Sustained release of hydrogen sulfide from anisotropic ferrofluid hydrogel for the repair of spinal cord injury.
Spinal cord injury (SCI) results in massive neuronal death, axonal disruption, and cascading inflammatory response, which causes further damage to impaired neurons. The survived neurons with damaged function fail to form effective neuronal circuits. It is mainly caused by the neuroinflammatory microenvironment at injury sites and regenerated axons without guidance. To address this challenge, a ferrofluid hydrogel (FFH) was prepared with Ferric tetrasulfide (Fe3S4), carboxymethyl chitosan, and gold. Its internal structural particles can be oriented in a magnetic field to acquire anisotropy. Moreover, Fe3S4 can release hydrogen sulfide (H2S) with anti-inflammatory effects under acidic conditions. Regarding in vitro experiments, 0.01g/ml Fe3S4 FFH significantly reduced the inflammatory factors produced by LPS-induced BV2 cells. Oriented and longer axons of the induced neural stem cells loaded on anisotropic FFH were observed. In vivo experiments showed that FFH reduced the activated microglia/macrophage and the expression of pro-inflammatory factors in SCI rats through the NF-κB pathway. Moreover, it significantly promoted directional axonal regrowth and functional recovery after SCI. Given the critical role of inhibition of neuroinflammation and directional axonal growth, anisotropic Fe3S4 FFH is a promising alternative for the treatment of SCI.


Induction of antigen presentation by macrophages after phagocytosis of tumour apoptotic cells.
Due to their resistance to classical chemotherapies, most human colorectal cancers have a high incidence and a poor prognosis. Immunotherapy using interleukin 2 (IL2) has provided disappointing results in the treatment of these cancers. Recently, however, we have demonstrated that a treatment combining a cell-differentiating agent, sodium butyrate (NaBut) with IL2 resulted in a remission of established peritoneal colorectal carcinomatosis in rats. Separately, neither NaBut nor IL2 treatment cured these tumour-bearing rats. NaBut is known to induce cell differentiation and subsequent apoptosis in epithelial cells, while IL2 stimulates the immune cells capable of participating in tumour rejection. We postulated that the significant therapeutic effect of NaBut/IL2 treatment could be attributed to a NaBut-induced increase in the immunogenicity of the cancer cells. We report here that NaBut induced an apoptotic process in rat colon tumour cells in vivo and in vitro. We observed, in an efficient cure, colocalization of apoptotic bodies and monocytes/macrophages at the periphery of the tumour. We propose that these apoptotic bodies are phagocytosed in vivo by the macrophages. We also showed in vitro that a subpopulation of macrophages involved in the phagocytic clearance of apoptotic cells expresses cell surface molecules associated with antigen presentation and stimulates the proliferation of naive splenocytes. Our data suggest that therapies that recruit massive induction of the apoptotic process in tumour cells could favour tumour antigen presentation via their specific phagocytosis by antigen-presenting cells (APCs). We propose that the development of specific therapies that stimulate both tumour cell apoptosis and the immune system could offer new opportunities in anti-cancer treatments of poorly immunogenic cancer cells.


Radiomics in breast MRI: current progress toward clinical application in the era of artificial intelligence.
Breast magnetic resonance imaging (MRI) is the most sensitive imaging modality for breast cancer diagnosis and is widely used clinically. Dynamic contrast-enhanced MRI is the basis for breast MRI, but ultrafast images, T2-weighted images, and diffusion-weighted images are also taken to improve the characteristics of the lesion. Such multiparametric MRI with numerous morphological and functional data poses new challenges to radiologists, and thus, new tools for reliable, reproducible, and high-volume quantitative assessments are warranted. In this context, radiomics, which is an emerging field of research involving the conversion of digital medical images into mineable data for clinical decision-making and outcome prediction, has been gaining ground in oncology. Recent development in artificial intelligence has promoted radiomics studies in various fields including breast cancer treatment and numerous studies have been conducted. However, radiomics has shown a translational gap in clinical practice, and many issues remain to be solved. In this review, we will outline the steps of radiomics workflow and investigate clinical application of radiomics focusing on breast MRI based on published literature, as well as current discussion about limitations and challenges in radiomics.


An approach to airway management in the acutely head-injured patient.
The rapid and safe establishment and maintenance of an adequate airway in patients with acute, severe head injuries is of central importance in the "ABC" approach to the trauma victim. It is also necessary before hyperventilation can be instituted as a means of controlling intracranial pressure. A method of establishing an airway in a manner that best protects the patient from unnecessary elevations in intracranial pressure with the least possible risk is presented. This method can be applied in virtually all emergency departments, from community hospitals to teaching centers, using materials and expertise currently available.


Arthroscopic Focal Subspinal Decompression and Management of Pincer-Type Femoroacetabular Impingement.
Femoroacetabular impingement syndrome is a common hip pathology significantly affecting not only the intra- and extra-articular structures but also the biomechanical function of the joint. Cam and pincer bony lesions have been extensively studied. However, during recent years, other types of extra-articular impingement between the pelvic and femoral bone have been investigated. When a prominent or morphologically abnormal anterior-inferior iliac spine (AIIS) impinges repetitively on the femoral side during motion, the subspinal acetabular region becomes prominent and extends toward the intra-articular part of the joint. This results in restriction of the range of motion of the hip and pain, especially with flexion. Therefore, during hip arthroscopy, it is necessary to evaluate the subspinal region (triangular area located at 1:30 to 2:30 o'clock using the acetabular clock face system). For the correction of the acetabular bone pathology to be complete, the surgeon should focus both on the pincer and subspinal impingement lesions. This article describes our preferred technique to successfully address subspinal and pincer acetabular impingement during hip arthroscopy. The pearls and pitfalls of this technique are discussed.


A novel sustainable approach for the extraction of value-added compounds from Hibiscus sabdariffa L. calyces by natural deep eutectic solvents.
Hibiscus sabdariffa L. is widely acknowledged as an important source of value-added compounds as natural pigments and bioactive compounds whose isolation is of great interest in food industry. Due to the incessant demand of green extraction procedures, NADESs have emerged in the last years as new green solvents alternative to the conventional organic ones. The feasibility of NADESs for the extraction of value-added compounds of H. sabdariffa has been assessed in this work for the first time. An extraction technique based on microwave assisted extraction (MAE) and the use of NADESs was proposed testing different deep eutectic solvents based on choline chloride (ChCl). Among them, oxalic acid based NADES exhibited a great selectivity for anthocyanins in particular as well as higher extraction yields of bioactive compounds was also observed, even greater than those observed by methanol. The effect of extraction variables such as liquid-solid ratio, temperature and water percentage were studied by Box-Behnken design and a response surface methodology. The statistical program pointed out the liquid-solid ratio of 1:30 mL mg-1, temperature of 75 °C and a water percentage of 55% as the conditions to maximize extraction within the experimental domain. Hence, NADES composed by oxalic acid and choline chloride resulted to be an effective green alternative tailor-made solvent to carry out selective extractions of value-added compounds from H. sabdariffa.


Tetanus immunization among healthcare professionals: cross-sectional study in Turkey.
Vaccine-preventable diseases can be effectively managed through timely vaccine booster doses. In this study, the tetanus vaccination status of healthcare professionals and their level of knowledge about tetanus vaccination were investigated. The data were obtained through a survey questionnaire from 336 healthcare professionals. The survey participants were recruited on a voluntary basis among the personnel working in a tertiary hospital between 1 July 2021 and 30 September 2021. The participants were asked about their tetanus vaccination status and general awareness about the tetanus vaccine. The survey participants included nurses (41.4%, n = 139), doctors (39.9%, n = 134) and support unit personnel (18.8%, n = 63). The support unit personnel had insufficient knowledge about military service period, pregnancy period, vaccination of women aged 15-49 years, and the necessity of booster tetanus vaccine every 10 years. Interestingly, the nurses had significantly inadequate knowledge of geriatric tetanus vaccination. Although the tetanus immunization program is widely implemented throughout the country, our study concluded that it is necessary to educate healthcare professionals on the importance of the tetanus vaccine.


Diagnostic accuracy of ganglion cell complex substructures in different stages of primary open-angle glaucoma.
To evaluate diagnostic accuracy of substructure of ganglion cell complex versus peripapillary nerve fiber layer (NFL) thickness using spectral domain optical coherence tomography (SD-OCT) in different stages of glaucoma. Thirty eyes were normal, 120 were glaucomatous. Glaucomatous eyes were classified into: early glaucoma (46), moderate glaucoma (48), and severe glaucoma (26). Perimetry and SD-OCT were done. Peripapillary NFL thickness, ganglion cell layer (GCL), macular NFL thickness, combined GCL and macular ganglion cell complex (GCC), were recorded. Area under receiver operating characteristic curves (AUCs) was used to verify performance of different OCT parameters. Peripapillary NFL, GCL, and GCC thickness values were significantly different in all stages of glaucoma. All comparisons were significantly different; normal versus early, early versus moderate and moderate versus severe. The best parameters that distinguished normal from early stage were: peripapillary NFL (AUC: 0.90), GCC (AUC: 0.75), early from moderate stage were: peripapillary NFL thickness (AUC: 0.85), GCL (0.81),GCC (0.81), moderate from severe stage were: GCC (AUC:0.95), macular NFL (AUC:0.91), GCL (AUC:0.89), and peripapillary NFL (AUC:0.88). Peripapllary NFL and GCC thinning showed paradoxical course. The most diagnosed parameter in early glaucoma was peripapillary NFL and in severe glaucoma was GCC. In severe glaucoma, macular NFL showed higher diagnostic power than GCL and peripapillary NFL. Ganglion cell complex mapping may provide good alternative to optic disc imaging in advanced glaucoma with poor fixation.


Healthcare utilization after mass trauma: a register-based study of consultations with primary care and mental health services in survivors of terrorism.
Knowledge on healthcare utilization after mass trauma is needed to strengthen the public health preparedness to such incidents. Using register-based data, this study had a unique opportunity to investigate how young survivors' use of primary care physicians (PCP) and mental health services (MHS) changed after a terrorist attack. We examined register-based data on PCP and MHS consultations among 255 survivors (52% male) of the 2011 Utøya youth camp attack in Norway 3 years before and after the attack, and their reason for encounter with the PCP according to the International Classification for Primary Care (ICPC- 2). The PCP and MHS consultation rates (CR) were higher in female than male survivors both acutely and at long-term. The mean yearly CRs increased from 2.25 to 4.41 for PCP and 1.77 to 13.59 for MHS the year before and after the attack in female survivors, and from 1.45 to 3.65 for PCP and 1.02 to 11.77 for MHS in male survivors. The third year post-attack CRs for PCP were 3.55 and 2.00; and CRs for MHS were 5.24 and 2.30 in female and male survivors, respectively. Among female survivors, 76% consulted PCP and 12% MHS the year preceding the attack; post-attack 93% consulted PCP and 73% MHS the first year; decreasing to 87 and 40% the third year. Among male survivors, 61% consulted PCP and 7% MHS the year preceding the attack; post-attack 86% consulted PCP and 61% MHS the first year, and 67 and 31% the third year. As for PCP consultations, there was a particular increase in psychological reasons for encounter following the attack. This study indicates that it is important to anticipate an increased healthcare utilization several years following mass trauma, particularly of MHS. Both PCP and MHS practitioners played important roles in providing healthcare for psychological problems in young survivors of terrorism in a country with universal and largely publicly financed healthcare and a gatekeeping system. The healthcare utilization could be different in countries with other health systems or psychosocial care responses to mass trauma.


Comparative Study of Peripheral Rim Fixation Using Jumbo Cup in Revisional Hip Arthroplasty.
It is challenging procedure to revise acetabular component in acetabulum with severe bone defect or deformity. The jumbo cup is good option for revisional arthroplasty in large bone defect. The purpose of this study is to compare the prognosis of revisional total hip arthroplasty using jumbo cup with peripheral rim fixation and no rim fixation. We included the patients who had performed acetabular revisional total hip arthroplasty from January 2002 to March 2015 in our institute. Total of 51 hips (51 patients) were included. The mean follow up period was 51 months (range, 12 to 154 months) and mean age was 60.7 years (range, 30 to 81 years). We divided into two groups (peripheral rim fixation group and no rim fixation group) by anteroposterior and lateral plain radiograph. We compared survival rate, hip center change and clinical outcomes between two groups. There were 37 patients in peripheral rim fixation group and 14 patients in no rim fixation group. There was one patient who had aseptic loosening necessary to re-revision in rim fixation group and 3 patients in no rim fixation group. And one patient had superficial infection in rim fixation group and one patient had periprosthetic fracture in no rim fixation group. Survival rate was higher in the peripheral rim fixation group (97.3%) than no rim fixation group (78.6%, P=0.028). Based on our findings, peripheral rim fixation might be recommended to improve short-term outcome after revision total hip arthroplasty using jumbo cup.


Wakefield excitation in multimode structures by a train of electron bunches.
We discuss wakefield excitation and propagation in dielectric structures, particularly concentrating on the case of multiple drive beam excitation in multimoded structures. We emphasize calculations of the energy loss of the drive beam train, the amplitude of the wakefield, and the relationship between power flow and stored energy in the dielectric wakefield device. We show that for a collinear multimode structure the amplitude of the wakefield generated by a bunch train is less than or equal to the wakefield generated by a single bunch of the same total charge. Furthermore, the transformer ratio R is shown to be always less than 2, even in the multiple drive beam case.


Dupuytren's contracture--the role of fasciotomy.
This paper summarises the results obtained in 95 patients treated by fasciotomy, defines the indications for this procedure and describes the operative technique. During a period of seven years a total of 95 patients with 137 fingers affected by Dupuytren's Contracture have been treated by fasciotomy. The minimum follow-up is two years. The oldest patient was 79 years and no patient younger that 50 years was accepted for this form of treatment.


Effect of monocular light exclusion on the Stiles-Crawford function.
Contrary to previously published studies, monocular light exclusion did not alter the shape of the Stiles-Crawford function in a substantial manner in four subjects who were patched in this laboratory for one full week. In order to rule out methodological differences, an experimenter from each of the two sets of experiments (current and prior) patched one eye for 1 week, then tested each other. For one subject, there was little effect of patching. For the other, patching had a measurable effect, but it was different from that originally reported. However, the much larger, symmetrical broadening of the Stiles-Crawford function reported in earlier studies was not replicated. A testable working hypothesis to explain the earlier results is discussed.


Regulation of phospholipid hydrolysis and second messenger formation by protein kinase C.
The binding of a variety of agonists to their receptors leads to the breakdown of membrane phospholipids and the formation of intracellular second messengers. Hydrolysis of inositol phospholipids by phospholipase C results in the formation of two second messengers, inositol-1,4,5-trisphosphate which mobilizes intracellular calcium and the neutral lipid diacylglycerol (DAG) which binds to and activates protein kinase C (PKC). PKC is actually a family of homologous serine/threonine protein kinases which play a central role in regulation of growth, differentiation and secretion reactions in a variety of cell types. In addition to these feedforward roles of PKC, it is thought to play an important feedback role, regulating early events in signal transduction. To explore these feedback functions we have examined the effect of PKC inhibitors on second messenger formation in thrombin-stimulated human platelets (a rapidly responding system) and the effect of PKC overexpression on second messenger formation and mitogenesis in rat fibroblasts (a system where sustained signaling occurs). Treatment of platelets with inhibitors of PKC potentiates DAG mass formation in response to thrombin while prior activation of PKC with phorbol esters blocks DAG mass formation, consistent with PKC playing a negative feedback role, inhibiting inositol phospholipid breakdown. DAG can also be formed by the sequential hydrolysis of phosphatidylcholine by phospholipase D and phosphatidic acid phosphohydrolase. This is a minor reaction in the rapidly responding platelet system, but may play a role in sustained signaling events. We have found that fibroblasts which overexpress the beta 1 isozyme of PKC display greatly enhanced DAG formation and phospholipase D activation in response to phorbol ester treatment. Upon stimulation of fibroblasts with thrombin, phospholipase D activation is also enhanced by PKC overexpression while formation of inositol phosphates is suppressed. These data suggest that PKC may act as a switch, terminating inositol phospholipid hydrolysis and activating the hydrolysis of phosphatidylcholine. Furthermore, we have observed a strong correlation between activation of phospholipase D and mitogenesis, suggesting an important role for this enzyme in long-term cellular responses to activation.


Controllable self-assembly of nanoparticles for specific delivery of multiple therapeutic molecules to cancer cells using RNA nanotechnology.
By utilizing RNA nanotechnology, we engineered both therapeutic siRNA and a receptor-binding RNA aptamer into individual pRNAs of phi29's motor. The RNA building block harboring siRNA or other therapeutic molecules was fabricated subsequently into a trimer through the interaction of engineered right and left interlocking RNA loops. The incubation of the protein-free nanoscale particles containing the receptor-binding aptamer or other ligands resulted in the binding and co-entry of the trivalent therapeutic particles into cells, subsequently modulating the apoptosis of cancer cells and leukemia model lymphocytes in cell culture and animal trials. The use of such antigenicity-free 20-40 nm particles holds promise for the repeated long-term treatment of chronic diseases.


Mice acquire flavor preferences during shipping.
Vigorous motion can cause rodents to develop flavor aversions and show other signs of malaise. We tested whether a flavor aversion could be induced by shipping mice from an animal breeder to a test site. Boxes of 12 male C57BL/6J mice were shipped approximately 950 km from Bar Harbor, ME to Philadelphia, PA by truck. For some boxes, the gel provided for hydration was flavored with almond and for others it was flavored with banana. After the journey, the mice were individually housed and allowed to recover for 5 days. They then received a choice between the two flavors of gel. Contrary to expectations, mice preferred the flavor they had previously ingested during shipping. Controls given flavored gel under similar conditions but while stationary did not show a preference. These results suggest that mice find shipping or its sequelae pleasurable. If mice are travel sick this must be inconsequential relative to other components of the shipping experience.


An unusual cause of massive non-surgical pneumoperitoneum: case report.
A case of pneumoperitoneum due to cocaine abuse is presented. Although most commonly associated with surgical disease, pneumoperitoneum may actually be a manifestation of non-surgical intrathoracic pathology. In this patient percutaneous diagnostic peritoneal lavage resulted in return of a large quantity of air and was negative for bleeding or contamination.


Continuous Regional Arterial Infusion of Protease Inhibitors for Treatment of Severe Acute Pancreatitis: Systematic Review and Meta-Analysis.
We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) to assess the benefit and risk of continuous regional arterial infusion (CRAI) of protease inhibitors (CRAIpis) in patients with severe acute pancreatitis (SAP) or acute necrotizing pancreatitis (ANP). The search was performed using the key words "pancreatitis" and "regional arterial infusion." All language studies involving adult cases of SAP or ANP, which assessed the impact of the CRAIpis, were included. Our analysis included 8 observational studies and 2 RCTs from 376 potentially relevant articles. With regard to the observational studies, the CRAIpi was significantly associated with decreased both mortality (odds ratio, 0.40; 95% confidential interval [CI], 0.25-0.64; P = 0.0001) and the need for urgent surgical intervention (odds ratio, 0.22; 95% CI, 0.12-0.3; P < 0.0001). In the RCTs, the application of CRAIpi tends to decrease the mortality but does not reach the significance (risk reduction, -0.12; 95% CI, -0.36-0.12; P = 0.33). The CRAIpi has the potential to reduce the mortality or the need for urgent surgical intervention in cases of SAP or ANP. Further, large multicenter trials are needed to refute or confirm our findings.


Interventional radiology strategies in the treatment of pseudomyxoma peritonei.
To describe percutaneous maneuvers to treat the unusual entity symptomatic pseudomyxoma peritonei (PMP). Four patients with PMP were treated by interventional radiology techniques that included large catheters (20-30 Fr) alone (n = 3), multiple catheters (n = 4), and dextran sulfate as a catalytic agent through smaller catheters (n = 1). The causes of the PMP were tumors in the ovary (2 patients), appendix (1 patient), and colon (1 patient). Each patient previously had undergone at least two operations to remove the PMP, and all patients had symptomatic recurrence. An in vitro analysis of catalytic agents also was performed. All four patients improved symptomatically. Follow-up CT scans demonstrated marked reduction of PMP material in all cases. One patient underwent another interventional radiology session 5 months after the first; the other three patients had no recurrence of symptoms. One patient had reversible hypotension 2 hr after the procedure. The amount of material removed varied from 3 to 6 L. These interventional radiology techniques were effective and safe for PMP and suggest options for this difficult medical and surgical problem.


Exploring the potential of common iceplant, seaside arrowgrass and sea fennel as edible halophytic plants.
The recent interest in diversification in food consumption and the current salinization and desertification processes of farmland have placed the focus on halophytic plants as new food, making necessary the characterization of their biochemical composition and the identification of possible bioactive compounds. In this work, three edible halophytic plants were characterized: common iceplant (Mesembryanthemum crystallinum), sea fennel (Crithmum maritimum), and seaside arrowgrass (Triglochin maritima). The plants studied were a good source of minerals. Sea fennel showed high contents of dietary fibre and calcium (8.5 ppm, wet weight), common iceplant had a high potassium content (6500 ppm, wet weight), while seaside arrowgrass presented high levels of iron (62 ppm, wet weight). The glucose content of the three species was below 30 mg/g per dried weight. The Sb, Pb, Cr, As, Cd, and Hg content was negligible. Polyunsaturated fatty acids, mainly α-linolenic and linoleic acid, prevailed in the three species analyzed. Hydroxycinnamic and hydroxybenzoic acids predominated in common iceplant and sea fennel. Glycosylated flavones, especially isoorientin, prevailed in seaside arrowgrass. These plants present a relevant nutritional profile for which their use as foods or ingredients should be promoted.


Effects of chronic antihypertensive treatment with ketanserin versus metoprolol on blood pressure and large arteries' compliance in humans: a cross-over double-blind study.
The antihypertensive efficacy of a serotonin-receptor antagonist, ketanserin, was compared with that of a well-established antihypertensive drug, metoprolol, and their cardiac and forearm hemodynamic effects were investigated using echocardiography and bidimensional pulsed Doppler flowmetry, respectively. Twenty hypertensive subjects completed a double-blind, cross-over, randomized study using ketanserin and metoprolol. Two 5-week courses with ketanserin or metoprolol were preceded by a placebo period; the total duration of the study was 15 weeks. Despite a comparable efficacy in reducing systolic and diastolic blood pressure (about 10% of the basal value), the two drugs showed quite different effects on forearm hemodynamics. Ketanserin increased forearm blood flow and induced a significant decrease in forearm vascular resistance (from 141 +/- 16 to 75 +/- 11 mm Hg/mL/sec, P less than .01). Furthermore, this treatment was able to improve brachial artery compliance (from 1.89 +/- .3 to 3.2 +/- .3 cm4/dyne 10(-7), P less than .01). On the contrary, metoprolol did not modify forearm hemodynamics. Both drugs did not significantly modify cardiac performance, as evaluated by left ventricle circumferential fiber shortening. Cardiac output was increased by ketanserin (from 5.9 +/- .3 to 6.6 +/- .5 L/min, P less than .05) and fell during treatment with metoprolol (from 5.9 +/- .4 to 4.9 +/- .3 L/min P less than .01). Thus, the two drugs reduce blood pressure through different hemodynamic mechanisms and the effects of ketanserin on systemic and peripheral circulation seem more favorable.


Pre-hospital plasma in haemorrhagic shock management: current opinion and meta-analysis of randomized trials.
Trauma-induced coagulopathy is one of the most difficult issues to manage in severely injured patients. The plasma efficacy in treating haemorrhagic-shocked patients is well known. The debated issue is the timing at which it should be administered. Few evidences exist regarding the effects on mortality consequent to the use of plasma alone given in pre-hospital setting. Recently, two randomized trials reported interesting and discordant results. The present paper aims to analyse data from those two randomized trials in order to obtain more univocal results. A systematic review with meta-analysis of randomized controlled trials (RCTs) of pre-hospital plasma vs. usual care in patients with haemorrhagic shock. Two high-quality RCTs have been included with 626 patients (295 in plasma and 331 in usual care arm). Twenty-four-hour mortality seems to be reduced in pre-hospital plasma group (RR = 0.69; 95% CI = 0.48-0.99). Pre-hospital plasma has no significant effect on 1-month mortality (RR = 0.86; 95% CI = 0.68-1.11) as on acute lung injury and on multi-organ failure rates (OR = 1.03; 95% CI = 0.71-1.50, and OR = 1.30; 95% CI = 0.92-1.86, respectively). Pre-hospital plasma infusion seems to reduce 24-h mortality in haemorrhagic shock patients. It does not seem to influence 1-month mortality, acute lung injury and multi-organ failure rates.Level of evidence: Level IStudy type: Systematic review with Meta-analysis.


Combinational study with network pharmacology, molecular docking and preliminary experiments on exploring common mechanisms underlying the effects of weijing decoction on various pulmonary diseases.
'Homotherapy for heteropathy' is a theory by which different diseases with similar pathogenesis can be treated with one Chinese formula. We aimed to explore the key components and core targets of Weijing decoction (WJD) in treating various lung diseases, namely, pneumonia, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), pulmonary fibrosis, pulmonary tuberculosis and non-small cell lung cancer (NSCLC), via network pharmacology, molecular docking and some experiments. This is the first study on the mechanism of WJD in treating various lung diseases by 'homotherapy for heteropathy'. This study is helpful for the transformation of TCM formula and development of new drugs. Active components and therapeutic targets of WJD were obtained via TCMSP and UniProt databases. Targets of the six pulmonary diseases were harvested from the GeneCards TTD, DisGeNet, UniProt and OMIM databases. Drug-disease intersection targets, corresponding Venn diagrams, herb-component-target networks and protein-protein interaction networks were established. Furthermore, GO biological function and KEGG enrichment analysis were completed. Moreover, the binding activity between main compounds and core targets was measured through molecular docking. Finally, the xenograft NSCLC mouse model was established. Immune responses were evaluated by flow cytometry and mRNA expression levels of critical targets were measured by real-time PCR. JUN, CASP3 and PTGS2 were the most critical targets in six pulmonary diseases. The active compounds beta-sitosterol, tricin and stigmasterol stably bound to many active sites on target proteins. WJD had extensive pharmacological regulation, involving pathways related to cancer, inflammation, infection, hypoxia, immunity and so on. Effects of WJD against various lung diseases involve lots of compounds, targets and pathways. These findings will facilitate further research as well as clinical application of WJD.


Pemphigus.
The term pemphigus refers to a group of autoimmune intraepidermal blistering diseases of the skin and mucous membranes. Several clinical variants of pemphigus are recognized. The major histologic feature of all variants is acantholysis, the disruption of normal cell-to-cell adhesion, which leads to intraepidermal blister formation. Most patients with pemphigus demonstrate IgG autoantibodies directed against an antigen located on the surface of keratinocytes. Although the stimulus for autoantibody production is unknown, several mechanisms have been proposed to explain the pathogenesis of acantholysis. One popular model proposes that pemphigus antibodies induce acantholysis through local stimulation of the plasminogen-plasmin system. Another model proposes that pemphigus antibodies fix complement and thereby alter cell membrane integrity to produce acantholysis. Prior to the availability of corticosteroids, pemphigus vulgaris was commonly fatal. Treatment with glucocorticosteroids has drastically improved the prognosis. Immunosuppressive agents and plasmapheresis have been used successfully in some patients with severe disease.


Determinants of early discontinuation of long-acting and reversible contraceptive methods among women within childbearing age attending health facilities in Ethiopia, 2019.
This study aimed to identify the determinants of early discontinuation of long-acting and reversible contraceptive methods among women within childbearing age in Ethiopia, 2019. The institutional-based case-control study design was implemented from June to August 2019. Eligible study participants were sampled using systematic random sampling technique. Data were collected using structured and pre-tested questionnaire and entered into Epi Info and exported to SPSS version 20 for further analysis. All variables with a p value of <0.05 at odds ratio of 95% confidence interval in multivariable logistic regression analysis were considered as determinants of early discontinuation of long-acting and reversible contraceptive methods. A total of 825 study participants (206 cases and 619 controls) were included in the study. Decision-making on the use of contraception (adjusted odds ratio: 4.8, 95% confidence interval: 1.4-16.8 and adjusted odds ratio: 5.6, 95% confidence interval: 1.7-18.8), the women who got counseled about side effects of contraceptive methods being 84% less likely to discontinue long-acting and reversible contraceptive methods compared to the women of their counterpart (adjusted odds ratio: 0.16, 95% confidence interval: 0.15-0.4), having two or more children (adjusted odds ratio: 10, 95% confidence interval: 3.7-28), and desire to be pregnant (adjusted odds ratio = 0.15 95% confidence interval: 0.06-0.4) were determinants of early discontinuation of long-acting and reversible contraceptive methods. According to the findings of this study, decision-maker on utilization of contraceptive methods, being counseled on side effects of contraception, number of children, and desire of woman to be pregnant were found to be determinants of discontinuation of long-acting and reversible contraceptive methods. Health care providers should strengthen providing pre-insertion counseling in accordance with the national guideline for family planning services, with an emphasis on potential contraceptive side effects and consideration of counseling on decision-making.


Total parenteral nutrition associated cholestasis: a predisposing factor for sepsis in surgical neonates?
Of 496 neonates and infants less than 1 year of age admitted to the paediatric surgical intensive care unit (PSICU) over a 5 year period (1983-1987), 94 required total parenteral nutrition (TPN) for more than 14 consecutive days, generally due to congenital anomalies of the digestive tract. Cholestasis occurred in 15 of them and 12 of these patients developed sepsis. In contrast, of the 79 patients on TPN that remained free from cholestasis, only 23 developed sepsis. The mortality rate for the TPNAC-group was substantially higher than for the group without TPNAC. It is suggested that development of TPNAC might lead to impairment of non-specific cellular immunity in neonates.


Medial Prefrontal Aberrations in Major Depressive Disorder Revealed by Cytoarchitectonically Informed Voxel-Based Morphometry.
The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder. The contribution of the medial (socio-affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The authors performed morphometric comparison of the microstructurally informed subdivisions of human frontal pole between depressed patients and comparison subjects using both uni- and multivariate statistics. Multisite voxel- and region-based morphometric MRI analysis was conducted in 73 depressed patients and 73 matched comparison subjects without psychiatric history. Frontal pole volume was first compared between depressed patients and comparison subjects by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines. Subdivision-wise morphometric analysis found a significantly smaller medial frontal pole in depressed patients, with a negative correlation of disease severity and duration. Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients. Across disparate methods, subregion specificity in the left medial frontal pole volume in depressed patients was demonstrated. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology, such as the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression.


HLA class I genes integrated into murine cells are inducible by interferon.
In human cells treated with interferon, there is an increase in the amount of HLA-A, B, C mRNA and, to a lower extent, membrane-bound antigen. However, the mechanism of this mRNA enhancement is still unknown. Using mouse L cells transfected with a unique class I HLA gene, we were able to show that both the related HLA mRNA and protein are increased after murine but not human interferon treatment. Moreover, the discrepancy between interferon-directed HLA mRNA and protein enhancement is also observed. The mouse transfected cells allowed us to study more precisely the origin of this discrepancy.


Enhanced carboxyl methylation of membrane-associated hemoglobin in human erythrocytes.
The alpha- and beta-chains of hemoglobin (Hb) are methylated in intact erythrocytes and in cellular extracts by a protein D-aspartate methyltransferase (EC 184.108.40.206) specific for D-aspartyl and L-isoaspartyl residues. During an 18-h incubation of intact erythrocytes with L-[methyl-3H]methionine, the subfraction of Hb molecules associated with the membrane becomes progressively enriched with methyl esters, reaching a specific activity 10-fold that of cytosolic Hb. The enhanced methylation of membrane Hb in intact cells appears not to result from its methylation at sites with inherently greater stability, since salt-extracted membrane Hb 3H-methyl esters and cytosolic Hb 3H-methyl esters are hydrolyzed at similar rates at pH 8.4 in vitro. Oxidative treatment of column-purified Hb with acetylphenylhydrazine produces an immediate 4-fold increase in its specific methyl-accepting activity coincident with the production of hemichrome forms known to possess a higher affinity for membrane binding sites. Together, the results suggest that the methyltransferase preferentially recognizes partially denatured Hb molecules which possess a higher affinity for membrane binding sites, similar to Hb forms observed in senescent erythrocytes.


Dimensionality, internal consistency and interrater reliability of clinical performance ratings.
A total of 6444 ratings of the financial performance of 424 third- and fourth-year medical students were made by house officers and attending teachers during 12 separate internal medicine rotations. Ratings were based on 13 behaviourally anchored rating scales. One rating was randomly selected per student per evaluator type (house officer and attending teacher) during each of the 12 rotation periods. Ratings were factor analysed separately within each rotation period. Two factors emerged consistently, and congruence coefficients across the 12 occasions were high (0.88 or greater). The factors were labelled 'problem-solving (10 items) and 'interpersonal skills' (three items) on the basis of their content. Internal consistency coefficients of the indices constructed from items in the two factors and the total of the 13 items were high (0.9 or greater) and did not differ substantially when computed separately on the ratings from house officers and attending teachers. Interrater reliabilities on the individual items ranged from 0.14 to 0.33.


Anesthesia for magnetic resonance imaging in children: a low incidence of protracted post-procedure vomiting.
To determine the incidence and severity of vomiting in pediatric patients who have had inhalation anesthesia for magnetic resonance imaging (MRI). A retrospective study of consecutive pediatric patients who had anesthesia for MRI. A large university hospital with an integrated clinic facility. 234 children who required an MRI under general anesthesia over a 30 month period (July 1989 to February 1992). The duration of inhalation anesthesia was 105 +/- 33 minutes. Following anesthesia, the time to oral intake was 92 +/- 69 minutes. Eighteen patients (9%) experienced one or more episodes or emesis. In 14 of the 18 patients, vomiting occurred once and did not delay the intake of oral fluids or the discharge time from clinic when compared with the rest of the patients. Only one patient had frequent vomiting (more than three episodes), and all vomiting resolved spontaneously without anti-emetic therapy in less than eight hours following anesthesia. Protracted post-procedure vomiting is an infrequent complication of inhalation anesthesia for MRI. Inhalation anesthesia may be a less important cause of postoperative vomiting than factors such as the type of operative procedure, use of opioids, or presence of postoperative pain.


Regulation of multidrug resistance protein 2 (MRP2, ABCC2) expression by statins: involvement of SREBP-mediated gene regulation.
Multidrug resistance protein 2 (MRP2, ABCC2) is localized to the apical membrane of hepatocytes and played an important role in the biliary excretion of a broad range of endogenous and xenobiotic compounds and drugs, such as pravastatin. However, the effects of statins on MRP2 in the liver and the precise mechanisms of their actions have been obscure. The goal of this study was to determine the regulatory molecular mechanism for statin-induced MRP2 expression in hepatocytes. In vitro and in vivo studies suggested that pitavastatin increased MRP2 expression. Pitavastatin promoted liver X receptor (LXR) α/β translocation from the cytosol to nuclei, resulting in LXR activation. Deletion and mutational analysis suggested that the potential sterol regulatory element (SRE) played a major role in the observed modulation of MRP2 expression by pitavastatin. Furthermore pitavastatin increased the protein-DNA complex, and when SRE was mutated, stimulation of the protein-DNA complex by pitavastatin was decreased. It was demonstrated that pitavastatin upregulated MRP2 expression by an SREBP regulatory pathway in hepatocytes and that the actions of statins may lead to improve the biliary excretion of MRP2 substrates.


Isolation of plasma membrane complexes from Xenopus oocytes.
A method for the isolation of plasma membrane fractions from Xenopus oocytes has been developed, and the membranes have been characterized biochemically and morphologically. Plasma membrane complexes prepared by this procedure consisted of large sheets of the membrane, with associated vitelline envelope (a nonmembranous meshwork of fibers) and cortical (secretory) granules still attached. The morphology of cell surface microvilli and coated pits was well preserved. Cortical granules were removed by gentle homogenization in a low ionic strength medium, and integral and peripheral membrane proteins were then separated from vitelline envelopes by detergent extraction and phase separation in Triton-X-114. Biochemical characterization of the plasma membrane fractions indicated substantial levels of 5'-nucleotidase and alkaline phosphodiesterase activity associated with the oocyte cell surface, with 44-66% recovery of these markers in the final membrane preparations. Lectin blotting and lectin affinity chromatography with Concanavalin A and wheat germ agglutinin were used to characterize the major glycoprotein species associated with the plasma membrane complexes. Plasma membrane fractions prepared by this procedure should be very useful in both biochemical and morphological studies of membrane protein sorting in the Xenopus oocyte system.


[Klebsiellae isolated from patients and healthy subjects. III. Biochemical types of klebsiellae].
By the difference in fermentation of glucose, lactose, saccharose, inosite, adonite, behaviour in IMViC tests, relation to urine and hydrogen sulfide formation there were revealed 10 biochemical types among 120 strains of klebsiellae. Klebsiellae of biotypes 1 and 2 were the most frequently isolated from the patients; biotypes 3--10 were less frequent. Klebsiella of biotypes 1 and 2 were revealed in healthy persons; biotypes 3--10 were never found. Biochemical reactions on whose basis klebsiellae were referred to the definite biochemical type proved to be stable.


Nanofibers-based nanoweb promise superhydrophobic polyaniline: from star-shaped to leaf-shaped structures.
Star-shaped and leaf-shaped polyaniline (PANI) hierarchical structures with interlaced nanofibers on the surface were successfully prepared by chemical polymerization of aniline in the presence of lithium triflate (LT). Chemical structure and composition of the star-like PANI obtained were characterized by FTIR and UV-vis spectra. PANI 2D architectures can be tailored from star-shaped to leaf-shaped structures by change the concentration of LT. The synthesized star-like and leaf-like polyaniline show good superhydrophobicity with water contact angles of both above 150° due to the combination of the rough nanoweb structure and the low surface tension of fluorinated chain of dopant. This method is a facile and applicable strategy for a large-scale fabrication of 2D PANI micro/nanostructures. Many potential applications such as self-cleaning and antifouling coating can be expected based on the superhydrophobic PANI micro/nanostructures.


Morphine induced changes in ethanol-and water-intake are attenuated by the 5-HT3/4 antagonist tropisetron (ICS 205-930).
The opiate agonist morphine has been shown to increase ethanol intake and mesolimbic dopamine (DA) levels. Conversely, the 5-HT3/4 antagonist tropisetron has been shown to decrease ethanol intake and morphine-induced increases in mesolimbic DA levels. This study was designed to test the effects of acutely administered tropisetron on morphine-induced changes in ethanol (6% v/v) and water intake in a two-bottle test procedure. Ten water restricted male rats were injected with combinations of morphine (0.0, 0.56, 1.0, 1.5, 10.0, and 17.0 mg/kg, SC) and tropisetron (0.0, 1.0, 10.0, and 17.0 mg/kg, SC) prior to test sessions. Morphine (1.0 and 1.5 mg/kg) significantly increased absolute (g/kg) and relative ethanol intake (ethanol/total fluid). Tropisetron alone did not affect ethanol or water intake. When tropisetron (10.0 and 17.0 mg/kg) was administered in combination with morphine (1.5 mg/kg), the increase in ethanol intake induced by morphine was attenuated. Tropisetron (1.0 mg/kg) reversed a decrease in ethanol intake induced by morphine (17.0 mg/kg). The two highest doses of tropisetron partially attenuated a significant decrease in water intake produced by morphine (17.0 mg/kg). These data suggest that opiate and 5-HT3 mechanisms could interact in the regulation of ethanol intake. However, the doses of tropisetron tested were high and, therefore, the potential involvement of 5-HT4 receptors or other neurotransmitter systems in regulating ethanol intake is discussed.


Production of a biologically active variant form of recombinant human secretin.
A biologically active variant form of recombinant human secretin was produced using a gene fusion system designed to facilitate the purification of the protein. The fusion protein was recovered from the culture medium of Escherichia coli by IgG affinity chromatography, and recombinant secretin was released by cyanogen bromide treatment. A novel approach involving addition of a C-terminal Gly-Lys-Arg extension, was used to overcome the lack of amidation of recombinant proteins in Escherichia coli. The biological activity of the recombinant variant of secretin was at least 80% of the porcine secretin standard.


Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis.
Lymphocytic interstitial pneumonitis (LIP) and nonspecific interstitial pneumonitis (NIP) are pulmonary complications of human immunodeficiency virus (HIV) infection that occur in the absence of a detectable opportunistic infection or neoplasm. We reviewed lung biopsy specimens from 50 adult HIV-infected patients, of whom four had LIP and 46 had NIP. The majority (47 of 50) of specimens from patients with NIP showed mild chronic interstitial pneumonitis (CIP/NIP), with three showing features of diffuse alveolar damage, organizing phase. In contrast to CIP/NIP, the five specimens from four patients with LIP demonstrated more extensive lymphocytic interstitial infiltrates that extended into the alveolar septal interstitium. The majority of the interstitial lymphocytes in both NIP and LIP were of T-cell origin and stained for UCHL-1. The etiologies of NIP and LIP remain unknown. Since the common opportunistic infections were excluded by routine methods, we sought, with special techniques, to investigate whether HIV, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) could be identified in lung biopsy specimens from these patients. By in situ hybridization, we found one LIP specimen with expression of large amounts of HIV RNA primarily within macrophages in germinal centers; in the remaining specimens, occasional cells expressing HIV RNA were found (two LIP and four NIP). Neither CMV nor EBV was found by in situ hybridization in seven specimens; in these same specimens EBV was detected using the polymerase chain reaction in only one case of NIP, similar to results in control specimens. These results, together with the knowledge that lymphocytic pulmonary lesions may be caused by lentiviruses in humans and animals, suggest that HIV plays a significant role in the pathogenesis of both NIP and LIP in adult HIV-infected patients; in contrast, our data do not demonstrate a direct role for either EBV or CMV.


Influence of COVID-19 lockdown on river water quality and assessment of environmental health in an industrialized belt of southern Western Ghats, India.
The COVID-19 pandemic and sudden lockdown have severely hampered the country's economic growth and socio-cultural activities while imparting a positive effect on the overall fitness of the environment especially air and water resources. Increased urbanization and rapid industrialization have led to rising pollution and deterioration of rivers and associated sectors such as agriculture, domestic and commercial needs. However, various available studies in different parts of the country indicate that the COVID-19 pandemic has changed the entire ecosystem. But it is noted that studies are lacking in the southern Western Ghats region of India. Therefore, the present study attempts to investigate how the continuous lockdowns affect the River Water Quality (RWQ) during lockdown (October 2020) and post-lockdown (January 2021) periods in the lower catchments (Eloor-Edayar industrialized belt) of Periyar river, Kerala state, South India. A total of thirty samples (15 samples each) were analyzed based on drinking water quality, irrigational suitability, and multivariate statistical methods to evaluate the physical and chemical status of RWQ. The results of the Water Quality Index (WQI) for assessing the drinking water suitability showed a total of 93% of samples in the excellent and good category during the lockdown, while only 47% of samples were found fit for drinking during the post-lockdown period. Irrigational suitability indices like Mg hazard, KR, PI, SAR, and Wilcox diagram revealed lockdown period samples as more suitable for irrigational activities compared to post-lockdown samples with site-specific changes. Spearman rank correlation analysis indicated EC and TDS with a strong positive correlation to Ca2+, Mg2+, Na+, K+, TH, SO42-, and Cl- during both periods as well as strong positive correlations within the alkaline earth elements (Ca2+ and Mg 2+) and alkalis (Na+ and K+). Three significant components were extracted from principal component analysis (PCA), explaining 88.89% and 96.03% of the total variance for lockdown and post-lockdown periods, respectively. Variables like DO, BOD, Ca2+, NO3-, and Cl- remained in the same component loading during both periods elucidating their natural origin in the basin. The results of health risk assessment based on US EPA represented hazard quotient and hazard index values below the acceptable limit signifying no potential noncarcinogenic risk via oral exposure except As, suggesting children as more vulnerable to the negative effects than adults. Furthermore, this study also shows rejuvenation of river health during lockdown offers ample scope to policymakers, administrators and environmentalists for deriving appropriate plans for the restoration of river health from anthropogenic stress.


Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers.
Squamous cell carcinoma of the vulva is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus. We used comparative genomic hybridisation to document non-random chromosomal gains and losses within human papillomavirus positive and negative vulvar cancers. Gain of 3q was significantly more common in human papillomavirus-positive cancers compared to human papillomavirus-negative cancers. The smallest area of gain was 3q22-25, a chromosome region which is frequently gained in other human papillomavirus-related cancers. Chromosome 8q was more commonly gained in human papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21 was the smallest region of gain, which has been identified in other, non-human papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both categories of vulvar cancer. This study has demonstrated chromosome locations important in the development of vulvar squamous cell carcinoma. Additionally, taken together with previous studies of human papillomavirus-positive cancers of other anogenital sites, the data indicate that one or more oncogenes important in the development and progression of human papillomavirus-induced carcinomas are located on 3q. The different genetic changes seen in human papillomavirus-positive and negative vulvar squamous cell carcinomas support the clinicopathological data indicating that these are different cancer types.


Epididymal white adipose tissue after cold stress in rats. I. Nonmitochondrial changes.
Epididymal adipose tissue in the rat is generally considered to be "pure" white adipose tissue (WAT) with a characteristic structure and function. Previous studies in cats have, however, indicated that adipose tissue with the morphological appearance of WAT could be converted into a tissue with the morphological appearance of brown adipose tissue (BAT) by intermittent cold stress. The present electron microscopic and morphometric study describes the effect of intermittent cold stress on the epididymal WAT of young rats. The tissue volume decreased markedly as did the lipid content. The mitochondrial volume increased dramatically. The extracellular matrix was vastly reduced as was the thickness of the plasma membrane, and the number of gap junctions between adipocytes increased markedly. Indications of neoinnervation and neovascularization were observed. A great abundance of preadipocytes indicated proliferative activity of the endothelium. The low amount of lipid droplets and a relative abundance of smooth and rough endoplasmic reticulum. Golgi apparatus, and lysosomes in the epididymal WAT of cold-stressed rats gave the cells the morphological appearance of young adipocytes or preadipocytes whereas the hypertrophic and hyperplastic mitochondria, the relative paucity of ribosomes on lipid droplet membranes, and the increased innervation and vascularization gave the cells the morphological characteristics of brown adipose tissue.


The prediction of preschool children's weight from family environment factors: gender-linked differences.
The main objective of this study was to test an explanatory model predicting preschool girls' and boys' body weight from certain child variables (food intake, sedentary behaviors, and eating habits), as well as family variables (interaction during mealtime and level of family financial resources allocated to meeting children's eating needs). A randomized stratified subsample of parents was selected from a larger study (Quebec Longitudinal Study of Child Development, QLSCD-1998-2002), with a breakdown of 581 girls and 611 boys of 4 years of age. Children's skin fold ratio, weight, height, and Body Mass Index (BMI) were recorded. Questionnaires were administered to parents (usually the mother). Using structural equation modeling (SEM) separately for girls and boys, the family environment model of healthy weight development was tested. Results yielded a good fit of the model for both genders. For boys, significant predictors of body weight in the model were family food insecurity and conflicts during mealtime. Healthy eating was predicted by food insecurity, mealtime conflicts, and sedentary behaviors. Mealtime conflicts predicted sedentary behaviors. For girls, none of the variables predicted body weight, however food insecurity predicted less healthy eating. These results outline the importance of prevention and intervention within families with young children.


Florid reactive lymphoid hyperplasia of terminal ileum.
Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn's disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn's disease. In florid lymphoid hyperplasia limited resection may be curative.


7, 8-Dihydroxy-4-methylcoumarin reverses depression model-induced depression-like behaviors and alteration of dendritic spines in the mood circuits.
Major depressive disorder (MDD) is a common mental disorder characterized by a persistent feeling of sadness, slow thought, impaired focus and loss of interest but the underlying mechanisms are largely unknown. Dendritic spines play an important role in the formation and maintenance of emotional circuits in the brain. Abnormalities in this process can lead to psychiatric diseases. 7,8-Dihydroxy-4-methylcoumarin (Dhmc), a precursor in the synthesis of derivatives of 4-methyl coumarin, plays an important role in protecting the nervous system from developing diseases and its most distinctive feature is safety. The aim of this study was to investigate whether Dhmc alleviates chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and reverses CUMS-induced alterations in dendritic spines of principal neurons in brain areas of the emotional circuits including the hippocampus, medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and basolateral amygdala (BLA) in male rats. Our results showed that CUMS-induced depression-like behaviors were accompanied by a decrease in spine density in pyramidal neurons of both the hippocampal CA3 area and the mPFC, and an increase in spine density in both the neurons of BLA and the medium spiny neurons (MSNs) of the NAc, as well as a decrease in the levels of the AMPA receptor subunit GluA1 and Kalirin-7 in the hippocampus compared with the control group. Intraperitoneal injection (i.p.) of Dhmc to the CUMS-exposed rats ameliorated CUMS-induced depression-like behaviors and reversed CUMS-mediated alterations in spine density and the levels of both GluA1 and Kalirin-7. Our results show an important role of Dhmc in reversing CUMS-induced depression-like behaviors and CUMS-mediated alterations in spine density.


Henipavirus-induced neuropathogenesis in mice.
Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses that can cause fatal encephalitis in humans. Many animal models have been used to study henipavirus pathogenesis. In the mouse, HeV infection has previously shown that intranasal challenge can lead to neurological infection, however mice similarly challenged with NiV show no evidence of virus infecting the brain. We generated recombinant HeV (rHeV) and NiV (rNiV) where selected proteins were switched to examine their role in neuroinvasion in the mouse. These viruses displayed similar growth kinetics when compared to wildtype in vitro. In the mouse, infection outcomes with recombinant virus did not differ to infection outcomes of wildtype viruses. Virus was detected in the brain of 5/30 rHeV-challenged mice, but not rNiV-challenged mice. To confirm the permissiveness of mouse neurons to these viruses, primary mouse neurons were successfully infected in vitro, suggesting that other pathobiological factors contribute to the differences in disease outcomes in mice.


Assessing microleakage of class V resin composite restorations after Er:YAG laser and bur preparation.
This study aimed to evaluate the extent of microleakage in cavities prepared with bur and Er:YAG laser, hybridized with different bonding systems. Sixty bovine teeth were randomly divided into six groups (n = 10): (G1) Diamond bur + Single Bond; (G2) Diamond bur + AdheSE; (G3) Diamond bur + Clearfil SE Bond; (G4) Er:YAG (250 mJ, 4 Hz, 80.6 J/cm(2)) + Single Bond; (G5)Er:YAG + AdheSE, and (G6) Er:YAG + Clearfil. Cavities were restored with a micro-hybrid composite resin. After thermocycling, the specimens were stained with 2% methylene blue solution and sectioned in the mesiodistal direction. Dye penetration was scored based upon the extent of the dye using a light stereoscope. The Kruskal-Wallis and Mann-Whitney test revealed no statistically significant differences between the method of preparation (diamond bur and laser). However, statistical differences were found between the adhesives tested. Based on the results of this study, Er:YAG laser confirmed to be as effective as the conventional methods for preparing adhesive restorations.


Understanding Age-Related Longitudinal Dynamics in Abundance and Diversity of Dominant Culturable Gut Lactic Acid Bacteria in Pastured Goats.
Understanding gut lactic acid bacteria (LAB) in healthy hosts is an important first step in selecting potential probiotic species. To understand the dynamics of LAB in healthy goats, a cohort of thirty-seven healthy new-born goat kids was studied over a ten-month period. Total LAB was quantified using SYBR green qPCR. Seven hundred LAB isolates were characterized using microscopy, M13 RAPD genotyping and 16S rDNA sequencing. The highest and lowest LAB counts were detected at one week and ten months of age, respectively. Diverse LAB species were detected, whose identity and prevalence varied with age. The main isolates belonged to Limosilactobacillus reuteri, Limosilactibacillus fermentum, Lactobacillus johnsonni, Ligilactobacillus murinus, Ligilactobacillus salivarius, Limosilactobacillus mucosae, Lactiplantibacillus plantarum, Ligilactobacillus agilis, Lactobacillus acidophilus/amyolovolus, Pediococcus spp. and Enterococcus spp. Uniquely, L. reuteri and Pediococcus spp. were most common in pre- and peri-weaned goats, while Lactobacillus mucosae and Enterococcus spp. were predominant in goats one month and older. Based on RAPD genotyping, L. reuteri had the highest genotypic diversity, with age being a factor on the genotypes detected. This data may be relevant in the selection of age-specific probiotics for goats. The findings may also have broader implications by highlighting age as a factor for consideration in probiotic bacteria selection in other animal hosts.


Postoperative complication from hemostatic clips.
Hemostatic clips were found in a patient's bladder four months after radical retropubic prostatectomy. A calculus, which had formed on one clip, caused acute urinary retention. Inadvertent enclosure of the hemoclips within the bladder intraoperatively and early intraurethral migration of the hemoclips are possible causes of this complication. Although this problem is rarely reported, hemoclips should be used sparingly, if at all, around the vesicourethral anastomosis.


Pulmonary histological appearances in fatal paraquat poisoning.
The paper describes the histological appearances in the lungs from 11 fatal cases of paraquat poisoning. The study originated as an attempt to define the sequential changes in the condition and, from them, to assess the mode of action of the herbicide in the human. The main features of the "paraquat lung" include haemorrhage, extrusion of macrophages, oedema, "honeycombing", fibrosis and, rarely, epithelial hyperplasia. The indications are that the changes are progressive once a threshold tissue concentration has been reached. The appearances are compared to those in poisoning by hyperbaric oxygen and it is hypothesized that the toxic action of paraquat is to sensitize the lungs to oxygen at atmospheric pressure.


Characterization of influenza virus PB1 protein binding to viral RNA: two separate regions of the protein contribute to the interaction domain.
The interaction of the PB1 subunit of the influenza virus polymerase with the viral RNA (vRNA) template has been studied in vitro. The experimental approach included the in vitro binding of labeled model vRNA to PB1 protein immobilized as an immunoprecipitate, as well as Northwestern analyses. The binding to model vRNA was specific, and an apparent Kd of about 2 x 10(-8) M was determined. Although interaction with the isolated 3' arm of the panhandle was detectable, interaction with the 5' arm was prominent and the binding was optimal with a panhandle analog structure (5'+3' probe). When presented with a panhandle analog mixed probe, PB1 was able to retain the 3' arm as efficiently as the 5' arm. The sequences of the PB1 protein involved in vRNA binding were identified by in vitro interaction tests with PB1 deletion mutants. Two separate regions of the PB1 protein sequence proved positive for binding: the N-terminal 83 amino acids and the C-proximal sequences located downstream of position 493. All mutants able to interact with model vRNA were capable of binding the 5' arm more efficiently than the 3' arm of the panhandle. Taken together, these results suggest that two separate regions of the PB1 protein constitute a vRNA binding site that interacts preferentially with the 5' arm of the panhandle structure.


A novel weight-reducing operation: lateral subtotal gastrectomy with silastic ring plus small bowel reduction with omentectomy.
"The ideal bariatric operation should preserve normal gastroduodenal continuity, reduce food intake, and allow the addition of intestinal short-circuiting that would stimulate GLP-1 secretion" (Mason, Surg Obes Rel Dis, 1:123-125, 2005). 246 obese patients underwent a subtotal lateral gastric resection with silastic gastric ring placement, plus a moderate mid-small-bowel resection with omentectomy. This configuration preserves the pylorus, duodenum, 50-200 cm of jejunum, and 200-300 cm of ileum. The residual gastric pouch is 5-10 times larger than that in a standard Roux-en-Y gastric bypass (RYGB), and the length of small bowel in digestive continuity is 4-8 times greater than that in current diversionary malabsorptive procedures. Weight loss and amelioration of comorbidities were similar to results following conventional RYGB. An average of 36% total body weight loss, with BMI decrease of 17 kg/m(2), was observed at 1.5 years and was largely maintained at 3 years, without eating problems or evidence of malabsorption. The rate of mortality was 0.8%, major morbidity 7.7%, and minor morbidity 4.1%-all of which are comparable to RYGB. This procedure, which is technically less demanding than RYGB, preserves all or part of every segment of the gastrointestinal tract, including absorptive sites for iron and trace minerals. Despite substantially less gastric restriction than in RYGB, and less compromise of absorptive bowel than in biliopancreatic diversion, weight loss profiles are similar to those observed after these conventional bariatric operations. Favorable changes in gut hormones, including augmentation of ileal-brake peptides and reduction of ghrelin, may play a dominant role in affecting major, long-lasting weight loss.


Kinetics of odorant compounds in wine brandies aged in different systems.
The odorants compounds of aged wine brandies comprise compounds deriving from the wood, from the distillate and from the reactions that occur inside the barrel. The aim of this work was to study the kinetics of the odorant compounds of a wine brandy during two years of ageing in two ageing systems. The odorant compounds in the analysed brandies changed significantly over the time, but with different evolution patterns. The wood related compounds increased over time, with the highest increase in the first months of ageing. The kinetics of cis, trans-β-methyl-γ-octalactone, acetovanillone and of seven volatile phenols are established for the first time in brandies. Moreover, a significant effect of the ageing system was found on the kinetics of the wood related compounds. These results pointed out the interest of these compounds as a tool to discriminate different ageing technologies.


A 69-year-old woman with persistent iron deficiency anemia.
In women, iron deficiency anemia-a result of chronic iron loss-is most common during the reproductive years because of physiologic demands such as menstrual blood losses and pregnancy. In other cases, iron deficiency anemia is generally attributed to occult gastrointestinal bleeding. Common causes of chronic gastrointestinal blood loss include erosive esophagitis, gastric and duodenal ulcers, vascular ectasias, colon adenomas, and cancers. Bleeding from the small intestine at sites beyond the duodenal bulb is uncommon. The lesions of the small intestine are responsible for approximately 4% of gastrointestinal bleeding [7]. In this report we describe a case of persistent iron deficiency anemia due to carcinoid tumor of the small intestine.


Impact of preoperative hemoglobin and CRP levels on cancer-specific survival in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: results of a single-center study.
Different blood parameters have shown to be associated with patient's oncological outcome. There is only limited knowledge about the prognostic relevance of routine blood parameters in patients undergoing radical cystectomy for transitional cell carcinoma (TCC). Therefore, we retrospectively analyzed the influence of preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels on overall survival (OS) and cancer-specific survival (CSS). Preoperative CRP and Hb levels were available in 664 patients who underwent RC due to TCC from 2004 to 2013 at our institution. More men than women (77 vs. 23 %) underwent surgery with a median age of 70 years (35-97). Median follow-up time was 24 months (max. 108). Outcome was analyzed using Kaplan-Meier method, log-rank test, and Cox regression models. Median CRP level was 0.5 mg/dl (0.1-28.3), and median Hb level was 13.4 g/dl (6.7-17.9). Patients with CRP value above the median died significantly earlier due to their disease than those with CRP below the median (median CSS 19 vs. 70 months; p < 0.001). Patients with preoperative Hb level below the median had significantly worse outcome than those with Hb level above the median (median CSS 25 vs. 78 months; p < 0.001). In multivariate analysis, CRP and Hb levels were independent prognostic parameters regarding CSS/OS (CRP p = 0.016/p = 0.004; Hb p = 0.006/p = 0.004, respectively). In our single-center study, preoperative CRP and Hb levels were found to be independent prognostic factors, indicating impaired outcome in patients undergoing RC for TCC. These findings could be used for individual risk stratification and optimization of therapeutic strategies.


Exploring the potential impact of rotavirus vaccination on work absenteeism among female administrative personnel of the City of Antwerp through a retrospective database analysis.
Rotavirus vaccination has been reimbursed in Belgium since November 2006 with a high uptake (>85%). Economic analyses of the vaccine have been reported, including estimates of indirect cost gain related to the reduction in work absenteeism. The objective of this study was to evaluate the latter parameter using real-life data. A simple model estimated the reduction in absent workdays per working mother with a firstborn baby after the introduction of the rotavirus vaccine. Next, data on work absences were retrospectively analysed (from 2003 to 2012) using a database of administrative employees (n=11,600 working women per year) in the City of Antwerp. Observed reductions in absenteeism after the introduction of the vaccine were compared with the results from the model. These reductions would most likely be observed during the epidemic periods of rotavirus (from January to the end of May) for short-duration absences of ≤ 5 days. We compared data from outside epidemic periods (from June to December), expecting no changes over time prevaccine and postvaccine introduction, as well as with a control group of women aged 30-35 years with no first child. Model estimates were 0.73 working days gained per working mother. In the database of the City of Antwerp, we identified a gain of 0.88 working days during the epidemic period, and an accumulated gain of 2.24 days over a 3-year follow-up period. In the control group, no decrease in absenteeism was measured. Giving vaccine access to working mothers resulted in an estimated accumulated net cost gain of €187 per mother. Reduction in absenteeism among working mothers was observed during periods of the epidemic after the introduction of the rotavirus vaccine in Belgium. This reduction is in line with estimates of indirect cost gains used in economic evaluations of the rotavirus vaccine. HO-12-12768.


Imaging of inflamed carotid artery atherosclerotic plaques with the use of 99mTc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients.
Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the "inflamed" (vulnerable) plaques by scintigraphy using IL-2 labelled with (99m)Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. A total of 28 patients (18 men, 10 women, aged 55.2 ± 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of (99m)Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. Increased (99m)Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal (99m)Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 ± 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine (R = 0.22, p = 0.037), apolipoprotein B (apoB) (R = 0.31, p = 0.008), apoB to apoA-I ratio (R = 0.29, p = 0.012) and triglyceride concentration (R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 ± 0.5 vs 2.16 ± 0.68, p = 0.025) was revealed as well as a difference between values of T/nT ratio in groups of patients with values of apoB, soluble CD40 ligand and asymmetric dimethylarginine above and below median (3.18 ± 0.52 vs 2.16 ± 0.68, p = 0.031). No statistically significant association was found between T/nT ratio and mean value of either IMT or classic cardiovascular risk factors. Scintigraphy with the use of (99m)Tc-HYNIC-IL-2 can be a tool for inflamed atherosclerotic (vulnerable) plaque visualization within CCA in ESRD patients. Quantitative results of carotid artery scintigraphy with (99m)Tc-HYNIC-IL-2 correlate with serum concentration of selected cardiovascular risk markers.


Effectiveness and safety of nutritional supplements in the treatment of hereditary retinal dystrophies: a systematic review.
The hereditary retinal dystrophies (HRDs) are a group of genetically determined disorders that result in loss of the visual function. There is a lack of standard pharmacological treatments or widely accepted nutritional recommendations. The objective of this review is to summarise the scientific evidence on the effectiveness and safety of nutritional supplements for the treatment of HRDs. We conducted a scientific literature search on Medline and PreMedline, EMBASE, SCI-EXPANDED, SSCI, and The Cochrane Library up to August 2014. Experimental, quasi-experimental and controlled observational studies were selected. Eight studies were ultimately included, seven on retinitis pigmentosa (RP) and one on Best disease. Vitamin A, vitamin E, docosahexaenoic acid (DHA), lutein and β-carotene were assessed. A 15 000 IU daily dose of vitamin A was reported to have shown a small protective effect on the progression of RP, as was the use of the carotenoids lutein and β-carotene. Different DHA doses has no effect on RP or Best disease. No supplement showed severe adverse effects in the selected studies although strong evidence of toxicity exists for high doses of vitamin A and β-carotene in certain populations. The selected studies concluded that there may be a small beneficial effect of vitamin A, lutein and β-carotene on the progression of RP. The limited evidence available indicates some well-designed additional studies on combined supplements strategies may achieve more robust conclusions. Moreover, the scarcity of evidence available on the treatment of HRD other than RP with nutritional supplements supports the need for further research efforts.


Erratum to efficacy and safety of mecapegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer: a randomized, multicenter, active-controlled phase III trial.
[This corrects the article DOI: 10.21037/atm.2019.07.95.].


Regional differences in HIV prevalence and individual attitudes among service providers in China.
We examined the relationships between a region's HIV prevalence and HIV-related knowledge, perceived risk of HIV infection, perceived institutional support for HIV care, and avoidance attitude toward persons living with HIV (PLH) among service providers in China. Data were collected from 40 county-level hospitals in two provinces, including 1760 service providers. Multi-sample standardization and decomposition analysis was performed for HIV knowledge, perceived risk, institutional support, and avoidance attitude toward PLH. After adjusting for potential confounders, service providers from the province with higher HIV prevalence perceived a higher risk of contracting HIV at work, recognized more institutional support for HIV care, and reported a lower level of avoidance attitude toward PLH compared to those from the province with lower HIV prevalence. After confounding factors were standardized across provinces, occupational exposure experience was determined to be the strongest influence on the discrepancy of avoidance attitudes in the two provinces. Regional contextual factors could shape individual providers' attitudes and beliefs and impact the quality of care. Stigma reduction interventions need to be culturally tailored and region-specific.


Synthesis of calcium carbonate-loaded mesoporous SBA-15 nanocomposites for removal of phosphate from solution.
Removal of phosphate from water is very crucial for protecting the ecological environment since massive phosphorus fertilizers have been widely used and caused serious water deterioration. Thus, we fabricated a series of calcium carbonate-loaded mesoporous SBA-15 nanocomposites with different Ca:Si molar ratio (CaAS-x) as phosphorus adsorbents via a simple wet-impregnation method. The multiply approaches including X-ray diffraction (XRD), N2 physisorption, thermogravimetric mass spectrometry (TG-MS), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT-IR) were used to characterize the structure, morphology, and composition of mesoporous CaAS-x nanocomposites. The phosphate adsorption efficiency of the CaAS-x nanocomposites was studied through adsorption and desorption batch tests. Results showed that the increases of Ca:Si molar ratio (rCa:Si) improved the phosphate removal capacity of CaAS nanocomposites, especially CaAS with the optimum synthesis molar ratio of Ca:Si as 0.55 showed the high adsorption capacity of 92.0 mg·g-1 to high concentration of phosphate (> 200 mg·L-1). Note that the CaAS-0.55 had a fast exponentially increased adsorption capacity with increasing the phosphate concentration and correspondingly showed a much faster phosphate removal rate than pristine CaCO3. Apparently, mesoporous structure of SBA-15 contributed to high disperse of CaCO3 nanoparticles leading to the monolayer chemical adsorption complexation formation of phosphate calcium (i.e., =SPO4Ca, =CaHPO4-, and =CaPO4Ca0). Therefore, mesoporous CaAS-0.55 nanocomposite is an environmental-friendly adsorbent for effective removal of high concentration of phosphate in neutral contaminated wastewater.


Synergistic driving effects of risk factors on human brucellosis in Datong City, China: A dynamic perspective from spatial heterogeneity.
Brucellosis is a highly contagious zoonotic and systemic infectious disease caused by Brucella, which seriously affects public health and socioeconomic development worldwide. Particularly, in China accumulating eco-environmental changes and agricultural intensification have increased the expansion of human brucellosis (HB) infection. As a traditional animal husbandry area adjacent to Inner Mongolia, Datong City in northwestern China is characterized by a high HB incidence, demonstrating obvious variations in the risk pattern of HB infection in recent years. In this study, we built Bayesian spatiotemporal models to detect the transfer of high-risk clusters of HB occurrence in Datong from 2005 to 2020. Geographically and Temporally Weighted Regression and GeoDetector were employed to investigate the synergistic driving effects of multiple potential risk factors. Results confirmed an evident dynamic expansion of HB from the east to the west and south in Datong. The distribution of HB showed a negative correlation with urbanization level, economic development, population density, temperature, precipitation, and wind speed, while a positive correlation with the normalized difference vegetation index, and grassland/cropland cover areas. Especially, the local animal husbandry and related industries imposed a large influence on the spatiotemporal distribution of HB. This work strengthens the understanding of how HB spatial heterogeneity is driven by environmental factors, through which helpful insights can be provided for decision-makers to formulate and implement disease control strategies and policies for preventing the further spread of HB.


The political economy of health care: colonial Namibia 1915-1961.
The political economy of health care services in colonial Namibia during 1915-1961 closely reflected the extreme racial and class imbalance of power in a conquest state. The colonial power allocated to the indigent nine-tenths, the poorest nine-tenths of the people, an average 43% of the health care budget between 1922 and 1954. The League of Nations mandate proved toothless in pressuring the Mandatory power to rectify this or other inequalities.


Formation of the OOH(·) radical at steps of the boehmite surface and its inhibition by gallic acid: A theoretical study including DFT-based dynamics.
The ability of boehmite surface to stabilize reactive oxygen species (ROS) was investigated with density functional theory (DFT) calculations. We provide evidence that the O2(·-)radical is stabilized at the AlOOH boehmite terrace defect-free surface, and that step favors the formation of the OOH(·) radical without activation energy required. These tendencies are confirmed when considering the explicit presence of water solvent. We propose that gallic acid (GA), a non-expensive, non-toxic, natural product and radical scavenger, may form a full layer on the (101) stepped boehmite surface. The quenching of O2- to OOH(·) reaction on the GA-functionalized boehmite surface is investigated. It is shown that gallic acid passivates the surface and that the formation of the OOH(·) radical is consequently inhibited. The interaction of the GA-functionalized boehmite surface with water mimicking the body fluid is also investigated by means of DFT-based molecular dynamics simulations at room temperature. Hydrogen bonds between the functionalized GA layer and the immediate interfacial water are characterized.


Measurements of internal distance changes of the 30S ribosome using FRET with multiple donor-acceptor pairs: quantitative spectroscopic methods.
We present analytical and experimental procedures for determining distance changes within the 30 S subunit of the Escherichia coli ribosome using Förster resonance energy transfer (FRET). We discuss ways to contend with complexities when using FRET to measure distance changes within large multi-subunit macromolecular complexes, such as the ribosome. Complications can arise due to non-stoichiometric labeling of donor and acceptor probes, as well as environmental effects that are specific to each conjugation site. We show how to account for changes in extinction coefficients, quenching, labeling stoichiometry and other variations in the spectroscopic properties of the dye to enable more accurate calculation of distances from FRET data. We also discuss approximations that concern the orientation of the transition moments of the two dye molecules, as well as the impact of other errors in the measurement of absolute distances. Thirteen dye-pair locations with different distances using 18 independent FRET pairs conjugated to specific 30 S protein residues have been used to determine distance changes within the 30 S subunit upon association with the 50 S subunit, forming the 70 S ribosome. Here, we explain the spectroscopic methods we have used, which should be of general interest in studies that aim at obtaining quantitative distance information from FRET.


Insights into the selective inhibition of Candida albicans secreted aspartyl protease: a docking analysis study.
Severe fungal infections have taken precedence over other bacterial infections. Of the several fungal species, Candida albicans and others belonging to the genus Candida are responsible for several clinically important fungal infections. Emerging cases of drug resistance to the currently available drugs has limited the spectrum of currently available antifungal agents. Thus, it is imperative that new biochemical targets are identified so that better effective and selective agents can be developed. Many enzymes contribute towards the complex disease process of fungal infections; the secreted aspartyl protease (SAP), expressed both in vitro and during infection, has been implicated as one of the major virulence factors of C. albicans. Three-dimensional crystal structures of C. albicans SAP and closely related clinical isolate designated as SAP2X complexed with the same potent inhibitor A-70450 have been reported. Several analogues of A-70450 with potent C. albicans SAP2X inhibitory activity are also known. However, the structural effects of the binding of these compounds with the enzyme active site are not completely understood. Our efforts in this direction involve the docking analysis of C. albicans SAP2X inhibitors complexed with SAP2X enzyme, which is reported in this work. Docking analysis was performed on a set of molecules with differing selectivities and inhibitory potencies towards C. albicans, renin and cathepsin D. The structural effects of ligand binding were analyzed on the basis of hydrophobic and hydrogen bond interactions, binding energy analysis, interaction energies, rms deviations, etc. in the resulting energy-minimized structures of the receptor-ligand complexes. Structural analysis of the resulting models indicates that hydrophobic and hydrogen bonding interactions together with binding and interaction energies are responsible for selective inhibition of C. albicans SAP2X. Hydrophobic and hydrogen bonding interactions in the various subsites of the enzyme, contributing to both increase as well as decrease in selectivity of the molecules have been detailed. Hydrogen bonding interaction plays an important role for amino acid residues such as Gly-85, Asp-86, Asp-32, Asp-218, Tyr-225, Ala-133, and so on. Significant hydrophobic interactions with the S3, S2 and S2' subsites contribute to selectivity of the compounds. These molecular modeling analyses should, in our view, contribute for further development of selective C. albicans secreted aspartyl protease inhibitors.


Sharp edge artifacts and spurious coupling in EEG frequency comodulation measures.
Recent electroencephalogram (EEG), electrocorticogram (ECoG), and local field potential (LFP) observations suggest that distinct frequency bands interact. Numerous measures have been proposed to analyze such interactions, including the amplitude envelope modulation of high frequency activity by the phase or signal of low frequency activity. In this short communication, we describe how abrupt increases or decreases in voltage data may produce spurious coupling in these measures and suggest techniques to detect these effects.


Clinician Perspectives for Mental Health Delivery Following COVID-19 in Carceral Settings: A Pilot Study.
We aimed to understand clinician perspectives on mental healthcare delivery during COVID-19 and the utility of tele-mental health services in carceral settings. A survey was administered in November 2022 through the American College of Correctional Physicians listserv. A nationwide sample of 55 respondents included 78.2% male (n = 43) and 21.8% female (n = 12), 49.1% active clinicians (n = 27) and 50.9% medical directors (n = 28), with a median of 12 and mean of 14.5 years working in carceral settings. Most agreed that mental telehealth services could serve as a stopgap amid infection prevention measures and resource-limited settings with an increasing role moving forward (80.0%, n = 44) but may not be sufficient to replace in-person services completely. Access to mental healthcare is vital in helping achieve optimal health during incarceration. Most clinicians in a nationwide survey report an essential role of mental telehealth in the future, although they vary in beliefs on the present implementation. Future efforts should further identify facilitators and barriers and bolster delivery models, particularly via e-health.


The fit between journals and theses.
The titles of a substantial sample of articles related to speech pathology and audiology over a period of 21 years were catalogued under one or more of 10 categories, e.g., normal audition, defective phonation, and the like. The titles of theses and dissertations in this field of six universities of Ohio over the same period were also catalogued. The articles appeared in 17 journals. The journals were treated as seven groups of "related" journals. The total output of journals was stable over the period studied; a "group" of journals tended to be consistent with itself over successive 3-year periods; the seven groups of journals tended to be unique, and not to replicate each other. The topics treated in the journals were accepted as a criterion for contemporaneousness. The student output of the universities varied in contemporaneousness from one school to another, ranging upward to r = 0.98 (10 categories). The overall correlation between the student and the journal outputs was r = 0.79.


[Electromyographic evaluation of muscular tension in dysfunctional subjects in relation to normal subjects].
Electromyography has been used to analyse the myoelectric activity of the masticatory muscles in 130 dysfunctional patients in comparison with normal subjects. Of the muscles examined, those presenting greater basal tension were also identified. Myoelectric activity proved greater, at postural values, in dysfunctional patients; by contrast, subjects without craniomandibular symptomatology presented normally low initial values. As for the analysis of the muscular group presenting greater tension, analysis of the results did not produce statistically significant percentages pointing to the prevalence of one muscular group over another.


Blood sampling methodology is crucial for precise measurement of plasma catecholamines concentrations in mice.
Epinephrine (E) and norepinephrine (NE) play a major role in regulating metabolism and cardiovascular physiology. Both are secreted in response to stress and their measurement in plasma allows the study of sympathoadrenal function. Several studies investigating sympathoadrenal physiology are conducted using mice. Review of the literature revealed that basal mouse NE and E plasma concentrations range within 4-140 nM depending on the blood sampling method. Such variability doesn't allow study comparison and may conceal catecholamine variations in response to stress. Therefore, our aim was to determine a reliable sampling method to measure mouse plasma catecholamine concentrations. Results showed that arterial catheterization is the most accurate sampling method: E and NE basal levels were similar to those found in humans (1.1+/-0.3 nM and 4.1+/-0.5 nM, respectively). Retro-orbital bleeding led to analogous results. On the contrary, decapitation was stressful for mice and consequently NE and E concentrations were high (24.6+/-2.7 nM and 27.3+/-3.8 nM, respectively). These different bleeding methods were compared in terms of their ability to detect sympathoadrenal system stimulation (cold-pressure test). With catheter and retro-orbital samplings the expected increase in NE and E levels was easily perceived. In contrast, with decapitation no significant change in E was detected. In conclusion, arterial-catheter and retro-orbital blood sampling methods appear to be the most accurate procedures for studying the sympathetic nervous system in mice in both unstressed and stressed conditions.


Osteoarthritis and its management - Epidemiology, nutritional aspects and environmental factors.
Osteoarthritis (OA) is the most prevalent chronic rheumatic diseases worldwide, with a strong impact on individual and population health. OA is a clinically heterogeneous disease presenting with different clinical phenotypes recognising systemic and local risk factors. The pathogenesis is multifactorial including constitutive features of the joint, non-modifiable and modifiable risk factors. Epidemiological studies highlight the link between metabolic syndrome and OA and the effect of interplay between immunological and metabolic processes is getting increasing emphasis because of to the discovery that metabolic syndrome is implicated in OA pathogenesis and progression. In addition, recent findings suggest a potential role of dietary factors in susceptibility and progression of OA. In this review, we summarise the most robust evidence on epidemiology and classical risk factors OA, also exploring the most recent evidence on metabolic changes and Mediterranean diet for OA as a possible target to impact on the natural history of the disease.


Recent relocation and decreased survival following a cancer diagnosis.
To determine the impact of recent relocation prior to a cancer diagnosis on cancer-specific outcomes. We identified 272,718 patients with two different entries in the Surveillance, Epidemiology, and End Results database within 3years of each other. Those who had relocated to a different county between entries were identified and we determined the risk of stage IV disease or cancer-specific mortality among relocators and non-relocators after adjusting for other patient-specific demographic and clinical factors. A total of 4639 (1.7%) patients relocated to a new county within 3years prior to a second cancer diagnosis and 268,079 (98.3%) patients did not. Patients who had relocated to a new area were more likely to be diagnosed with stage IV cancer (25.2% vs. 20.8%; adjusted odds ratio=1.27; 95% confidence interval [CI], 1.18-1.37; P<0.001), and had an increased risk of 10-year cancer-specific mortality (20.9% vs. 17.9%; adjusted hazard ratio 1.26; 95% CI, 1.17-1.36; P<0.001). These results suggest that recent relocation to a new county prior to a cancer diagnosis is associated with an increased risk of late-stage presentation and worse cancer-specific mortality.