Meta-analysis™ software. Regression curves were then fitted to response ratio data relating the effects on drought-impacted groups to those on control groups. 4. Our results showed that a drought duration of approximately >30 days strongly reduces riparian plant biomass and that a duration of approximately >30-35 days and high drought intensities (starting from 3 to 4 cm water table decline per day) can be detrimental for riparian seedling survival. Especially Populus and Salix seedlings showed a reduced survival in response to drought, in contrast to Tamarix seedlings, which have the ability to rapidly and expansively elongate their roots. The data also revealed that an increase in drought conditions rapidly leads to a decline of riparian species richness and an increased presence of species adjusted to drier conditions. 5. Riparian groundwater level, surface water permanence and certain plant traits, especially plasticity in rooting depth, were mentioned most frequently as factors determining species responses. Very few studies mentioned hydrological thresholds, such as critical values for ground- and/or surface water levels, and so far these results have proved difficult to generalise. 6. Our meta-analysis has shown that the projected increase in the duration and intensity of drought periods, especially intense droughts lasting more than 30 days, can be expected to narrow the riparian wetland zone with typical hydric species and accelerate riparian wetland species losses in the near future. This may require extra efforts in terms of management and restoration of species-rich riparian areas.


Cementum-like matrix in solitary bone cysts: a unique and characteristic but yet underrecognized feature of promising diagnostic utility.
Solitary bone cysts (SBCs) are benign, intraosseus, cystic lesions, which generally involve metaphysis of long bones during the period of skeletal immaturity. Histologic features are nonspecific, but identification of amorphous cementum-like material provides a significant diagnostic clue. This material is unique to SBC with reported frequency of 10% to 70% and has been described as an immature form of bone. We retrieved and reviewed 41 cases of SBC reported in the last 10 years. The ages of patients ranged from 4 to 64 years (mean, 16 years), with a male-to-female ratio of 3:1. Humerus and femur were the most common sites. Cementum-like matrix was observed in 26 cases (63.4%). This material was seen in different phases of deposition and progression, ultimately transforming into mature bone as seen in 4 cases. Cyst wall lining was observed in 70.7% of cases along with several other nonspecific histologic features including reactive bone formation, hemosiderin macrophages, hemorrhage, multinucleated giant cells, foamy macrophages, fibrin, cholesterol clefts, and granulation tissue. Cementum-like material in the wall of SBCs is a specific and fairly consistent finding of diagnostic significance in cases where cyst wall lining is deficient. We also histologically demonstrate, for the first time, transformation of cementum-like material into reactive and mature bone, which further validates the immature osteoid nature and finding of other authors.


Health Insurance Coverage and Access to Care by Sexual Orientation During the COVID-19 Pandemic: United States, January 2021-February 2022.
Objectives. To compare health insurance coverage and access to care by sex and sexual minority status during the COVID-19 pandemic and assess whether lack of insurance hindered access to care by sexual minority status. Methods. Using Behavioral Risk Factor Surveillance System data (January 2021-February 2022), we examined differences by sex and sexual orientation among 158 722 adults aged 18 to 64 years living in 34 states. Outcomes were health insurance coverage type and 3 access to care measures. Results. Sexual minority women were significantly more likely to be uninsured than were heterosexual women, and lack of insurance widened the magnitude of disparity by sexual minority status in all measures of access. Compared with heterosexual men with health insurance, sexual minority men with health insurance were significantly more likely to report being unable to afford necessary care. Conclusions. During the pandemic, 1 in 8 sexual minority adults living in 34 study states were uninsured. Among sexual minority women, lack of insurance widened inequities in access to care. There were inequities among sexual minority men with health insurance. Public Health Implications. Sexual minority adults may be disproportionately affected by the unwinding of the COVID-19 public health emergency and may require tailored efforts to mitigate insurance coverage loss. (Am J Public Health. 2024;114(1):118-128. https://doi.org/10.2105/AJPH.2023.307446).


Thapsigargin-induced endothelium-dependent triphasic regulation of vascular tone in the porcine renal artery.
1. To elucidate the role of thapsigargin-induced Ca2+ entry in endothelial cells in the regulation of vascular tone, changes in Ca2+ and force of smooth muscle were simultaneously monitored in fura-2-loaded strips of porcine renal artery. 2. During phenylephrine-induced sustained contraction, thapsigargin caused an endothelium-dependent triphasic response; an initial relaxation, a subsequent transient contraction, and a sustained relaxation. The initial relaxation and the contraction were associated with a decrease and an increase in [Ca2+]i, respectively. There was no apparent [Ca2+]i decrease during the sustained relaxation. Thapsigargin-induced responses were observed at 10-8 M and higher concentrations, with the maximum response observed at 10-6 M. 3. The transient contraction was inhibited by a cyclo-oxygenase inhibitor (10-5 M indomethacin), a thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708), and a TXA2 synthase inhibitor (10-5 M OKY-046). 4. During the phenylephrine-induced contraction in the presence of indomethacin, thapsigargin caused an initial, but not a sustained relaxation, in the presence of Nomega-nitro-L-arginine methylester (L-NAME). During the contraction induced by phenylephrine plus 40 mM K+-depolarization in the presence of indomethacin, thapsigargin induced both a transient and a sustained relaxation. However, these relaxations were completely abolished in the presence of L-NAME. 5. Thapsigargin caused a large Ca2+ elevation in cultured endothelial cells of the renal artery. The concentration-response relation was thus similar to that for force development in the arterial strips. 6. In conclusion, thapsigargin-induced Ca2+ entry in endothelial cells led to triphasic changes in the tone of the porcine renal artery. The endothelium-dependent contraction was mediated mainly by TXA2. Nitric oxide and hyperpolarizing factor are both involved in the initial relaxation. However, a sustained relaxation was observed which mainly depended on nitric oxide.


Exceptional Human Longevity.
Exceptional longevity represents an extreme phenotype. Current centenarians are survivors of a cohort who display delayed onset of age-related diseases and/or resistance to otherwise lethal illnesses occurring earlier in life. Characteristics of aging are heterogeneous, even among long-lived individuals. Associations between specific clinical or genetic biomarkers exist, but there is unlikely to be a single biomarker predictive of long life. Careful observations in the oldest old offer some empirical strategies that favor increased health span and life span, with implications for compression of disability, identification and implementation of lifestyle behaviors that promote independence, identification and measurement of more reliable markers associated with longevity, better guidance for appropriate health screenings, and promotion of anticipatory health discussions in the setting of more accurate prognostication. Comprehensive PubMed literature searches were performed, with an unbiased focus on mechanisms of longevity. Overall, the aggregate literature supports that the basis for exceptional longevity is multifactorial and involves disparate combinations of genes, environment, resiliency, and chance, all of which are influenced by culture and geography.


Studies on the structure of hyaluronic acid. Characterization of the product formed when hyaluronic acid is treated with ascorbic acid.
Physical and chemical methods were used to characterize hyaluronic acid before (fraction HAIIBI) and after (fraction HA-AA) treatment with ascorbic acid. Fraction HA-AA was recovered with an almost quantitative yield and was shown to be chemically identical with fraction HAIIBI by all the methods used. These two materials, however, differed markedly in their molecular sizes and degree of polydispersity. By using sedimentation, diffusion and sedimentation-equilibrium analyses, weight-average molecular weights of about 1.2x10(6) and 6.5x10(4) respectively were obtained for fractions HAIIBI and HA-AA. It is concluded from these results that hyaluronic acid has a molecular weight of about 65000 and that the polysaccharide chain of this molecule is not depolymerized by ascorbic acid. It is further proposed that hyaluronic acid molecules in the matrix of connective tissues are present either in an aggregated form or as subunits of heterogeneous macromolecules, and that it is the linkages responsible for the organization of these structures which are broken by ascorbic acid.


Coupled temperature and γ-radiation effect on silica-based optical fiber strain sensors based on Rayleigh and Brillouin scatterings.
Coupled temperature and γ-ray influence on Brillouin (PPP-BOTDA) and Rayleigh (TW-COTDR) scatterings are quantified. Aging tests of these distributed strain measuring systems are performed on-line, up to 1 MGy, at room temperature, 80 ∘C, 100 ∘C and 120 ∘C. Brillouin and Rayleigh frequency shifts remain identical regardless of the temperature: 3 MHz (2 MHz) and 7 GHz (3 GHz) for Ge-doped (respectively F-doped) fiber at 1 MGy. Meanwhile, radiation-induced attenuation is diminished because of the higher temperature; hence, the maximal distance range is less deteriorated. These tests help to explain the origin of the Brillouin frequency shift under γ-rays, with an acoustic velocity variation of about 1 m/s in 1 MGy irradiated samples.


Assessing the contextual effect of community in the utilization of postnatal care services in Ghana.
Inequalities in the use of postnatal care services (PNC) in Ghana have been linked to poor maternal and neonatal health outcomes. This has ignited a genuine concern that PNC interventions with a focus on influencing solely individual-level risk factors do not achieve the desired results. This study aimed to examine the community-level effect on the utilization of postnatal care services. Specifically, the research explored clusters of non-utilization of PNC services as well as the effect of community-level factors on the utilization of PNC services, with the aim of informing equity-oriented policies and initiatives. The 2014 Ghana Demographic and Health Survey GDHS dataset was used in this study. Two statistical methods were used to analyze the data; spatial scan statistics were used to identify hotspots of non-use of PNC services and second two-level mixed logistic regression modeling was used to determine community-level factors associated with PNC services usage. This study found non-use of PNC services to be especially concentrated among communities in the Northern region of Ghana. Also, the analyses revealed that community poverty level, as well as community secondary or higher education level, were significantly associated with the utilization of PNC services, independent of individual-level factors. In fact, this study identified that a woman dwelling in a community with a higher concentration of poor women is less likely to utilize of PNC services than those living in communities with a lower concentration of poor women (Adjusted odds ratio (AOR) = 0.60, 95%CI: 0.44-0.81). Finally, 24.0% of the heterogeneity in PNC services utilization was attributable to unobserved community variability. The findings of this study indicate that community-level factors have an influence on women's health-seeking behavior. Community-level factors should be taken into consideration for planning and resource allocation purposes to reduce maternal health inequities. Also, high-risk communities of non-use of obstetric services were identified in this study which highlights the need to formulate community-specific strategies that can substantially shift post-natal use in a direction leading to universal coverage.


Transfer of Escherichia coli to water from drained and undrained grassland after grazing.
The aim of this study was to determine the load of Escherichia coli transferred via drainage waters from drained and undrained pasture following a grazing period. Higher concentrations (ranging between 10(4) and 10(3) colony forming units [CFU] g(-1)) of E. coli persisted in soil for up to 60 d beyond the point where cattle were removed from the plots, but these eventually declined in the early months of spring to concentrations less than 10(2) CFU g(-1). The decline reflects the combined effect of cell depletion from the soil store through both wash-out and die-off of E. coli. No difference (P > 0.05) was observed in E. coli loads exported from drained and undrained plots. Similarly, no difference (P > 0.05) was observed in E. coli concentrations in drainage waters of mole drain flow and overland plus subsurface interflow. Intermittent periods of elevated discharge associated with storm events mobilized E. coli at higher concentrations (e.g., in excess of 400 CFU mL(-1)) than observed during low flow conditions (often <25 CFU mL(-1)). The combination of high discharge and cell concentrations resulted in the export of E. coli loads from drained and undrained plots exceeding 10(6) CFU L(-1) s(-1). The results highlight the potential for drained land to export E. coli loads comparable with those transferred from undrained pasture.


Confidence in COVID-19 vaccines moderates the association between vaccination status and mental distress.
Previous research has demonstrated that becoming vaccinated with the Coronavirus vaccine may lower mental distress. However, it remains uncertain whether this relationship holds amid concerns of vaccine side effects and doubts of the vaccine's protective capabilities. We presented three studies that showed how vaccine confidence negatively influences the relationship between vaccine uptake and mental distress. Using two-way fixed effects regression models, Study 1 analyzes longitudinal survey of respondents from Los Angeles County in the US, while Study 2 uses the same analytical strategy but generalises findings by analysing longitudinal data of participants across all 50 US states. Main results of both studies show that (i) vaccination uptake is linked with reduced mental distress among individuals with high vaccine confidence (ii) vaccine uptake has no effect on mental distress among individuals with low vaccine confidence. Lastly, Study 3 applies multilevel analysis to a large-scale pseudo-panel study of 15 developed countries. Results for the third study corroborate finding (i) but not (ii) in that the multinational study finds that vaccine uptake is actually associated with higher mental distress among individuals with low vaccine confidence. In sum, our paper shows that the palliative effect of vaccination on mental health only exists when vaccine confidence is high. Results are mixed on whether vaccination affects mental distress when individual vaccine confidence is low.


Functional redundancy of genes for sulphate activation enzymes in Rhizobium sp. BR816.
The broad-host-range, heat-tolerant Rhizobium strain BR816 produces sulphated Nod metabolites. Two ORFs highly homologous to the Sinorhizobium meliloti nodPQ genes were isolated and sequenced. It was found that Rhizobium sp. BR816 contained two copies of these genes; one copy was localized on the symbiotic plasmid, the other on the megaplasmid. Both nodP genes were interrupted by insertion of antibiotic resistance cassettes, thus constructing a double nodP1P2 mutant strain. However, no detectable differences in Nod factor TLC profile from this mutant were observed as compared to the wild-type strain. Additionally, plant inoculation experiments did not reveal differences between the mutant strain and the wild-type. It is proposed that a third, functionally homologous locus complements mutations in the Nod factor sulphation genes. Southern blot analysis suggested that this locus contains genes necessary for the sulphation of amino acids.


New therapeutic options for acromegaly.
Acromegaly is a slowly developing disfiguring disease characterized by chronic growth hormone (GH) and insulin-like growth factor-I (IGF-I) excess and caused by a pituitary somatotroph adenoma. It is associated to 2- to 3 fold increased mortality, compared to normal population, mostly due to cardiovascular and cerebro-vascular diseases, and to several co-morbid systemic illnesses, such as diabetes mellitus, hypertension, severe arthropathies, a specific cardio-myopathy, goitre, sleep-apnoea, intractable headache. The morbidity and excess mortality of acromegaly are usually the consequence of the metabolic actions of excess GH and IGF-I secretion, while only in rare patients mortality is due to the mass effects of the pituitary tumour. Since, serum IGF-I concentrations within age-adjusted normal range, and a tight GH control have to be achieved to normalize life-expectancy in these patients, an aggressive, and often multi-modality treatment is required for acromegaly. In recent years, new drugs, and new formulations of old drugs, have been developed that are able to effectively inhibit GH secretion or GH action, and may represent important adjuncts or even alternatives to the traditional approaches of surgery and radiotherapy. This review briefly summarizes the therapeutic options nowadays available for acromegaly. A brief note about innovative drugs under study, is also given.


Comparison of sun protection factors obtained with a xenon solar simulator and an Ultravitalux lamp.
The influence of the type of UV source on the sun protection factor (SPF) was investigated in healthy volunteers with skin Types I to III. In an open-paired comparison, sunscreens with low, medium and high SPF were examined under identical test conditions using either a 150-watt xenon-arc solar simulator or a set of four 300-watt Osram Ultravitalux bulbs as the UV source. Despite wide differences in the spectral output of the two sources, both yielded similar mean SPF for each of the three test sunscreens. The only significant difference observed was with the FRG standard, for which a lower mean SPF (3.1) was obtained with the Ultravitalux lamps compared to the solar simulator (mean SPF 4.0). There were no differences between the calculated arithmetic and geometric means.


Compassionate acts and everyday emotional well-being among newlyweds.
Compassion is deeply prized in Western marriages yet its benefits for emotional well-being have been investigated empirically only rarely. This research examined the association between compassionate acts and everyday emotional well-being in 175 newlywed couples. Following prior research and theory, we defined compassionate acts as caregiving that is freely given, focused on understanding and genuine acceptance of the other's needs and wishes, and expressed through openness, warmth, and a willingness to put a partner's goals ahead of one's own. We adopted an explicitly dyadic perspective so that we could consider how compassionate acts as well as their recognition influence the affective state of both donors and recipients. Our findings, which controlled for the general affective tone of marital interaction, revealed that compassionate acts are beneficial for both donors and recipients, and that the effects on the donor are stronger than the effects on the recipient. Moreover, we found that whereas recipients' benefits depend on their noticing the donors' actions, donors benefit regardless of whether the recipients explicitly notice the compassionate acts. The pattern of results for husbands and wives was very similar. These results suggest that in terms of emotional well-being, for donors, acting compassionately may be its own reward. (PsycINFO Database Record


Programmed death 1 regulates development of central memory CD8 T cells after acute viral infection.
The T cell response possesses a number of inhibitory receptors to regulate the extent of the antiviral response and prevent immune pathology. These receptors are generally transiently upregulated during an effector response and then downregulated during memory. Some inhibitory receptors, such as programmed death 1 (PD-1) and LAG-3, were shown to be aberrantly upregulated during memory to chronic lymphocytic choriomeningitis virus infection, limiting functional capabilities. However, little is known about the impact of inhibitory receptors on memory development during a normal CD8 T cell response to acute virus infection. Our previous data showed that PD-1 is aberrantly upregulated during a secondary response by memory CD8 T cells that were generated without CD4 T cell help. Therefore, we examined the role of PD-1 in memory differentiation during acute vaccinia virus infection in intact mice. In the absence of PD-1, the primary and memory CD8 T cell responses were enhanced. Moreover, there were distinct phenotypic and functional changes in the memory PD-1(-/-) CD8 T cells. Higher levels of CD62L, CD27, and CCR7 were detected; cells produced more IL-2 and made an enhanced secondary response. These changes indicate a skewing of the memory population toward the central memory phenotype in the absence of PD-1 signaling.


Human regulatory T cells undergo self-inflicted damage via granzyme pathways upon activation.
Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion of healthy, suppressive Tregs ex vivo and in vivo following the transfer. In clinical studies, levels of transferred Tregs decline sharply in the blood within a few days of the transfer. Tregs have a high rate of apoptosis. Here, we describe a new mechanism of Treg self-inflicted damage. We show that granzymes A and -B (GrA and GrB), which are highly upregulated in human Tregs upon stimulation, leak out of cytotoxic granules to induce cleavage of cytoplasmic and nuclear substrates, precipitating apoptosis in target cells. GrA and GrB substrates were protected from cleavage by inhibiting granzyme activity in vitro. Additionally, we show - by using cytometry by time of flight (CYTOF) - an increase in GrB-expressing Tregs in the peripheral blood and renal allografts of transplant recipients undergoing rejection. These GrB-expressing Tregs showed an activated phenotype but were significantly more apoptotic than non-GrB expressing Tregs. This potentially novel finding improves our understanding of Treg survival and suggests that manipulating Gr expression or activity might be useful for designing more effective Treg therapies.


Patient-specific workup of adrenal incidentalomas.
: To develop a clinical prediction model to predict a clinically relevant adrenal disorder for patients with adrenal incidentaloma. : This retrospective study is approved by the institutional review board, with waiver of informed consent. Natural language processing is used for filtering of adrenal incidentaloma cases in all thoracic and abdominal CT reports from 2010 till 2012. A total of 635 patients are identified. Stepwise logistic regression is used to construct the prediction model. The model predicts if a patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland at the moment of initial presentation, thus generates a predicted probability for every individual patient. The prediction model is evaluated on its usefulness in clinical practice using decision curve analysis (DCA) based on different threshold probabilities. For patients whose predicted probability is lower than the predetermined threshold probability, further workup could be omitted. : A prediction model is successfully developed, with an area under the curve (AUC) of 0.78. Results of the DCA indicate that up to 11% of patients with an adrenal incidentaloma can be avoided from unnecessary workup, with a sensitivity of 100% and specificity of 11%. : A prediction model can accurately predict if an adrenal incidentaloma patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland based on initial imaging features and patient demographics. However, with most adrenal incidentalomas labeled as nonfunctional adrenocortical adenomas requiring no further treatment, it is likely that more patients could be omitting from unnecessary diagnostics.


Correlation of haemodynamics and ankle mobility with clinical classes of clinical, aetiological, anatomical and pathological classification in venous disease.
To correlate venous haemodynamic parameters of lower limbs and amplitude of ankle mobility with the clinical, aetiological, anatomical and pathological classification (CEAP) for venous disease. Two hundred and eighty-four lower limbs of 142 Caucasian women were evaluated and distributed in six groups according to the CEAP classification: Group I = C0 and C1 (n = 24); Group II = C2 (n = 30); Group III = C3 (n = 27); Group IV = C4 (n = 23); Group V = C5 (n = 20) and Group VI = C6 (n = 18). Goniometric examinations of ankle joints and air plethysmography (APG) were performed. Analysis of variance and the Bonferroni correction, Kruskal-Wallis' non-parametric and Dunn tests were utilized for statistical analysis with the level of significance being set at 5% (P value < 0.05). There were significant restrictions in ankle mobility seen by goniometry at the C5 stage. In addition, significant changes in the venous-filling index were identified at C2, changes in the ejection fraction at C4 and changes in the residual volume fraction at the C4 stage. The evolution of the clinical state of ankles affected by venous diseases is correlated to a reduction of joint mobility and haemodynamic alterations identified using APG.


Drug utilization evaluation of imipenem and intravenous ciprofloxacin in a teaching hospital.
Drug Utilization Evaluation (DUE) studies are designed to assess drug usage appropriateness. We aim to evaluate the drug utilization of intravenous ciprofloxacin and imipenem, two of the broad spectrum antibiotics that consume a significant proportion of our hospitals' outlay, in different wards of a teaching hospital in Zabol. During a 5 months period (December 2010 to May 2011), 263 patients who received imipenem or intravenous ciprofloxacin were assigned to this study. Retrospective review of patient's records was carried out. Data were converted to Defined Daily Dose (DDD) and the ratio of prescribed daily dose per DDD was calculated. Among these records, 100 patients received either imipenem or ciprofloxacin. The ratio of prescribed daily dose to DDD was 1.5 for both antibiotics. Almost all patients received empiric therapy in both groups. Only 13 patients (26%) in ciprofloxacin group and 4 patients (8%) in imipenem group received their antibiotics consistent with American Hospital Formulary System (AHFS) mentioned indication. Baseline Blood Urea Nitrogen (BUN) and serum Creatinine were ordered for only 37 patients (74%) in both groups with 15 abnormal results but dose adjustment performed just in one case with decreased renal function. In conclusion, the majority of courses with both drugs were empirically selected and continued and required lab tests for drug monitoring and dose adjustments were not performed in most cases. Educational interventions, developing a local formulary and a strict antibiotic prescribing policy for example by prior approval by an infectious disease consultant can help significantly to overcome these problems.


Mind-Body Therapies and Osteoarthritis of the Knee.
Osteoarthritis of the knee is a major cause of disability among adults worldwide. Important treatment options include nonpharmacologic therapies, and especially symptom management strategies in which patients take an active role. Among these, mind-body therapies may have particular promise for alleviating the distressful symptoms associated with osteoarthritis of the knee. However, systematic reviews are lacking. The objective of this paper is to review English-language articles describing clinical studies evaluating the effects of patient-driven mind-body therapies on symptoms of knee osteoarthritis. Eight studies, representing a total of 267 participants, met the inclusion criteria. Interventions included tai chi, qigong, and yoga. Collectively, these studies suggest that specific mind-body practices may help alleviate pain and enhance physical function in adults suffering from osteoarthritis of the knee. However, sample sizes are small, rigorous investigations are few, and the potential benefits of several mind-body therapies have not yet been systematically tested. Additional high-quality studies are needed to clarify the effects of specific mind-body therapies on standardized measures of pain, physical function, and related indices in persons with osteoarthritis of the knee, and to investigate possible underlying mechanisms.


Dehydration-induced earthquakes identified in a subducted oceanic slab beneath Vrancea, Romania.
Vrancea, Eastern Romania, presents a significant intermediate-depth seismicity, between 60 and 170 km depth, i.e. pressures from 2 to 6.5 GPa. A debate has been lasting for decades regarding the nature of the seismic volume, which could correspond to the remnant of a subducted slab of Tethyan lithosphere or a delamination of the Carpathians lithosphere. Here we compile the entire seismicity dataset (≈ 10,000 events with 2 ≤ Mw ≤ 7.9) beneath Vrancea for P > 0.55 GPa (> 20 km) since 1940 and estimate the pressure and temperature associated with each hypocenter. We infer the pressure and temperature, respectively, from a depth-pressure conversion and from the most recent tomography-based thermal model. Pressure-temperature diagrams show to what extent these hypocentral conditions match the thermodynamic stability limits for minerals typical of the uppermost mantle, oceanic crust and lower continental crust. The stability limits of lawsonite, chloritoid, serpentine and talc minerals show particularly good correlations. Overall, the destabilization of both mantle and crustal minerals could participate in explaining the observed seismicity, but mantle minerals appear more likely with more convincing correlations. Most hypocentral conditions match relatively well antigorite dehydration between 2 and 4.5 GPa; at higher pressures, the dehydration of the 10-Å phase provides the best fit. We demonstrate that the Vrancea intermediate-depth seismicity is evidence of the current dehydration of an oceanic slab beneath Romania. Our results are consistent with a recent rollback of a W-dipping oceanic slab, whose current location is explained by limited delamination of the continental Moesian lithosphere between the Tethyan suture zone and Vrancea.


[3H]Ouabain binding and Na+, K+-ATPase in resealed human red cell ghosts.
The interaction of the cardiac glycoside [3H]ouabain with the Na+, K+ pump of resealed human erythrocyte ghosts was investigated. Binding of [3H]ouabain to high intracellular Na+ ghosts was studied in high extracellular Na+ media, a condition determined to produce maximal ouabain binding rates. Simultaneous examination of both the number of ouabain molecules bound per ghost and the corresponding inhibition of the Na+, K+-ATPase revealed that one molecule of [3H]ouabain inhibited one Na+, K+-ATPase complex. Intracellular magnesium or magnesium plus inorganic phosphate produced the lowest ouabain binding rate. Support of ouabain binding by adenosine diphosphate (ADP) was negligible, provided synthesis of adenosine triphosphate (ATP) through the residual adenylate kinase activity was prevented by the adenylate kinase inhibitor Ap5A. Uridine 5'-triphosphate (UTP) alone did not support ouabain binding after inhibition of the endogenous nucleoside diphosphokinase by trypan blue and depletion of residual ATP by the incorporation of hexokinase and glucose. ATP acting solely at the high-affinity binding site of the Na+, K+ pump (Km approximately 1 microM) promoted maximal [3H]ouabain binding rates. Failure of 5'-adenylyl-beta-gamma-imidophosphate (AMP-PNP) to stimulate significantly the rate of ouabain binding suggests that phosphorylation of the pump was required to expose the ouabain receptor.


A dose-ranging study of behavioral and pharmacological treatment in social settings for children with ADHD.
Placebo and three doses of methylphenidate (MPH) were crossed with 3 levels of behavioral modification (no behavioral modification, NBM; low-intensity behavioral modification, LBM; and high-intensity behavior modification, HBM) in the context of a summer treatment program (STP). Participants were 48 children with ADHD, aged 5-12. Behavior was examined in a variety of social settings (sports activities, art class, lunch) that are typical of elementary school, neighborhood, and after-school settings. Children received each behavioral condition for 3 weeks, order counterbalanced across groups. Children concurrently received in random order placebo, 0.15 mg/kg/dose, 0.3 mg/kg/dose, or 0.6 mg/kg/dose MPH, 3 times daily with dose manipulated on a daily basis in random order for each child. Both behavioral and medication treatments produced highly significant and positive effects on children's behavior. The treatment modalities also interacted significantly. Whereas there was a linear dose-response curve for medication in NBM, the dose-response curves flattened considerably in LBM and HBM. Behavior modification produced effects as large as moderate doses, and on some measures, high doses of medication. These results replicate and extend to social-recreational settings previously reported results in a classroom setting from the same sample (Fabiano et al., School Psychology Review, 36, 195-216, 2007). Results illustrate the importance of taking dosage/intensity into account when evaluating combined treatments; there were no benefits of combined treatments when the dosage of either treatment was high but combination of the low-dose treatments produced substantial incremental improvement over unimodal treatment.


Reciprocal roles of DBC1 and SIRT1 in regulating estrogen receptor α activity and co-activator synergy.
Estrogen receptor α (ERα) plays critical roles in development and progression of breast cancer. Because ERα activity is strictly dependent upon the interaction with coregulators, coregulators are also believed to contribute to breast tumorigenesis. Cell Cycle and Apoptosis Regulator 1 (CCAR1) is an important co-activator for estrogen-induced gene expression and estrogen-dependent growth of breast cancer cells. Here, we identified Deleted in Breast Cancer 1 (DBC1) as a CCAR1 binding protein. DBC1 was recently shown to function as a negative regulator of the NAD-dependent protein deacetylase SIRT1. DBC1 associates directly with ERα and cooperates synergistically with CCAR1 to enhance ERα function. DBC1 is required for estrogen-induced expression of a subset of ERα target genes as well as breast cancer cell proliferation and for estrogen-induced recruitment of ERα to the target promoters in a gene-specific manner. The mechanism of DBC1 action involves inhibition of SIRT1 interaction with ERα and of SIRT1-mediated deacetylation of ERα. SIRT1 also represses the co-activator synergy between DBC1 and CCAR1 by binding to DBC1 and disrupting its interaction with CCAR1. Our results indicate that DBC1 and SIRT1 play reciprocal roles as major regulators of ERα activity, by regulating DNA binding by ERα and by regulating co-activator synergy.


[The etiology of caries: the construction of a thought-style].
This study deals with the construction of the Odontological Thought Style about the etiology of caries. As a reference we use the theory of Ludwik Fleck (1896 -1961) maintaining that knowledge is a result of social activity and that each individual with certain knowledge belongs to a certain cultural environment, a thought-collective sharing the same thought-style. The sources used for studying the transformations in the theory were classic literature and a universe of 161 articles published between 1980 and 2001, selected from the Medline/Pubmed base using the key words dental caries/etiology/theoretical. Based on the analysis of these articles and books we identified a macro style of thinking characterized as multicausal-biologicist transforming the etiological knowledge mainly since the mid 90s. In this stage, in which the period of classicism of the theory does not respond any more to the reality of the disease revealed in epidemiological studies, five distinct trends could be identified: the biological; the clinical-biological; the clinical-epidemiological; the biopsychosocial and the social. Thus, one of the challenges posed to odontology today is to transform its thought-style adapting it to the new social reality of the disease.


Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass.
Although both of the small Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 have been demonstrated to play a role in chemotaxis, the precise and possible unique roles performed by each of these 2 Rac isoforms in neutrophil chemotaxis have not been defined. To elucidate the specific roles of Rac1 and Rac2 in neutrophils during the process of chemotaxis, we generated mice deficient in Rac1, Rac2, or in both Rac1 and Rac2 in cells of myeloid lineage including neutrophils by mating Rac2 null mice with mice carrying a conditional allele for Rac1 and expressing the Cre recombinase downstream of a specific myeloid promoter, lysozyme M. We demonstrate here that although Rac1 null neutrophils display normal chemokinesis, they are unable to migrate toward the source of the chemoattractant. By contrast, Rac2 null neutrophils can orient toward the chemoattractant source but are unable to migrate efficiently. We show that Rac1 is essential for gradient detection and orientation toward the chemoattractant source through spatially constrained regulation of phosphoinositol-3,4,5-trisphosphate (PIP(3)) and Akt in the leading edge and confirm that Rac2 is the primary regulator of actin assembly providing the molecular motor for neutrophil translocation during chemotaxis.


Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases.
Recent studies have shown that several loss-of-function mouse models of prostate carcinogenesis can develop a spectrum of precancerous lesions that resemble human prostatic intraepithelial neoplasia (PIN). Here, we have investigated the malignant potential of the high-grade PIN lesions that form in Nkx3.1(+/-); Pten(+/-) compound mutant mice and demonstrate their neoplastic progression in a serial transplantation/tissue recombination assay. Furthermore, we find that a majority of Nkx3.1(+/-); Pten(+/-) mice greater than 1 year of age develop invasive adenocarcinoma, which is frequently accompanied by metastases to lymph nodes. Finally, we observe androgen independence of high-grade PIN lesions after androgen ablation of Nkx3.1(+/-); Pten(+/-) mice. We conclude that Nkx3.1(+/-); Pten(+/-) mice recapitulate key features of advanced prostate cancer and represent a useful model for investigating associated molecular mechanisms and for evaluating therapeutic approaches.


From induction to conduction: how intrinsic transcriptional priming of extrinsic neuronal connectivity shapes neuronal identity.
Every behaviour of an organism relies on an intricate and vastly diverse network of neurons whose identity and connectivity must be specified with extreme precision during development. Intrinsically, specification of neuronal identity depends heavily on the expression of powerful transcription factors that direct numerous features of neuronal identity, including especially properties of neuronal connectivity, such as dendritic morphology, axonal targeting or synaptic specificity, ultimately priming the neuron for incorporation into emerging circuitry. As the neuron's early connectivity is established, extrinsic signals from its pre- and postsynaptic partners feedback on the neuron to further refine its unique characteristics. As a result, disruption of one component of the circuitry during development can have vital consequences for the proper identity specification of its synaptic partners. Recent studies have begun to harness the power of various transcription factors that control neuronal cell fate, including those that specify a neuron's subtype-specific identity, seeking insight for future therapeutic strategies that aim to reconstitute damaged circuitry through neuronal reprogramming.


Toxicity and immunomodulatory efficacy of biosynthesized silver myconanosomes on pathogenic microbes and macrophage cells.
Silver myconanosomes prepared from Alternaria brassicae may exhibit potential antimicrobial and immunomodulatory activity due to their inimitable character. The prepared myconanosomes were characterized by using differential light scattering, zeta potential, UV-visible spectroscopy and transmission electron microscopic analyses. Mycologically produced AgNPs were found as spherical and irregular shaped measuring size range between 55.4 and 70.23 nm. The antimicrobicidal activity of these AgNPs against pathogenic microbes was evaluated by agar well diffusion method. Results showed that AgNPs inhibit the growth of various bacteria and fungi, which may be due to the disruption of cell membranes, leakage of cytoplasm and DNA degradation. Cytotoxicity analysis of AgNPs on cell lines revealed its dose dependent effect. Moreover, significant increase of intracellular reactive oxygen species was characterized in AgNPs treated cells after 4 h of incubation. Thus, AgNPs may have a significant advantage over conventional antibiotics as microorganisms are acquiring resistance against the broad range of available antibiotics.


Intrinsic material properties of the erythrocyte membrane indicated by mechanical analysis of deformation.
Deformation of the erythrocyte membrane by the micropipette technique permits analysis of intrinsic material characteristics of the membrane and provides a means to differentiate purely membrane factors from such extrinsic factors as surface area-to-volume ratio. Using small micropipettes (less than 0.5 microns radius) to deform cells, it is evident that the red cell membrane behaves like a solid for periods of time up to 5-10 min of sustained deformation; for long periods of strain, permanent deformations occur, indicative of the semi-solid structural character. In the time range in which the membrane behaves like a solid, the material is linearly elastic up to strains of 400%, implying a loose network structure in the membrane plane, and evaluation of the elastic parameter mu (mu for normal discocytes equals 7 x 10(-3) dynes/cm) suggests that the elements comprising the network may have a molecular weight of approximately that of the water-soluble membrane protein spectrin. Whether the network system is cross-linked or simply a polymer solution remains unanswered. Experimental data indicate that plastic flow of the membrane under conditions of protracted strain may lead to permanent deformation of the membrane, whereas uniform dilation of the membrane, requiring over 1000 times more energy than for plastic flow, results in membrane failure and lysis. Analyses of the data from larger micropipettes of limiting mean cylindrical diameter show their utility in evaluating extrinsic factors, e.g., surface area-to-volume relationships, which are related to the capability of the whole cell to form a new configuration with implicit resistance to total surface area change, as the cell enters narrow channels of the microcirculation. Thus, micropipettes with diameters in the 2.7-3.0-microns range can provide sensitive comparisons of cellular deformability of erythrocytes.


Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000-molecular-weight membrane protein shared by monocytes.
We have recently shown that human monocytes and U937 cells possess two molecular classes of Fc gamma receptor. One, a 72,000-mol-wt sialoglycoprotein, has high affinity for certain subclasses of human and murine monomeric IgG. The other is a 40,000-mol-wt protein (p40) with low affinity for monomeric IgG but with the capacity to bind IgG aggregates or IgG-coated particles. In the present study, a 40,000-mol-wt single chain protein, apparently identical to p40 from U937 cells, was isolated from surface-radioiodinated human platelets by affinity purification using a murine IgG2b monoclonal antibody to p40. This 40,000-mol-wt protein was not seen when control IgG2b or unrelated murine monoclonal antibodies were employed in place of anti-p40. The same 40,000-mol-wt protein was also recovered from an IgG-Sepharose affinity adsorbent, but not from ovalbumin-or myoglobin-Sepharose. The 72,000-mol-wt Fc gamma receptor of monocytes was not identified on platelets. Monoclonal anti-p40 and Fab fragments derived from this antibody blocked platelet aggregation by heat-aggregated human IgG, whereas a control murine IgG2b protein had little or no inhibitory effect at 500-1,000-fold higher concentrations. A murine IgG1 monoclonal antibody, reactive with an unrelated platelet-specific membrane antigen, did not inhibit platelet responses to aggregated IgG. Anti-p40 did not affect platelet aggregation by thrombin, collagen, or fibrinogen plus ADP. Although anti-p40 did not directly aggregate platelets in the concentrations employed, cross-linking with F(ab')2 goat anti-murine Ig induced apyrase-sensitive aggregation of anti-p40-treated platelets. This indicates that p40 possesses transmembrane linkage for platelet activation and secretion. These observations strongly suggest that this newly recognized 40,000-mol-wt platelet membrane protein serves as an Fc gamma receptor.