Patronage, partnership, voluntarism: Community-based health insurance and the improvisation of universal health coverage in Senegal.
The turn towards Universal Health Coverage (UHC) in the past decade raises the question of the role of the state, following years of state withdrawal and a fragmented approach to public health. Senegal introduced its version of UHC, Couverture Maladie Universelle (CMU) in 2013 and this paper explores early efforts to fund it through the establishment of community-based health insurance (CBHI). The paper draws on ethnographic research at mutual health organisations, or mutuelles de santé as they are commonly referred to in francophone countries, which manage CBHI. The research was carried out as part of broader doctoral fieldwork on poverty and social protection in the capital, Dakar, in 2017-18. Responding to recent calls for the move away from the voluntary nature of CBHI with government subsidies and the professionalisation of management, this paper considers the financial strain that mutuelles were under. By drawing on the concept of 'improvisation' as it has come to be employed in recent ethnographies of health infrastructure in contexts of scarcity, the paper attends to the ways in which mutuelles and the voluntary workers that run them sought alternative forms of support, with a particular focus on patronage and partnership. I argue that what might appear to be very minimal gestures of support and material investment serve to maintain a sense of hope and potential in CMU, one however that is fragile and potentially unsustainable.


The prevalence of hypertension and its association with other cardiovascular disease risk factors in a representative sample of the Lebanese population.
Hypertension is a well-known major risk factor for cardiovascular diseases. This study has been designed to assess the prevalence of hypertension, its co-occurrence with other cardiovascular risk factors and its association with cardiovascular diseases in a representative sample of Lebanese population. A pretested questionnaire was administered to 2125 adults aged equal or above 30 years old from all regions in Lebanon and proportionate with the respective population density. Data revealed that 23.1% of the respondents admitted being hypertensive, with no statistically significant difference between male and female patients. Prevalence of hypertension increased with age (P < 0.01) and hypertension tended to occur more in the less educated and the unemployed (P < 0.01). Only 45.7% of hypertensive patients followed a low fat diet while 14.7% exercised daily. The prevalence of hypertension increased significantly with an increase in body mass index particularly in female patients. Among the hypertensive respondents, 23.9% were diabetic, 38.1% were hyperlipidaemic and 9.1% were both diabetic and hyperlipidaemic. Co-occurrence of hypertension with diabetes, hyperlipidaemia or both was more common in female patients compared to male patients. In addition, stroke, myocardial infarction (MI) and atherothrombosis occurred in hypertensive respondents at rates of 2.4, 4.3 and 9.5%, respectively. Hypertensive female patients reported more stroke and atherothrombotic episodes compared to male patients, whereas hypertensive male patients had more MIs. Based on these results it is very important to address the issue of lifestyle modification for the prevention and treatment of hypertension and awareness campaigns should stress the fact that cardiovascular diseases are not only restricted to men.


Megacraspedus cottiensis sp. nov. (Lepidoptera, Gelechiidae) from northern Italy - a case of taxonomic confusion.
Megacraspedus cottiensis sp. nov. is described from the western Alps (prov. Torino, Italy). The dorsal habitus and genitalia for both the male and brachypterous female are provided. The new species belongs to the M. faunierensis species group based on genitalia morphology and DNA barcodes, and was hitherto confused with M. neli Huemer & Karsholt, 2018 from the southwestern Alps. However, it clearly differs in morphology and DNA barcode sequences from that species and from M. faunierensis Huemer & Karsholt, 2018. The new species is suspected of being a regional endemic of the Cottian Alps.


Origin and fate of rat plasma cholesterol in vivo. Modelling of cholesterol movements between plasma and organs.
A cholesterol system model was developed in the rat following a single injection of red cells containing free (unesterified) [3H]cholesterol. The radioactivity of free and esterified cholesterol in the different parts of the system was measured during the 48 h following tracer introduction. The model consisted of seven compartments (red cell free cholesterol, plasma and liver free and esterified cholesterol, total cholesterol in the rapidly and slowly exchangeable carcass pools). The model was validated by the similarity between simulated and experimental values during the 48 h following tracer introduction. Both the fractional rate of cholesterol esterification in the plasma (0.44 h-1) and liver (0.01 h-1) and the fractional exchange rate of free cholesterol from the plasma towards the various organs (particularly 3 h-1 towards the liver for a total of 7 h-1) can be estimated with this model. The results show that cholesterol movements between the plasma and the different organs take place mainly through intense free cholesterol exchanges, resulting in a low net flux.


Targeting USP9X-AMPK Axis in ARID1A-Deficient Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor with high morbidity and mortality. AT-rich interaction domain 1A (ARID1A) accounts for up to 10% of mutations in liver cancer, however, its role in HCC remains controversial, and no targeted therapy has been established. The expression of ARID1A in clinical samples was examined by Western blot and immunohistochemical staining. ARID1A was knocked out by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) in HCC cell lines, and the effects of glucose deprivation on cell viability, proliferation, and apoptosis were measured. Mass spectrometry analysis was used to find ARID1A-interacting proteins, and the result was verified by co-immunoprecipitation and Glutathione S Transferase (GST) pull-down. The regulation of ARID1A target gene USP9X was investigated by chromatin immunoprecipitation, Glutathione S Transferase (GST) pull-down, luciferase reporter assay, and so forth. Finally, drug treatments were performed to explore the therapeutic potential of the agents targeting ARID1A-deficient HCC in vitro and in vivo. Our study has shown that ARID1A loss protected cells from glucose deprivation-induced cell death. A mechanism study disclosed that AIRD1A recruited histone deacetylase 1 via its C-terminal region DUF3518 to the promoter of USP9X, resulting in down-regulation of USP9X and its target protein kinase AMP-activated catalytic subunit α2 (PRKAA2). ARID1A knockout and a 1989∗ truncation mutant in HCC abolished this effect, increased the levels of H3K9 and H3K27 acetylation at the USP9X promoter, and up-regulated the expression of USP9X and protein kinase AMP-activated catalytic subunit α2 (PRKAA2), which mediated the adaptation of tumor cells to glucose starvation. Compound C dramatically inhibited the growth of ARID1A-deficient tumors and prolongs the survival of tumor-bearing mice. HCC patients with ARID1A mutation may benefit from synthetic lethal therapy targeting the ubiquitin-specific peptidase 9 X-linked (USP9X)-adenosine 5'-monophosphate-activated protein kinase (AMPK) axis.


Echophonocardiographic estimation of pulmonary capillary pressure in acute myocardial infarction.
Non-invasive estimation of pulmonary capillary wedge (PCW) pressure by an echophonocardiographic technique is reported. The ratio of time interval from the Q-wave to the C-point (echocardiogram) (Q-C) and from aortic closing (A2) to the E-point (A2-E) correlated well with the measured PCW pressure (r = 0.89; P = 0.001). When these two intervals were subtracted (A2-E)-(Q-C) the correlation was r = -0.90 (P = 0.001).


Zhizhu Kuanzhong Capsule in treating patients with functional dyspepsia postprandial distress syndrome: study protocol for a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial.
Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders. Based on the various symptoms present in patients with functional dyspepsia postprandial distress syndrome (FD-PDS), routine agents such as acid suppressants, prokinetic drugs, and centrally acting drugs, offer limited treatment choices with potential side effects. As a preliminary clinical trial showed that the marketed product Zhizhu Kuanzhong Capsule (ZZKZ) can improve symptoms in FD-PDS patients, our study aims to provide further evidence on the clinical efficacy and safety of ZZKZ in the treatment of patients with FD-PDS. In this multicenter, randomized, patient- and investigator-blinded, placebo-controlled, parallel-group clinical trial, we will recruit patients with FD-PDS from 18 hospitals in China and Australia. The trial will enroll patients with FD-PDS based on the Rome IV diagnostic criteria. A total of 480 eligible patients will be randomized 1:1 into either ZZKZ or placebo group with 8 weeks of treatment and 4 weeks of follow-up. The primary endpoint will be measured by a self-rated Visual Analogue Score (VAS) for the degree of discomfort with both symptoms of postprandial fullness and early satiation, recorded once a day and 7 days a week. The primary analysis will aim to compare the response rate for FD-PDS VAS score between the groups before and after 8 weeks of treatment with an alpha level of 0.05 (2-sided). This trial aims to strengthen the evidence for the efficacy and safety of ZZKZ, a marketed product, in treating FD-PDS. Compared to the previous clinical trial that targeted FD-PDS, this trial will have an 8-week double-blind treatment period to investigate the effect of long-term mediation through comparison with the placebo group. ClinicalTrials.gov NCT03825692 . Registered on 28 January 2019.


A pilot study of stereotactic boost for malignant epidural spinal cord compression: clinical significance and initial dosimetric evaluation.
Metastatic epidural spinal cord compression (MESCC) is a devastating complication of advanced malignancy, which can result in neurologic complications and significant deterioration in overall function and quality of life. Most patients are not candidates for optimal surgical decompression and as a result, receive urgent 3D conformal radiotherapy (3DCRT) to prevent or attempt to reverse neurologic progression. Multiple trials indicate that response and ambulatory rates after 3DCRT are inferior to surgery. The advent of stereotactic body radiation therapy (SBRT) has created a method with which a "radiosurgical decompression" boost may facilitate improve outcomes for MESCC patients. We are conducting a pilot study to investigate SBRT boost after urgent 3D CRT for patients with MESCC. The aim of the study is to establish feasibility of this two-phase treatment regimen, and secondarily to characterize post-treatment ambulation status, motor response, pain control, quality of life and survival. We describe the study protocol and present a case report of one patient. A quality assurance review was conducted after the first seven patients, and resultant dose-constraints were revised to improve safety and feasibility of planning through more conservative organ at risk constraints. There have been no severe adverse events (grade 3-5) to date. We have illustrated clinical and dosimetric data of an example case, where a patient regained full strength and ambulatory capacity. Our study aims to determine if SBRT is a feasible option in addition to standard 3DCRT for MESCC patients, with the goal to consider future randomized trials if successful. Having a robust quality assurance process in this study ensures translatability going forward if future trials with multicenter and increased patient representation are to be considered. clinicaltrials.gov; registration no. NCT03529708; https://clinicaltrials.gov/ct2/show/NCT03529708 ; First posted May 18, 2018.


A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture.
While human induced pluripotent stem cells (hiPSCs) have promising applications in regenerative medicine, most of the hiPSC lines available today are not suitable for clinical applications due to contamination with nonhuman materials, such as sialic acid, and potential pathogens from animal-product-containing cell culture systems. Although several xeno-free cell culture systems have been established recently, their use of human fibroblasts as feeders reduces the clinical potential of hiPSCs due to batch-to-batch variation in the feeders and time-consuming preparation processes. In this study, we have developed a xeno-free and feeder-cell-free human embryonic stem cell (hESC)/hiPSC culture system using human plasma and human placenta extracts. The system maintains the self-renewing capacity and pluripotency of hESCs for more than 40 passages. Human iPSCs were also derived from human dermal fibroblasts using this culture system by overexpressing three transcription factors-Oct4, Sox2 and Nanog. The culture system developed here is inexpensive and suitable for large scale production.


Do spinal cord injuries adversely affect serum lipoprotein profiles?
Previous reports indicate that dyslipidemia is very common in persons with spinal cord injury. This study aimed to examine the relationship between spinal cord injury and serum lipoprotein profiles. We assessed 28 healthy control subjects matched for age and sex and 60 persons (46 men and 14 women; mean age, 28.1 years) with spinal cord injury having a mean duration of injury of 3.6 +/- 0.8 years (range, 1-13 years). Serum low-density lipoprotein cholesterol level was higher (109 +/- 37, 91 +/- 23.7 mg/dL, respectively) (p = 0.04) and serum high-density lipoprotein cholesterol level was lower (33 +/- 7.1, 44 +/- 7.4 mg/dL, respectively) (p < 0.001) in the patients with spinal cord injury than in the control. Apolipoprotein A-I level was significantly low (94 +/- 10.3, 103 +/- 11.5 mg/dl) (p = 0.003) and apolipoprotein B level was significantly high (93 +/- 15.6, 81 +/- 13.7mg/dL) (p = 0.004) in the group of spinal cord injury. No significant difference was observed the other parameters of these two groups. Our results have shown that serum lipoprotein level should not be ignored for the follow-up of the patients with spinal cord injury.


Development and validation of questionnaires for eating-related distress among advanced cancer patients and families.
Eating-related distress (ERD) is one type of psychosocial distress among advanced cancer patients and family caregivers. Its alleviation is a key issue in palliative care; however, there is no validated tool for measuring ERD. The purpose of this study was to validate tools for evaluating ERD among patients and family caregivers. The study consisted of a development and validation/retest phase. In the development phase, we made preliminary questionnaires for patients and family caregivers. After face validity and content validity, we performed an exploratory factor analysis and discussed the final adoption of items. In the validation/retest phase, we examined factor validity with an exploratory factor analysis. We calculated Pearson's correlation coefficients between the questionnaire for patients, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cachexia 24 (EORTC QLQ-CAX24) and Pearson's correlation coefficients between the questionnaire for family caregivers and the Caregiver Quality of Life Index-Cancer (CQOLC) for concurrent validity. We calculated Cronbach's alpha coefficients (Cronbach's alpha) and intraclass correlation coefficients (ICCs) for internal consistency and test-retest reliability. We performed the Mann-Whitney U test between the questionnaires and cancer cachexia based on criteria from the international consensus for known-group validity. In the development phase, 162 pairs of patients and family caregivers were asked to participate, and 144 patients and 106 family caregivers responded. In the validation/retest phase, 333 pairs of patients and family caregivers were asked to participate, and 234 patients and 152 family caregivers responded. Overall, 183 patients and 112 family caregivers did the retest. Seven conceptual groups were extracted for the ERD among patients and family caregivers, respectively. Patient factors 1-7 correlated with FAACT ACS (r = -0.63, -0.43, -0.55, -0.40, -0.38, -0.54, -0.38, respectively) and EORTC QLQ-CAX24 (r = 0.58, 0.40, 0.60, 0.49, 0.38, 0.59, 0.42, respectively). Family factors 1-7 correlated with CQOLC (r = -0.34, -0.30, -0.37, -0.37, -0.46, -0.42, -0.40, respectively). The values of Cronbach's alpha and ICC of each factor and all factors of patients ranged from 0.84 to 0.96 and 0.67 to 0.83, respectively. Those of each factor and all factors of family caregivers ranged from 0.84 to 0.96 and 0.63 to 0.84, respectively. The cachexia group of patients had significantly higher scores than the non-cachexia group for each factor and all factors. Newly developed tools for measuring ERD experienced by advanced cancer patients and family caregivers have been validated.


Muscarinic receptors of the albino rabbit ciliary process.
Muscarinic receptor binding sites were identified in membranes prepared from albino rabbit ciliary processes, using the muscarinic antagonist [3H]L-quinuclidinyl benzylate as the radioligand. Analysis of saturation binding experiments demonstrated that [3H]L-quinuclidinyl benzylate bound to an apparent homogeneous population of binding sites with a Kd value of 6.4 pm and a Bmax value of 155 fmol mg-1 protein. Seventy percent (70%) of binding sites showed high affinity for pirenzepine, i.e. belonged to the M1 subtype. In contrast, AF-DX 116 was unable to discriminate between subtypes of muscarinic binding sites in this tissue. Carbachol caused a dose-dependent increase in phosphatidylinositol turnover (EC50 = 154 microM) in ciliary processes. A maximum stimulation of 652% of basal activity was obtained following a 45 min incubation with 10 mM carbachol. The potency of muscarinic antagonists to block the carbachol-induced response was comparable to that found for M1 receptors in other tissues. Oxotremorine and pilocarpine behaved like partial agonists in this assay. The carbachol-induced increase in phosphatidylinositol turnover was also observed in a suspension of epithelial cells from ciliary processes and it was blocked by atropine; thus, indicating the presence of muscarinic receptors functionally coupled to phosphatidylinositol turnover in these cells.


Effective immunity to dental caries: selective induction of secretory immunity by oral administration of Streptococcus mutans in rodents.
1) The selective induction of secretory antibody is antigen dose dependent. A dose of 10(7) or 10(8) S. mutans CFU (per gram of diet) elicited a significant response, while a higher dose (10(9) CFU/gram) resulted in an apparent state of unresponsiveness. 2) A lowly virulent mutant of S. mutans 6715 (C4) induced protective s-IgA antibodies against challenge with a highly virulent species (C211). Cross protection among serotypes of S. mutans has been achieved. 3) Bovine milk with antibodies to S. mutans significantly reduced the level of caries lesions in rats fed this lyophilized milk and challenged with the homologous, virulent S. mutans strains.


Could high continuity of care (COC) have a negative impact on subjective health of hypertensive patients? A Japanese perspective.
Cardiovascular diseases, such as stroke and ischemic heart disease attributable to hypertension, are major causes of premature death in Japan and worldwide. Nevertheless, a low rate of blood pressure control among hypertensive patients has been observed in most countries. No previous studies have explored the effectiveness of physician visits among hypertensive patients in Japan. To quantify the effects of persistence in physician visits among hypertensive patients, we evaluated the causal effect of physician visits on the health of hypertensive patients. We used 16 waves of nationally representative longitudinal data drawn from the Longitudinal Survey of Middle-aged and Elderly Persons in Japan (2005-2020). To examine the causal effect of physician visits on patients' health outcomes, we used inverse probability treatment weights and doubly robust estimation and obtained the estimates of the average treatment effects on the treated (ATETs). Covariates were well balanced among patients who had physician visits during the past two consecutive years (N = 67,210; 64.9% among hypertensive patients). The estimated ATETs suggest that three consecutive years of physician visits had a negative impact on poor subjective health. Furthermore, patients without habitual exercise tended to not continue physician visits and perceived poor subjective health. Although the impact of frequent physician visits on blood pressure stability remains uncertain, regular appointments every 30 days can be effective for individuals with hypertension, particularly if they receive continuous instruction from their family physician. Because it is important for physicians to strengthen hypertensive patients' blood pressure control, promoting consecutive physician visits to hypertensive patients with diabetes, lower educational attainment, or smoking habits is needed.


Thickness sensing of hMSCs on collagen gel directs stem cell fate.
Mechanically compliant substrate provides crucial biomechanical cues for multipotent stem cells to regulate cellular fates such as differentiation, proliferation and maintenance of their phenotype. Effective modulus of which cells sense is not only determined by intrinsic mechanical properties of the substrate, but also the thickness of substrate. From our study, it was found that interference from underlying rigid support at hundreds of microns away could induce significant cellular response. Human mesenchymal stem cells (hMSCs) were cultured on compliant biological gel, collagen type I, of different thickness but identical ECM composition and local stiffness. The cells sensed the thin gel (130 μm) as having a higher effective modulus than the thick gel (1440 μm) and this was reflected in their changes in morphology, actin fibers structure, proliferation and tissue specific gene expression. Commitment into neuronal lineage was observed on the thin gel only. Conversely, the thick gel (1440 μm) was found to act like a substrate with lower effective modulus that inhibited actin fiber polymerization. Stem cells on the thick substrate did not express tissue specific genes and remained at their quiescent state. This study highlighted the need to consider not only the local modulus but also the thickness of biopolymer gel coating during modulation of cellular responses.


Impact of atherosclerosis and age on Doppler sonographic parameters in the diagnosis of renal artery stenosis.
The purpose of this study was to investigate the influence of atherosclerosis and age on 4 representative Doppler parameters in the diagnosis of renal artery stenosis. The 4 parameters, renal peak systolic velocity (PSV), renal-aortic ratio, renal-interlobar ratio, and acceleration time, were measured in 208 patients before angiography. The 208 patients were divided into groups according to age and atherosclerosis stratification. The Student t test, 1-way analysis of variance, and the χ(2) test were used to compare all 4 parameters and clinical characteristics. The optimal cutoff values were determined by receiver operating characteristic curves. The diagnostic concordance between atherosclerosis and age strata was evaluated by the Cohen κ coefficient. Of the 416 renal arteries shown on Doppler sonography, 204 had a diagnosis of renal artery stenosis and 19 as occlusion on angiography. The optimal cutoff values for the renal-aortic ratio and renal-interlobar ratio in the groups aged 46 years or older and younger than 46 years were much different (2.3 versus 1.4 and 5.1 versus 6.5, respectively), whereas those for the renal PSV and acceleration time were close to each other or the same (170 versus 180 cm/s and 51 versus 51 milliseconds). The κ coefficients for the renal PSV, renal-interlobar ratio, acceleration time, and renal-aortic ratio between the atherosclerosis and age strata were 0.93, 0.99, 1.00, and 0.71. Atherosclerosis and age show comparable influences on Doppler parameters in the diagnosis of renal artery stenosis. For clinical convenience, cutoff values may be separately established on the basis of a 46-year-old borderline for the renal-aortic ratio and renal-interlobar ratio, although this process is not necessary for the renal PSV and acceleration time.


The effects of the modulation of the fibronectin-binding capacity of fibrin by thrombin on osteoblast differentiation.
Fibrin is a natural provisional matrix involved in wound healing and is widely utilized for tissue regeneration. The biological performance of fibrin is largely dependent on its composition and related structures. In this study, we examined the effect of thrombin, which is engaged with fibrin, on osteoblast differentiation and its mode of action. Fibrin matrices were prepared with different concentrations of thrombin, and MC3T3-E1 pre-osteoblasts were cultured on the fibrin matrices. Thrombin-promoted fibrin-enhanced osteoblast differentiation in a dose-dependent manner, as confirmed by the extent of calcium deposition, alkaline phosphatase activity, and the level of Runx2. The synthetic activating peptide of protease-activated receptor 1 (PAR1), a prototype receptor of thrombin in osteoblast, did not alter the level of Runx2. Instead, the thrombin that was engaged with fibrin in a dose-dependent manner increased the phosphorylation of integrins β1 and β3. The integrin-blocking peptide RGDS reduced the thrombin-enhanced Runx2 in the cells grown on fibrin, whereas the non-functional peptide RGES did not change the level of Runx2. Furthermore, thrombin dose-dependently increased the fibronectin-binding of fibrin. The thrombin-induced integrin phosphorylation and Runx2 expression were also attenuated through the use of a blocking peptide to inhibit the binding of fibronectin to fibrin. The results in this study provide evidence that thrombin engaged with fibrin accelerates osteoblast differentiation via integrins but not PAR1 by modulating the fibronectin-binding capacity of fibrin.


Vimentin and cytokeratin: Good alone, bad together.
The cytoskeleton plays an integral role in maintaining the integrity of epithelial cells. Epithelial cells primarily employ cytokeratin in their cytoskeleton, whereas mesenchymal cells use vimentin. During the epithelial-mesenchymal transition (EMT), cytokeratin-positive epithelial cells begin to express vimentin. EMT induces stem cell properties and drives metastasis, chemoresistance, and tumor relapse. Most studies of the functions of cytokeratin and vimentin have relied on the use of either epithelial or mesenchymal cell types. However, it is important to understand how these two cytoskeleton intermediate filaments function when co-expressed in cells undergoing EMT. Here, we discuss the individual and shared functions of cytokeratin and vimentin that coalesce during EMT and how alterations in intermediate filament expression influence carcinoma progression.


Linkage between the loci for peptidase D and cytochrome P-450 (CYP1) on chromosome 19.
Families segregating for PEPD have been investigated for linkage between PEPD and CYP1. The results provide evidence for close linkage between PEPD and CYP1 in males.


Small cytoplasmic antigens from Pseudomonas aeruginosa stimulate gammadelta T lymphocytes.
Gammadelta T lymphocytes respond to different bacterial antigens and transformed cells. The antigenic molecules responsible for this activity have been studied extensively in antigenic preparations from Mycobacterium. We describe here the in vitro effect of Pseudomonas aeruginosa on gammadelta T lymphocytes and the properties of the implicated compounds. We found a preferential gammadelta T-cell expansion when we used heat-treated P. aeruginosa preparations and a dose-dependent inhibition of proliferation of peripheral blood mononuclear cells (PBMC) when non-heat-treated antigens were studied. This expansion corresponded to a Vgamma9-positive subpopulation. In contrast to alphabeta T lymphocytes, the highest stimulatory activity was restricted to very small cytosolic compounds. This activity was protease resistant and phosphatase sensitive and always dependent on interleukin (IL)-2 or alphabeta T-cell activation. We concluded that the antigenic molecules from P. aeruginosa that activated gammadelta T lymphocytes were small, non-peptidic, phosphorylated compounds, similar to those previously described from Mycobacterium.


Total subperiosteal resection treatment of solitary bone cysts of the humerus.
The solitary bone cyst is most frequently located in the upper arm and the average age of the affected patients is between 7 and 9 years, thus perceptibly lower than in cases where solitary bone cyst occurs elsewhere, where the average age is 15. The tendency towards recurrence before 10 years of age is twice as great as the tendency after that age. Investigation of the results obtained from the treatment of 26 patients suffering from solitary bone cyst of the humerus showed a recurrence rate of 55% after curettage and filling-in of the defect with cancellous bone grafts, whereas after total subperiosteal resection and bridging the defect with an autologous tibia graft the corresponding recurrence frequency was 7%. The average duration of the plaster cast fixing period after resection treatment was 18 days longer than after curettage, but the low rate of recurrence in the first-mentioned case makes up for this disadvantage. It is absolutely essential to retain the periosteum in cases of cyst resections. The defect is bridged over by an autologous tibia graft, but fibula grafts are also suitable for bridging the defect. Osteosyntheses are not necessary with latent cysts. In the case of active cysts screws, wire loops, Kirschner wires, and thin Küntscher nails can be used as temporary stabilisation means. Plate osteosyntheses constitute an exception. Complete removal of the cyst by resection is the most certain prophylactic method against recurrence, and hence the most reliable form of treatment of the solitary bone cyst of the humerus.


Patient safety in home health care: a grounded theory study.
The home environment is designed for living, not for professional care. For this reason, safe patient care is one of the most important challenges of home health care. Despite abundant research on safe care, there is still little understanding of safety issues in home care. The aim of the present study was to explain the process of safe patient care in home health care. A qualitative, grounded theory study was conducted based on the approach proposed by Corbin & Strauss in 2015. In total, 22 interviews were conducted with 16 participants including 9 home care nurses, 2 home care nursing assistants, 1 home care inspector, 1 home care physician and 3 family caregivers in Tehran, Iran. Four observation sessions were conducted in different homes. Purposeful sampling was used followed by theoretical sampling from August 2020-July 2022. Data analysis was carried out based on the approach proposed by Corbin & Strauss in 2015. The results showed that the healthcare members (nurses, family caregivers, patients and home care centers) used the model of safe patient care in home health care based on four assessment methods, i.e. prevention, foresight, establishment of safety and verification. The core variable in this process is foresight-based care. The results of this study showed that the key to safe patient care in home health care, which helps to maintain patient safety and prevent threats to safe care, is the foresight of healthcare members, which is essential for identifying threats to safe care considering the many risks of home health care.


Generation of reactive oxygen species by blood monocytes during acute Plasmodium knowlesi infection in rhesus monkeys.
The status and kinetics of monocyte activation during acute P. knowlesi infection was investigated by latex-induced, luminol-dependent chemiluminescence (CL) response. The contribution of various reactive oxygen species (ROS) to CL response was estimated before infection and at peak parasitaemia (day 7 post infection) by using scavengers of ROS (benzoate, catalase and superoxide dismutase). The chemiluminescence index (CLI) was not found to be significantly different from controls on day 2 postinfection, but was significantly higher on days 5 and 7 postinfection. Hydroxyl radical (OH.) production was considerably elevated, whereas superoxide anion (O2-.) and hydrogen peroxide (H2O2) production dropped following infection. These changes in generation of ROS are discussed in relation to the progression of parasitaemia to high levels, immunopathology and immunosuppression during acute P. knowlesi infection.


Synthesis, evaluation and molecular modeling of cyclic tetrapeptide histone deacetylase inhibitors as anticancer agents.
Histone deacetylase inhibitors (HDACIs) are a promising class of anticancer agents. To examine whether a slight change in the recognition domain could alter their inhibitory activity, we synthesized a series of cyclo(-L-Am7(S2Py)-Aib-L-Phe(n-Me)-D-Pro)derivatives and evaluated their HDAC inhibitory and anticancer activities. The peptides exhibited potent HDAC inhibitory activity and inhibited three human cancer cell lines with IC₅₀ in the micromolar range. Docking and molecular dynamics simulation were conducted to explore the interaction mechanisms of class I and II HDACs with these inhibitors. It revealed that the zinc ion in the active site coordinated five atoms of HDACs and the sulfur atom of the inhibitor. The metal binding domains of these compounds interacted with HDAC2, and the surface recognition domains of these compounds interacted with HDAC4 through hydrogen bonding. The hydrophobic interactions also provided favorable contributions to stabilize the complexes. The results obtained from this study would be helpful for us to design some novel cyclic tetrapeptides that may act as potent HDACIs.


Pregnancy-related pelvic girdle pain: intertester reliability of 3 tests to determine asymmetric mobility of the sacroiliac joints.
Several tests have been developed to determine the extent of sacroiliac asymmetry during pregnancy-related pelvic girdle pain (PGP). This blinded control study investigated the intertester reliability of 3 such tests used in PGP. A total of 62 women (ages 20-40 years) were recruited from regional obstetric practices and subsequently divided into 3 groups: (1) 20 women without PGP who were pregnant for more than 20 weeks, (2) 22 women with PGP who were pregnant for more than 20 weeks, and (3) a control group of 20 women who were not pregnant and had no back pain or PGP. All tests were performed by 2 physiotherapists independently of each other and blinded to each other's results. The 3 tests were the thumb-posterior superior iliac spines test, the heel-bank test, and the abduction test. To determine the level of agreement between the 2 testers, kappa values were calculated. The overall kappa is 0.30 (range, -0.22 to 0.83), which is considered as a poor agreement. The percentage agreement per test/category ranged from 45% to 95%. This study of 3 tests used to determine asymmetry of the sacroiliac joints in women with pregnancy-related PGP showed them to have a poor intertester reliability.


Monkeypox Virus Infections.
Monkeypox is an uncommon viral zoonosis caused by the monkeypox virus (MPV), a member of the genus Orthopoxvirus. MPV is a large, complex, double-stranded DNA virus of the chordopoxvirus family. MPV is endemic in central and western Africa and is a classic zoonosis acquired through contact with infected rodents and squirrels. Observational studies of human monkeypox in central and western Africa have revealed that MPV infection has an incubation period of 10-14 days and a period of infectivity during the first week of rash. MPV enters the body through skin abrasions, the upper respiratory tract mucosa, or by ingestion. During primary viremia, the virus migrates to regional lymph nodes and then disseminates throughout the body. Vaccination with vaccinia virus (smallpox vaccine) is highly protective (around 85%) against MPV infection. Post-exposure smallpox vaccination is indicated for persons who are at high risk of MPV infection, including those investigating animal or human monkeypox cases, health care workers caring for infected patients, and laboratory workers who handle specimens that may contain MPV.


Streptozotocin‑induced diabetic mice exhibit reduced experimental choroidal neovascularization but not corneal neovascularization.
The present study aimed to investigate the effects of diabetes mellitus (DM) on the generation of experimental corneal neovascularization (CrNV) and choroidal neovascularization (ChNV). Diabetes was induced in mice by intraperitoneal injection of streptozotocin (STZ). Experimental CrNV and ChNV were induced by alkali injury and laser photocoagulation, respectively. CrNV and ChNV were compared between the STZ‑induced diabetic mice and control mice two weeks after injury. Relative expression of angiogenic factors was quantified by reverse transcription‑quantitative polymerase chain reaction, and progenitor cell or macrophage accumulation in the early phase following injury was examined by flow cytometric analysis. Compared with the alkali‑injured normal mice, the alkali‑injured diabetic mice (STZ‑induced) exhibited no significant difference in CrNV occurrence, whereas the laser‑injured diabetic mice exhibited significantly reduced levels of ChNV compared with those of the laser‑injured control animals. The laser‑induced intrachoroidal mRNA expression levels of angiogenic factors, including vascular endothelial growth factor, hypoxia‑induced factor‑1α, chemokine (C‑C motif) ligand 3, and stromal cell‑derived factor‑1α, were reduced in the laser‑injured diabetic mice when compared with laser‑injured control mice. Furthermore, the laser‑induced intrachoroidal infiltration of c‑Kit+ progenitor cells was impaired in the laser‑injured diabetic mice compared with the laser‑injured control mice. Overall, diabetes did not exert a significant effect on the generation of experimental CrNV. However, diabetes reduced laser‑induced ChNV through downregulation of intrachoroidal progenitor cell infiltration and angiogenic factor expression.


Effects of halothane on the pharmacokinetics of lidocaine in digitalis-toxic dogs.
Following the production of digitalis toxicity in dogs as manifested by ventricular tachycardia, the pharmacokinetics of lidocaine treatment of the arrhythmia were determined during pentobarbitone anaesthesia and pentobarbitone-halothane anaesthesia. The elimination rate constants, beta and Ke, and the biological half life T1/2beta were statistically significantly increased during halothane anaesthesia. The volume of distribution was unchanged. The results indicate that the therapeutic loading dose of lidocaine need not be altered during halothane anaesthesia but if a constant infusion is used, the rate of infusion would have to be decreased four fold to avoid toxic plasma levels of lidocaine.


Differential effect of nicotinic acid derivatives on smooth muscle and endothelial cell proliferation.
The pathogenesis of atherosclerosis is a multifactorial process. A possible anti-atherosclerotic drug should therefore interfere with different targets that are important during the development of an atherosclerotic lesion. Two of the early events are the activated migration and proliferation of arterial smooth muscle cells. Here we investigated in several in vivo and in vitro experiments the effect of two nicotinic acid derivatives L44 and L44-0, on smooth muscle cell migration and proliferation. Balloon catheter de-endothelialization was used as an animal model for intimal lesion formation. Migration was subsequently quantified in vitro using the explant outgrowth technique. Subcultured smooth muscle and endothelial cells were used to test the effect of the drugs on proliferation. Time-lapse video microscopy was applied to differentiate between smooth muscle cell migration and proliferation on the level of individual cells. We showed that L44 and L44-0 are very effective in decreasing smooth muscle cell proliferation and migration. Endothelial cell proliferation, important to re-establish endothelial integrity was, however, not affected.


Economic model of bovine fasciolosis in Nigeria: an update.
Bovine fasciolosis is a zoonotic infection transmitted by infected freshwater snail-Lymnaea (Radix) natalensis-in tropical regions. The prevalence of bovine fasciolosis in Nigeria is overwhelming with huge financial cost. In the chronic form of the disease, hyperplastic cholangitis and calcification of bile ducts occur with severe liver damage. The aim of the study was to estimate annual economic losses of bovine fasciolosis in Nigeria. Disease prevalence was estimated at 18.3% (8.5-30.6), average annual disease incidence is maintained at 2.5%, an estimated mortality rate of 1.5%, a total liver condemnation rate of 11.1% were estimated from affected liver due to fasciolosis, annual slaughter rate of 10.5% and a total cattle population of 20 million. A total of 7.3% livestock owners consider fasciolosis as a threat, while only 4.3% have ever used molluscicide. Treatment cost of controlling fasciolosis is estimated at US$375,000, which puts the total annual loss due to fasciolosis at US$26.02 million. Both direct and indirect sources of production losses have an impact on the livestock industry in Nigeria. Bovine fasciolosis threatens food security in Nigeria; therefore, further awareness among livestock owners is needed on control strategies to improve the income base for small-scale livestock farmers.


Monitoring of schools and colleges of pharmacy based on NAPLEX passage rate.
We have evaluated two approaches of monitoring schools and colleges of pharmacy based on North American Pharmacist Licensure Examination (NAPLEX) passage rates. Historically, the Accreditation Council for Pharmacy Education (ACPE) has cited programs for passage rate ≥2 SD below the national average. Since the National Association of Boards of Pharmacy (NABP) no longer reports scores, this procedure is being reconsidered. Our supposition is that the failure rate of ≥2 SD below the average should be retained, but now be based on the national average passage rate rather than score. Yet, we further suggest this is not sufficient due to major variations in class size. We suggest the establishment of a "maximum acceptable failure count," likely in the range of 20 to 25 failing graduates per class. Analyses of data from 2017 to 2019 indicate that this approach would lead to monitoring approximately 15% of existing programs that graduate approximately 40% of individuals failing NAPLEX vs. monitoring only 5% of programs that graduate approximately 9% of individuals failing NAPLEX. The historical method of monitoring pharmacy programs with NAPLEX passage rates ≥2 SD below the national average is not sufficient, primarily due large variations in class size. Since accreditation standards are currently being revised ("Standards 2025"), this would be an ideal time to update methods for selecting programs that warrant monitoring based on inadequate NAPLEX passage rates. We suggest the concept of "maximum acceptable failure count" should be considered when identifying programs to be cited.


Computed tomography examination of periampullary neoplasms.
The hospital records of 24 patients with periampullary neoplasms were reviewed. The clinical triad of jaundice, pain, and weight loss and the radiographic imaging triad of dilated biliary ducts, dilated pancreatic duct, and periampullary mass should suggest the diagnosis of periampullary neoplasm.


[Morphological studies of endocrine cells of the pancreas in rats after exposure to micro- and hypergravity].
Effects of changed gravity on the function of insulin-producing beta-cells and glucagon-producing alpha-cells in pancreas of rats after the 14-day missions of Cosmos-1887, -2044, and those pre- and postnatal development of which till day 60 proceeded at 2 G in a permanently rotating ground centrifuge were studied with the use of morphological techniques. The comparison of beta- and alpha-cells from pancreas of rats flown in space and subjected to relatively reduced gravity after transition from 2 G to 1 G in the laboratory experiment allow to deduce that the postflight reduced production of insulin by beta-cells and glucagon by alpha-cells has been caused by microgravity, whereas the hindered secretion of hormones is associated with the gravity stress within the first hours after recovery.


Laparoscopic complete mesocolic excision for right colon cancer.
Laparoscopic colectomy for colon cancer has become a standard of care, with a number of publications highlighting its safety, improved postoperative recovery, and excellent oncologic outcomes. Complete mesocolic excision, recently reemphasized, is associated with superior oncologic outcomes, although this has not been discussed for laparoscopic surgery. A laparoscopic approach was performed for right colon cancer using a four-trocar technique. The key steps demonstrated are identification and high division of the ileocolic pedicle, medial-to-lateral mobilization of the ascending colon preserving the posterior mesocolic fascia, identification and high division of the right branch of the middle colic artery, mobilization of the greater omentum and hepatic flexure, completion of lateral mobilization of the ascending colon from the retroperitoneum, and mobilization of the small bowel mesentery up to the duodenum. A prospective series of 52 consecutive patients with right colon cancer underwent laparoscopic complete mesocolic excision with high-vessel ligation. Four of the patients required laparoscopic en bloc extended resections for local invasion. The median operative time was 136 min (interquartile range [IQR], 105-167 min), and the median blood loss was 20 ml (IQR, 10-45 ml). The median hospital stay was 3 days (IQR, 3-5 days). All the patients had an R0 oncologic resection with median margins of 12 cm, and a median of 22 lymph nodes (IQR, 18-29 lymph nodes) was retrieved. The median follow-up period was 38 months (IQR, 23-54 months). Of 14 patients with tumor-positive lymph nodes, 2 experienced distant recurrence. There were no local recurrences, but four patients experienced metastatic disease at a median of 37 months (IQR, 22-46 months). The median overall survival time was 38 months (IQR, 23-54 months). The embedded didactic video demonstrates a straight laparoscopic complete mesocolic excision with high-vessel ligation for a patient who had a right colon cancer. Laparoscopic right complete mesocolic excision is a safe and effective procedure associated with excellent 3-year oncologic outcomes and accelerated postoperative recovery.


Protective effects of Vitamin E on endocrine disruptors, PCB-induced dopaminergic neurotoxicity.
The protective effect of an antioxidant, Vitamin E (dl-alpha-tocopherol, 100 mg/kg/day, 8 days p.o. in vivo and 10 and 50 microM in vitro) was tested against PCB-induced neurotoxicity. Microdialysis was used to investigate changes in the striatal extracellular dopamine level and in p-nNOS expression in PCB-treated (Aroclor 1254, 10 microg/ml, 2 microl/min, 5 h; 6 microg was infused by microdialysis probe) rats. Cell viability and levels of p-nNOS expression were observed in PCB-treated (Aroclor 1254, 5 microg/ml) immortalized dopaminergic cell line (CATH.a cells). Treatment with PCB: (1) decreased the extracellular dopamine level in rat striatum, (2) increased p-nNOS expression both in rat striatal tissue and in CATH.a cells, (3) reduced the cell viability of, and (4) increased LDH release by CATH.a cells. However, Vitamin E showed a protective effect against PCB-induced toxicity and downregulation of the extracellular dopamine level. These results indicate that Vitamin E may have neuroprotective effects by inhibiting PCB-induced nNOS phosphorylation.


Failure of tibial polyethylene insert locking mechanism in posterior stabilized arthroplasty.
Tibial insert locking mechanisms are intended to limit interface motion and to prevent backside wear in contemporary modular knee designs. The author describes a case of failure of the polyethylene insert locking mechanism in one design of primary total knee arthroplasty. Loosening of the locking clip was observed within 6 weeks of the index operation without any trauma. The possible mechanism of disengagement is discussed. This rare cause for knee failure has to be recognized because it leads to early revision.


Outcomes of pediatric trauma patients transported from rural and urban scenes.
Mortality differences exist between victims of urban and rural trauma. It is unknown if these differences persist in those patients who survive to HEMS transport. This study examined the in-hospital mortality, hospital LOS, and discharge status of pediatric blunt trauma victims transported by HEMS from rural and urban scenes. Retrospective review of pediatric (< 17) transports between 1997 and 2001. 130 rural and 419 urban pediatric patients transported to area trauma centers were identified from HEMS and registry records. Total mileage, flight times, and scene times were significantly longer for rural flights (P < 0.05). There were no significant differences between the groups with regard to age, gender, vitals, hospital/ICU days, and mortality. After controlling for ISS and mechanism of injury, urban patients were 9 times more likely to die compared to rural patients. Pediatric patients injured in urban areas had shorter total flight and scene times than pediatric patients flown from rural scenes. Higher adjusted in-hospital mortality rates in the urban group were likely a result of faster EMS response and transport times, which minimized out-of-hospital deaths. Factors prior to HEMS arrival may have more impact on the increased mortality rates of rural blunt trauma victims documented nationally.


Increased GABAergic Efficacy of Central Amygdala Projections to Neuropeptide S Neurons in the Brainstem During Fear Memory Retrieval.
The canonical view on the central amygdala has evolved from a simple output station towards a highly organized microcircuitry, in which types of GABAergic neurons in centrolateral (CeL) and centromedial (CeM) subnuclei regulate fear expression and generalization. How these specific neuronal populations are connected to extra-amygdaloid target regions remains largely unknown. Here we show in mice that a subpopulation of GABAergic CeL and CeM neurons projects monosynaptically to brainstem neurons expressing neuropeptide S (NPS). The CeL neurons are PKCδ-negative and are activated during conditioned fear. During fear memory retrieval, the efficacy of this GABAergic influence on NPS neurons is enhanced. Moreover, a large proportion of these neurons (~50%) contain prodynorphin and somatostatin, two neuropeptides inhibiting NPS neurons. We conclude that CeL and CeM neurons inhibit NPS neurons in the brainstem by GABA release and that efficacy of this connection is strengthened upon fear memory retrieval. Thereby, this pathway provides a possible feedback mechanism between amygdala and brainstem routes involved in fear and stress coping.


Professional and patient attitudes to using mobile phone technology to monitor asthma: questionnaire survey.
There is increasing international interest in using emerging technologies to enhance chronic disease management. We aimed to explore the attitudes of patients and primary care professionals to using mobile technology in order to monitor asthma. A piloted questionnaire containing closed and open-ended questions assessing attitudes to using electronic self-monitoring was posted to a random sample of general practitioners, asthma nurses, and people with asthma (12 years and over) in Lothian and Kent, UK, with 2 reminders. In addition to descriptive statistics, patient and clinician responses were compared using Chi-squared or independent sample t-tests. Free-text responses were analysed thematically. Responses were obtained from 130/300 professionals (43%) and 202/389 patients (52%). Patients rated the technology positively and considered that it may help clinicians to provide care, especially during acute attacks. Although rated similarly, professionals were more sceptical about benefits. Both professionals and patients had concerns about the time and cost implications. Of the respondents, 28 professionals (10%) and 62 patients (16%) returned uncompleted questionnaires citing lack of perceived relevance. The low completion rate probably reflects the current status of mobile phone-facilitated care as a minority interest for 'early adopters' of technology. Even for the enthusiastic minority, using mobile phone technology raised questions of clinical benefit, impact on self-management, and concerns about workload and cost, which will need to be addressed prior to wider acceptance.


Deficient astrocyte metabolism impairs glutamine synthesis and neurotransmitter homeostasis in a mouse model of Alzheimer's disease.
Alzheimer's disease (AD) leads to cerebral accumulation of insoluble amyloid-β plaques causing synaptic dysfunction and neuronal death. Neurons rely on astrocyte-derived glutamine for replenishment of the amino acid neurotransmitter pools. Perturbations of astrocyte glutamine synthesis have been described in AD, but whether this functionally affects neuronal neurotransmitter synthesis is not known. Since the synthesis and recycling of neurotransmitter glutamate and GABA are intimately coupled to cellular metabolism, the aim of this study was to provide a functional investigation of neuronal and astrocytic energy and neurotransmitter metabolism in AD. To achieve this, we incubated acutely isolated cerebral cortical and hippocampal slices from 8-month-old female 5xFAD mice, in the presence of 13C isotopically enriched substrates, with subsequent gas chromatography-mass spectrometry (GC-MS) analysis. A prominent neuronal hypometabolism of [U-13C]glucose was observed in the hippocampal slices of the 5xFAD mice. Investigating astrocyte metabolism, using [1,2-13C]acetate, revealed a marked reduction in glutamine synthesis, which directly hampered neuronal synthesis of GABA. This was supported by an increased metabolism of exogenously supplied [U-13C]glutamine, suggesting a neuronal metabolic compensation of the reduced astrocytic glutamine supply. In contrast, astrocytic metabolism of [U-13C]GABA was reduced, whereas [U-13C]glutamate metabolism was unaffected. Finally, astrocyte de novo synthesis of glutamate and glutamine was hampered, whereas the enzymatic capacity of glutamine synthetase for ammonia fixation was maintained. Collectively, we demonstrate that deficient astrocyte metabolism leads to reduced glutamine synthesis, directly impairing neuronal GABA synthesis in the 5xFAD brain. These findings suggest that astrocyte metabolic dysfunction may be fundamental for the imbalances of synaptic excitation and inhibition in the AD brain.


Attachment avoidance predicts inflammatory responses to marital conflict.
Marital stress has been associated with immune dysregulation, including increased production of interleukin-6 (IL-6). Attachment style, one's expectations about the availability and responsiveness of others in intimate relationships, appears to influence physiological stress reactivity and thus could influence inflammatory responses to marital conflict. Thirty-five couples were invited for two 24-h admissions to a hospital research unit. The first visit included a structured social support interaction, while the second visit comprised the discussion of a marital disagreement. A mixed effect within-subject repeated measure model indicated that attachment avoidance significantly influenced IL-6 production during the conflict visit but not during the social support visit. Individuals with higher attachment avoidance had on average an 11% increase in total IL-6 production during the conflict visit as compared to the social support visit, while individuals with lower attachment avoidance had, on average, a 6% decrease in IL-6 production during the conflict visit as compared to the social support visit. Furthermore, greater attachment avoidance was associated with a higher frequency of negative behaviors and a lower frequency of positive behaviors during the marital interaction, providing a mechanism by which attachment avoidance may influence inflammatory responses to marital conflict. In sum, these results suggest that attachment avoidance modulates marital behavior and stress-induced immune dysregulation.


Exercise-based pulmonary rehabilitation for a post-COVID-19 pulmonary fibrosis patient: A case report.
Pulmonary fibrosis is an infamous sequela of coronavirus disease 2019 (COVID-19) pneumonia leading to long-lasting respiratory problems and activity limitations. Pulmonary rehabilitation is beneficial to improve the symptoms of lung fibrosis. We experienced a post-COVID-19 pulmonary fibrosis patient who received a structured exercise-based pulmonary rehabilitation program. This article presents a case of successful pulmonary rehabilitation of a patient with post-COVID-19 pulmonary fibrosis. The patient could not cut off the oxygen supplement even after a successful recovery from COVID-19. Diagnosis of COVID-19 was based on the reverse transcription-polymerase chain reaction (RT-PCR). Pulmonary fibrosis was diagnosed by patient's complaint, clinical appearance, and computed tomography (CT) on chest. The patient underwent ten sessions of exercise-based rehabilitation program according to Consensus Document on Pulmonary Rehabilitation in Korea, 2015. On the 8th day, he could cut off the oxygen supplementation and complete the one-hour exercise without oxygen. He was discharged after completing the 10-session program without any activity limitations. Exercise-based pulmonary rehabilitation will help the post-COVID-19 pulmonary fibrosis patients. This case suggested the importance of pulmonary rehabilitation program to the post-COVID-19 pulmonary fibrosis patient.


Histone Demethylases as Counterbalance to H3K27me3 Silencing in Plants.
The universal importance of epigenetic regulation has become explicit over the last decade. There is now a detailed understanding of the molecular signatures and chromatin-modifying enzymes determining epigenetic regulation. For example, the trimethylation of lysine 27 at histone H3 by Polycomb complexes is a hallmark of silenced gene expression conserved across animal and plant kingdoms. The repressive activity of Polycomb complexes is balanced by the histone demethylase activity of Jumonji C-domain proteins. There has been a lot of research on Polycomb functions and H3K27 methylation; however, until recently, little was known about the role of histone H3K27 demethylases. Here, we review the role of Jumonji C-domain proteins from the plant development perspective. We will recall the history of histone lysine demethylation and explore the recent advances on the H3K27 demethylases in plant biology. Conserved and novel genomic functions of these epigenetic regulators will be discussed.


Exposure to perfluoroalkyl substances in waste recycling workers: Distributions in paired human serum and urine.
Occupational exposure to per- and polyfluoroalkyl substances (PFASs) is an emerging public health concern, because of their potential adverse health effects. In this study, concentrations of 21 legacy and alternative PFASs in paired serum and urine samples collected from 163 workers (from five waste recycling plants) were analyzed. The results showed that the average concentration of 21 PFASs in urine samples (66.6 ng mL-1) were higher than in serum (31.3 ng mL-1). Concentrations of perfluorocarboxylates (PFCAs) in urine were also considerably higher than perfluorosulfonates (PFSAs), especially for short-chain PFCAs. Demographic factors (such as sex, age, working age, and job assignment) on PFAS exposure were also assessed based on the obtained results. PFAS concentrations in serum samples from males were significantly higher than in females, and working age was positively (p < 0.05) associated with most PFAS serum levels. Higher levels of PFAS were found in sorters than in workers with other job assignments, such as managers, suggesting that sorters may be directly exposed to PFASs. Interestingly, perfluorophosphonates (PFPAs) were first to be detected in human urine with >80% detection frequency. The average level of three PFPAs in the serum (7.58 ng mL-1) and urine (1.45 ng mL-1) samples appeared to be higher in comparison with most PFCAs and PFSAs. Thus, the toxicity of PFPAs in human beings needs to be further studied.


Childhood-onset mild cutaneous porphyria with compound heterozygotic mutations in the uroporphyrinogen decarboxylase gene.
Three children (two boys and one girl) from the same family presented with photosensitivity, hyperpigmentation, hypertrichosis, mild skin fragility, blistering and scarring in childhood. On examination, the cutaneous lesions were found to have improved since their previous examinations. Laboratory tests showed raised plasma and urine carboxyporphyrins and decreased uroporphyrinogen decarboxylase enzyme activity in red blood cells. Triggering factors for porphyria were not detected except for a hepatitis C virus infection in the younger boy. The girl's clinical symptoms recurred in late adolescence, after iron and oestrogen treatments. Mutation analysis of the UROD gene detected two missense mutations, 19 A-->G M1V (novel) and 703C-->T P235S (previously reported), in an uncommon compound heterozygous manner in the three siblings.


Skeletal muscle metabolic characteristics before and after energy restriction in human obesity: fibre type, enzymatic beta-oxidative capacity and fatty acid-binding protein content.
Skeletal muscle has the ability to adapt as result of dietary, hormonal or pharmacological interventions affecting energy metabolism. The aim of the present study was to investigate the effects of energy restriction on skeletal muscle metabolic characteristics in obese women. The effects of 8 weeks' energy restriction on body composition, energy expenditure and skeletal muscle characteristics were investigated in 28 healthy obese women. Subjects were aged 37.9 +/- 1.5 years and had a body mass index of 32.0 +/- 0.8 kg m-2. Energy restriction (2800 kJ day-1) resulted in a 10.8 +/- 0.5 kg weight loss consisting of 8. 6 +/- 0.5 kg of fat mass and 2.2 +/- 0.3 kg of fat-free mass. Basal respiratory exchange ratio, sleeping metabolic rate and exercise-induced thermogenesis significantly declined in response to the diet. These changes were accompanied by an increase (P = 0.038) in the skeletal muscle content of cytosolic fatty acid-binding protein (H-FABP), whereas no changes occurred in fibre type distribution or activities of enzymes reflecting beta-oxidation and mitochondrial density (3-hydroxyacyl-CoA dehydrogenase and citrate synthase respectively). The results suggest that increased capacity of intracellular fatty acid transport in skeletal muscle cells is involved in the physiological adaptations of fat metabolism to energy restriction in obese female subjects.


Finger injuries by eyebrow razor blades in infants.
Infants are occasionally injured while playing with their mother's eyebrow razor, and we have treated several infants with flexor tendon injuries, which in some cases were accompanied by damage to the corresponding digital nerves and/or vessels. Here, we report the outcomes in a retrospective case series, with a review of literature. Between January 2013 and October 2019, 8 patients who met our inclusion criteria were initially investigated. The inclusion criteria were: (1) injured by an eyebrow razor during fiddling or grasping, and (2) the availability of complete medical records and radiological data, with follow-up of at least 2 years. The core sutures were performed using a modified Becker (4-strand) method for flexor digitorum profundus (FDP). Nerves and/or vessels were repaired under microscopy. A long-arm mitten cast was then applied, with the fingers slightly flexed in a resting position, for 3 weeks. Then, the children were allowed to return to unrestricted activity. Formal outpatient hand therapy was not performed. Mean postnatal age was 6.3 months. The FDP was injured in zones 1 and 2 in 3 and 5 infants, respectively. Most of the infants were injured near a dressing table, in the bedroom used by their mother. The colors of these razors were all bright, except for one achromatic (white) razor. All of the razors had been left uncovered, without their cap, or were left open in the case of hinged razors. At a mean follow-up of 35.8 months, range of motion was evaluated by the Strickland and modified Strickland methods; all results were "excellent". We encountered no significant complications in any digit: neuroma, tendon retear, stiffness or necrosis. Uncapped or unfolded colorful eyebrow razors pose a high risk of tendon section with concurrent neurovascular injury in infants. Although satisfactory outcomes can be expected, it seems important to prevent the injury through fastidious parental care and changing razor design and color. LEVEL OF EVIDENCE: Level IV, retrospective case series.


PI3K inhibitors changed the p53-induced response of Saos-2 cells from growth arrest to apoptosis.
p53 is activated by stress leading to oncogenic alteration, which induces either cell cycle arrest or apoptosis, although the mechanism involved in this decision has not been fully clarified as yet. This work was undertaken to change the cellular response by inducing apoptosis with PI3K inhibitors to Saos-2 cells that had been growth-arrested in both G1 and G2/M by the wild-type activity of temperature-sensitive (ts) p53. We found that the PI3K/Akt inhibitors LY294002 and wortmannin, but not the MEK inhibitor U0126, were capable of inducing apoptosis in growth-arrested Saos-2 cells, as assessed by an increase in the sub-G1 population, pyknotic nuclei, and DNA ladder formation. We detected the cleavage of caspases 9 and 3, and PARP after LY294002 addition, accompanied by a loss of cytochrome c from the mitochondria, and observed Bax translocation to the mitochondria and down-regulation of phospho-Akt, suggesting that blocking of survival signals triggered the apoptotic signal through the mitochondrial apoptotic pathway. It is thus suggested that the PI3K/Akt pathway played an important role in determining cell fate between growth arrest and apoptosis.


Meta-analysis of three randomized trials of capecitabine plus cisplatin (XP) versus S-1 plus cisplatin (SP) as first-line treatment for advanced gastric cancer.
S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) are standard first-line regimens for advanced gastric cancer (AGC) worldwide. We conducted a meta-analysis using individual participant data (IPD) to investigate which is more suitable. IPD from three randomized trials were collected. In these trials, patients with AGC were randomly allocated to SP (S-1 80-120 mg for 21 days plus cisplatin 60 mg/m2 (q5w)) or XP (capecitabine 2000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w)). In 211 eligible patients, median overall survival (OS) for SP versus XP was 13.5 and 11.7 months (hazard ratio [HR], 0.787; p = 0.114), progression-free survival (PFS) was 6.2 and 5.1 months (HR, 0.767; P = 0.076), and TTF was 5.1 and 4.0 months (HR, 0.611; P = 0.001). The most common grade ≥ 3 adverse events with SP or XP were neutropenia (18% vs. 29%) and anorexia (16% vs.18%). Subgroup analysis demonstrated significant interaction between treatment effect and performance status > 1 (HR, 0.685; P = 0.036), measurable lesion (HR, 0.709; P = 0.049), primary upper third tumor (HR, 0.539; P = 0.040), and differentiated type (HR, 0.549; interaction, 0.236; P = 0.019). For the differentiated type, OS was significantly longer in the SP group (13.2 months) than in the XP group (11.1 months) (HR, 0.549; P = 0.019). For the undifferentiated type, OS was similar in the SP group (14.2 months) and in the XP group (12.4 months) (HR, 0.868; P = 0.476). SP and XP were both effective and well tolerated. SP might be suitable for the pathological differentiated subtype of AGC. The HERBIS-2, HERBIS-4A, and XParTS II trials were registered with UMIN-CTR as UMIN000006105, UMIN000006755, and UMIN000006045, respectively.


Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis.
Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. In eight healthy male smokers and eight ex-smokers, the cutaneous and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine, smoking of one cigarette, arterial occlusion, and reperfusion. Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P < 0.01), whereas QBF was 21.7 +/- 8.6 and 22.7 +/- 9.6 Arbitrary Units (AU), respectively (P = 0.21). TO(2) increased from 49.3 +/- 12.0 to 53.9 +/- 12.0 mm Hg (P = 0.01). Tgluc and Tlact remained unaffected. Smoking decreased SqBF from 4.2 +/- 2.0 to 2.7 +/- 1.2 mL/100 g tissue/min (P < 0.01). QBF decreased from 23.4 +/- 9.2 to 20.3 +/- 7.4 AU (P < 0.01), and TO(2) decreased from 53.9 +/- 12.0 to 48.4 +/- 11.1 mm Hg (P < 0.01). Following smoking, Tgluc decreased from 0.7 +/- 0.1 to 0.6 +/- 0.1 ng/mL (P < 0.01), and Tlact increased from 0.2 +/- 0.1 to 0.3 +/- 0.2 ng/mL (P < 0.01). The observed alterations were similar in smokers and ex-smokers. Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status.


Automated image analysis to improve bead ingestion toxicity test counts in the protozoan Tetrahymena pyriformis.
To improve bead ingestion counts in Tetrahymena pyriformis by automated image analysis as an alternative to direct-counts. Fluorescent latex beads were added to T. pyriformis cultures for ingestion tests. The number of beads ingested by 25 cells was counted directly by epifluorescence microscopy and compared with similar data from image analysis. anova indicated that counts were not significantly different (P < 0.05). The image analysis particularly provided advantages in terms of speed. The image analysis is superior to direct beads counting in T. pyriformis particularly in terms of speed of analysis. The image analysis method is very rapid and will allow many more toxicological analyses to be undertaken with less operator error.


The influence of soil drought and partial waterlogging on water relations of Gmelina arborea seedlings.
Stomatal conductance of unstrossed, soil drought, and previously drought (predrought) Gmelina arborea seedlings increased in the morning and decreased before or immediately after midday. In the unstressed and predrought seedlings, leaf water potential decreased with increases in transpiration. In soil drought seedlings, there was some evidence of decreased hydraulic conductivity from soil to the plant, as indicated by the shape in the slope of the water potential/transpiration relationship. Root growth of drought plants was greater than in their unstressed counterparts at the lowest soil segment of a pot. The partial recovery of predrought seedlings was attributed to this subtantial root growth in the lowest soil segment.In the second experiment, Gmelina arborea seedlings were partially waterlogged, by flooding the polyethylene bag to half its length, for a period of 23 days. Waterlogging induced stomatal closure and reduction in leaf water potential but there was some evidence of tolerance to waterlogging towards the end of treatment. Root growth, shoot and root dry weights were slightly reduced below those of controls. After 9 days of waterlogging, adventitious roots began to form which correlated with depletion of soluble sugars in the shoot but with an increase in the roots.It is suggested that the tolerance of Gmelina plants to either soil drought or waterlogging may partly be due to partitioning of the soluble sugars from shoot to roots for production of roots and formation of adventitious roots respectively which are likely to enhance the flow of water from the soils to the plant. Therefore the plant response is very similar under conditions of increased deficits and surplus of soil water.


Correction: Adipose Tissue-Derived Mesenchymal Stem Cells in Long-Term Dialysis Patients Display Downregulation of PCAF Expression and Poor Angiogenesis Activation.
[This corrects the article DOI: 10.1371/journal.pone.0102311.].


Dynamics of Leishmania chagasi infection in small mammals of the undisturbed and degraded tropical dry forests of northern Colombia.
The infection rate with Leishmania chagasi and the population dynamics of small mammals were studied in an undisturbed forest reserve (Colosó) and an area of highly degraded forest (San Andrés de Sotavento [SAS]) in northern Colombia, both endemic for visceral leishmaniasis. Live trapping of mammals was done every month, and species, age, sex and reproductive status determined. L. chagasi was detected in samples of skin or spleen by the polymerase chain reaction, after extraction of deoxyribonucleic acid using specific primers (DB8/AJS3), and dot blood hybridization. Didelphis marsupialis was found to be infected in Colosó (3/21, 14.3%) and SAS (13/137, 9.5%); its relative abundance was higher in SAS (93/113, 82% of the captures). Although Proechimys canicollis was also found to be infected in Colosó (3/34, 8.8%) and SAS (2/4), its relative abundance was much lower (4%) in SAS than in Colosó (56% of 77 animals captured). Sciurus granatensis, Marmosa robinsoni, Heteromys anomalus, Zygodontomys brevicauda and Metachirus nudicaudatus were less common, and no L. chagasi infection was detected in them.


Adenosine and bone metabolism.
Bone is a dynamic organ that undergoes continuous remodeling while maintaining a balance between bone formation and resorption. Osteoblasts, which synthesize and mineralize new bone, and osteoclasts, the cells that resorb bone, act in concert to maintain bone homeostasis. In recent years, there has been increasing appreciation of purinergic regulation of bone metabolism. Adenosine, released locally, mediates its physiologic and pharmacologic actions via interactions with G protein-coupled receptors, and recent work has indicated that these receptors are involved in the regulation of osteoclast differentiation and function, as well as in osteoblast differentiation and bone formation. Moreover, adenosine receptors also regulate chondrocyte and cartilage homeostasis. These recent findings underscore the potential therapeutic importance of adenosine receptors in regulating bone physiology and pathology.


An unexpected plasma cholinesterase activity rebound after challenge with a high dose of the nerve agent VX.
Organophosphorus chemical warfare agents (nerve agents) are to be feared in military operations as well as in terrorist attacks. Among them, VX (O-ethyl-S-[2-(diisopropylamino)ethyl] methylphosphonothioate) is a low volatility liquid that represents a percutaneous as well as an inhalation hazard if aerosolized. It is a potent irreversible cholinesterase (ChE) inhibitor that causes severe signs and symptoms, including respiratory dysfunction that stems from different mechanisms. VX-induced pulmonary oedema was previously reported in dogs but mechanisms involved are not well understood, and its clinical significance remains to be assessed. An experimental model was thus developed to study VX-induced cardiovascular changes and pulmonary oedema in isoflurane-anaesthetized swine. In the course of this study, we observed a fast and unexpected rebound of plasma ChE activity following inhibition provoked by the intravenous injection of 6 and 12 microg kg(-1) of VX. In whole blood ChE activity, the rebound could stay unnoticed. Further investigations showed that the rebound of plasma esterase activity was neither related to spontaneous reactivation of ChE nor to VX-induced increase in paraoxonase/carboxylesterase activities. A bias in Ellman assay, haemoconcentration or severe liver cytolysis were also ruled out. All in all, these results suggest that the rebound was likely due to the release of butyrylcholinesterase into the blood stream from ChE producing organs. Nature of the organ(s) and mechanisms involved in enzyme release will need further investigations as it may represent a mechanism of defence, i.e. VX scavenging, that could advantageously be exploited.


The anxiety-specific hippocampus-prefrontal cortex pathways links to procrastination through self-control.
Procrastination, which is defined as delaying an intended course of action despite negative outcomes, is demonstrated to have a deal with negative emotion including trait anxiety. Although highly anxious individuals showed impoverished control ability, no studies have indicated the role of self-control in the relationship between trait anxiety and procrastination, and its neural correlates. To this end, we used the sliding window method to calculate the temporal deviation of dynamic functional connectivity (FC) in 312 healthy participants who underwent the resting-state functional magnetic resonance imaging (fMRI) scanning. In line with our hypothesis, higher trait anxiety is linked to more procrastination via poorer self-control. Besides, the dynamic FC analyses showed that trait anxiety was positively correlated with dynamic FC variability in hippocampus-prefrontal cortex (HPC-PFC) pathways, including left rostral hippocampus-left superior frontal gyrus (left rHPC-left SFG), and left rHPC-right middle frontal gyrus (left rHPC--MFG). Furthermore, the structural equation modeling (SEM) uncovered a mediated role of self-control in the association between the anxiety-specific brain connectivity and procrastination. These findings suggest that the HPC-PFC pathways may reflect impoverished regulatory ability over the negative thoughts for anxious individuals, and thereby incurs more procrastination, which enhances our understanding of how trait anxiety links to procrastination.


The effect of the application of cold on hematoma, ecchymosis, and pain at the catheter site in patients undergoing percutaneous coronary intervention.
This study was conducted to determine the effect of the application of cold on hematoma, ecchymosis, and pain in patients undergoing percutaneous coronary intervention. It is a quasi-experimental study with a control group. A total of 200 patients (100 in the control group and 100 in the experimental group) were included in the research. In the experimental group, a cold pack was applied to the bottom of the sandbag for the first 15 min after withdrawing the femoral arterial catheter. Both groups were assessed and followed up at the first 15th minute and 4th, 48th and 72 nd h. After the femoral arterial catheter was withdrawn, ecchymosis and hematoma were smaller and pain was less in the experimental group at the catheter entry site compared to the control group, and the difference was statistically significant (P < 0.01). It was determined that the application of cold reduced the formation of hematomas, ecchymoses and pain in patients after the withdrawal of the femoral arterial catheter.


The genome of human papovavirus BKV.
The complete DNA sequence of human papovavirus BKV(Dun), consisting of 5153 nucleotide pairs, is presented. We describe the segments of the genome which correspond to the replication origin, the tandem repeated sequences, the 5' and 3' ends of the mRNAs, the splice sites, the early and late viral proteins and the putative viral polypeptides. These BKV DNA sequences are compared with analogous regions in the SV40 and Py virus genomes in an attempt to localize viral functions for lytic growth and transformation.


Thin-layer chromatography separation of enantiomers of verapamil using macrocyclic antibiotic as a chiral selector.
Silica gel thin-layer chromatography plates impregnated with macrocyclic antibiotic, vancomycin, as chiral selector were prepared and used for the resolution of (+/-)-verapamil. A mobile phase system of acetonitrile-methanol-water (15:2.5:2.5, v/v) was worked out systematically. The effects of chiral selector, temperature and pH on resolution were also studied. The spots were detected with iodine vapors and the detection limit was found to be 0.074 microg of each enantiomers.


Gadolinium-DTPA enhanced MR imaging of intramuscular abscesses.
Sterile, chemical and bacterial abscesses were induced in the paraspinal muscles of 16 rats before obtaining magnetic resonance (MR) images using a 0.35-T resistive system. Abscess intensity, T1 and T2 values were recorded before and after the intravenous administration of Gd-DTPA (0.2 mmol/kg). The MR appearances of the abscesses were correlated with histologic sections. Both sterile and bacterial abscess were detected on MR images without the use of contrast medium, particularly on the T2-weighted spin echo sequence (TE/TR 56/2000 ms). However, the inflammatory zones of abscesses markedly enhanced in intensity with a corresponding decrease in T1 values after the administration of Gd-DTPA (TE/TR 28/500 ms). A clear distinction between the necrotic center and the cellular periphery of each abscesses was evident only after contrast enhancement (TE/TR 28/500 ms). Thus paramagnetic Gadolinium-DTPA was beneficial for defining the histologic components of abscesses on spin echo MR images.


A new in vitro fertilization technique: intravaginal culture.
Intravaginal culture (IVC) is a new technique elaborated by the authors for the fertilization and culture of human oocytes. Its principle consists of fertilization and early development of the eggs in a closed, air-free milieu without the addition of CO2. One to five ovocytes are deposited in a tube completely filled with 3 ml of culture medium less than 1 hour after their recovery, with 10,000 to 20,000 spermatozoa per ml previously prepared. The tube is then hermetically closed and it is placed in the maternal vagina and held by a diaphragm for incubation for 44 to 50 hours. After this time, the content of the tube is examined and embryos are transferred to the uterus. In the first 100 consecutive punctures, 22 clinical pregnancies were obtained: 17 deliveries, 3 spontaneous abortions, and 2 tubal pregnancies. Also, a randomized study comparing IVC to in vitro fertilization (IVF) was done (160 cycles) and no statistically different cleavage, transfer, or pregnancy rate was seen between IVC and IVF. By simplifying the laboratory manipulations, this technique decreases the cost of IVF and permits its standardization and diffusion. It creates a psychologic comfort permitting active participation of the mother in this stage of embryo development. Also, the use of this technique may give greater knowledge of human gamete metabolism and of the physiology of reproduction.


MR microscopy of hyaline cartilage: current status.
Cartilage degenerative diseases, such as osteoarthritis, affect million of people. Magnetic resonance imaging is presently the most accurate imaging modality in evaluating the state of hyaline cartilage; however, clinical MRI does not accurately reveal early degenerative alterations in cartilage, due mainly to low spatial resolution. Magnetic resonance microscopy (MRM, or microMRI) appears exceptionally well suited to the in vitro or ex vivo study of this heterogeneous tissue, due to its high spatial resolution; however, despite this, further studies are necessary to evaluate the potential of MRM in the detection of early cartilage damage. Herein we briefly review the current applications of MRM in the study of hyaline cartilage. In particular, we review the MR appearance of hyaline cartilage on high-resolution images, the different MRM techniques used to image normal and enzymatically or chemically degraded cartilage and the potential use of contrast agents. The future directions and the relevance of MRM findings for a better understanding of cartilage physiology in health and disease are also discussed.


Structure of the L5 lipopolysaccharide core oligosaccharides of Neisseria meningitidis.
Three different oligosaccharides were isolated by mild acid hydrolysis of the lipopolysaccharides, obtained from Neisseria meningitidis serotype 5, and their structures were elucidated by combined chemical and physical techniques. The use of 500-MHz 1H NMR in both one-dimensional and two-dimensional modes as well as nuclear Overhauser effect experiments were employed. To assist in the structural assignments the purified oligosaccharides were also degraded by chemical and enzymatic procedures to smaller fragments. The largest of the three original oligosaccharides is a triantennary partially O-acetylated decasaccharide in which the largest antenna terminates in a lacto-N-neotetraose unit. The smaller oligosaccharides (heptasaccharide and octasaccharide) except for terminal glycose deletions from the longest antenna are structural replicas of the larger.


Role of nitric oxide in type 1 diabetes-induced osteoporosis.
Type 1 diabetes (T1D)-induced osteoporosis is characterized by decreased bone mineral density, bone quality, rate of bone healing, bone formation, and increased bone resorption. Patients with T1D have a 2-7-fold higher risk of osteoporotic fracture. The mechanisms leading to increased risk of osteoporotic fracture in T1D include insulin deficiency, hyperglycemia, insulin resistance, lower insulin-like growth factor-1, hyperglycemia-induced oxidative stress, and inflammation. In addition, a higher probability of falling, kidney dysfunction, weakened vision, and neuropathy indirectly increase the risk of osteoporotic fracture in T1D patients. Decreased nitric oxide (NO) bioavailability contributes to the pathophysiology of T1D-induced osteoporotic fracture. This review discusses the role of NO in osteoblast-mediated bone formation and osteoclast-mediated bone resorption in T1D. In addition, the mechanisms involved in reduced NO bioavailability and activity in type 1 diabetic bones as well as NO-based therapy for T1D-induced osteoporosis are summarized. Available data indicates that lower NO bioavailability in diabetic bones is due to disruption of phosphatidylinositol 3‑kinase/protein kinase B/endothelial NO synthases and NO/cyclic guanosine monophosphate/protein kinase G signaling pathways. Thus, NO bioavailability may be boosted directly or indirectly by NO donors. As NO donors with NO-like effects in the bone, inorganic nitrate and nitrite can potentially be used as novel therapeutic agents for T1D-induced osteoporosis. Inorganic nitrites and nitrates can decrease the risk for osteoporotic fracture probably directly by decreasing osteoclast activity, decreasing fat accumulation in the marrow cavity, increasing osteoblast activity, and increasing bone perfusion or indirectly, by improving hyperglycemia, insulin resistance, and reducing body weight.


rFSAV promotes Staphylococcus aureus-infected bone defect healing via IL-13- mediated M2 macrophage polarization.
Staphylococcus aureus (S. aureus) contamination commonly occurs in orthopedic internal fixation operations, leading to a delayed healing of the defected bone tissue. However, antibiotic treatments are ineffective in dealing with S. aureus bone infections due to the rise in multiple antimicrobial resistances. Here, we reported the protective effects of a recombinant five-antigen S. aureus vaccine (rFSAV) in an S. aureus infected bone defect model. In this study, we found the number of M2 macrophages markedly increased in the defect site and played a critical role in the healing of defected bone mediated by rFSAV. Mechanistically, rFSAV mediated increased level of IL-13 in bone defect site predominant M2 macrophage polarization. In summary, our study reveals a key role of M2 macrophage polarization in the bone regeneration process in S. aureus infection induced bone defect, which provide a promising application of rFSAV for the treatment of bone infection for orthopedic applications.


Clinical and angiographic risk assessment in patients with left main stem lesions.
Percutaneous coronary intervention of unprotected left main stem lesions has been shown to be a suitable alternative to cardiac surgery in selected patients, emphasizing the need for appropriate risk stratification prior to selection of revascularization modality. Several risk models based on clinical and angiographic variables have been developed to guide patient selection, each of which has significant limitations. This paper reviews contemporary and newly proposed risk models for patients undergoing left main stem revascularization.


Change in the First Cuneiform-Second Metatarsal Distance After Simulated Ligamentous Lisfranc Injury Evaluated by Weightbearing CT Scans.
This study aimed to investigate the widening between the first cuneiform (C1) and second metatarsal (M2) in a Lisfranc ligamentous complex (LLC) joint injury model subjected to successive ligament dissections evaluated by weightbearing computed tomography (CT) scans. Twenty-four intact cadaveric feet served as the control (condition 1). Each component of the LLC (dorsal, interosseous, and plantar ligaments-conditions 2, 3, and 4, respectively) were then sequentially dissected. The specimens were equally randomized to 1 of 3 additional dissections (first or second tarsometatarsal [TMT] joint capsule or first-second intercuneiform ligament [ICL]-conditions 5a, 5b, and 5c, respectively). One additional ligament was then randomly transected (eg, condition 6ac-transection of the first TMT capsule and ICL). Finally, the remaining ligament was transected (condition 7). After each dissection, CT scans were acquired under nonweightbearing (NWB, 0 kg), partial-weightbearing (PWB, 40 kg), and full-weightbearing (FWB, 80 kg) conditions. The distance between the lateral border of C1 and the medial border of M2 was assessed to evaluate diastasis. Linear regressions with 95% CIs and converted q values were used to compare the measured data. No significant differences were found within the control. In condition 4, an average axial plane widening relative to control of 1.6 mm (95% CI, 1.5-1.8) and 2.1 mm (95% CI, 1.9-2.2) was observed under PWB and FWB. A coronal plane widening of 1.5 mm (95% CI, 1.3-1.6) and 1.9 mm (95% CI, 1.7-2.1) under PWB and FWB, respectively, was measured. A 95% CI of at least a 2-mm widening during PWB was demonstrated in 5c, 6ac, 6bc, and 7. Weightbearing computed tomography (WBCT) scans were used to detect ligamentous Lisfranc injuries in a cadaveric model. Relative axial widening greater than 1.5 mm under PWB conditions could indicate a complete LLC injury. Complete transection of the intercuneiform 1-2 ligament was required to detect a 2-mm widening in the nonweightbearing condition. This study provides insight on the detection of various severities of LLC injuries using WBCT imaging.


Electrophysiologic properties and antiarrhythmic mechanisms of intravenous N-acetylprocainamide in patients with ventricular dysrhythmias.
To define electrophysiologic properties and antiarrhythmic mechanisms of N-acetylprocainamide (NAPA), we studied 16 patients with symptomatic ventricular dysrhythmias. Electrophysiologic studies were performed before and after intravenous infusion of NAPA at 20 mg/kg over 20 minutes, achieving plasma concentrations of 24 +/- 3.2 to 35.5 +/- 4.5 micrograms/ml. NAPA did not significantly change sinus cycle length or atrioventricular (AV) conduction times (PA, AH, HV, and QRS), but it lengthened the QTc interval (p less than 0.001) during sinus rhythm. Programmed atrial stimulation revealed that NAPA had no discernible effects on AV nodal conduction; however, it exerted depressive effects on the His-Purkinje system in 9 of 16 patients. In 7 of 16 patients who manifested frequent ventricular premature beats (VPBs), NAPA abolished VPBs in only three of them; NAPA induced progressive prolongation of the premature coupling interval before complete abolition of VPBs. In 8 of 16 patients who had inducible repetitive ventricular response (RVR) because of reentry within the His-Purkinje system, NAPA narrowed or abolished the RVR zone in 3 patients and slowed the RVR rate with widening of the RVR zone in the remaining 5 patients. In 2 of 16 patients with slow ventricular tachycardia (VT), NAPA had no antiarrhythmic effects. By contrast, in the other 2 of 16 patients in whom sustained VT could be reproducibly elicited with programmed ventricular stimulation, NAPA slowed the rate of VT and suppressed VT inducibility. We conclude that electrophysiologic properties of NAPA are slightly different from those of procainamide and that NAPA is not uniformly effective for suppressing ventricular dysrhythmias, but its antiarrhythmic mechanisms are similar to those of procainamide.


A computational model of cell membrane bioelectric polarization and depolarization, connected with cell proliferation, in different tissue geometries.
A reliable theory of biological tissues growth and organization, a fundamental tool for a comprehensive interpretation of experimental observations and a guide to progress in life sciences, is definitively missing. This would support the advancement of knowledge for both normal and pathological expansion and regulation of tissues and organisms. In this work is presented a computational model of cell culture that describes its growth and organization using cell proliferation as its default state, constrained by contact inhibition, closely connected to the cell bioelectric state. The model results describe in a correct way the reported experimental results, involving contact inhibition due to the presence of other cells, and gap junctions for signaling, molecules exchange and extracellular environment sensing. Starting from depolarized cells (in this model considered tantamount to proliferative), the cell culture grows until it fills the available domain and, due to the contact inhibition constraint, it turns into quiescence (a consequence of cell polarization), except on the periphery. Using drugs or via protein expression manipulation, it is possible to change the final tissue state, to fully polarized or depolarized. Other experimental tests are proposed and the expected results simulated. This model can be extended to pathological events, such as carcinogenesis, with cells homeostasis perturbed by a cell depolarizing (carcinogenic) event and express its default proliferative state without adequate control. This simplified model of tissue organization, regulated by the cell's bioelectric state and their interaction with vicinity, is an alternative to the description of the experimental results by mechanical stress, and can be further tested and extended in dedicated experiments.


Are postural responses to backward and forward perturbations processed by different neural circuits?
Startle pathways may contribute to rapid accomplishment of postural stability. Here we investigate the possible influence of a startling auditory stimulus (SAS) on postural responses. We formulated four specific questions: (1) can a concurrent SAS shorten the onset of automatic postural responses?; and if so (2) is this effect different for forward versus backward perturbations?; (3) does this effect depend on prior knowledge of the perturbation direction?; and (4) is this effect different for low- and high-magnitude perturbations? Balance was perturbed in 11 healthy participants by a movable platform that suddenly translated forward or backward. Each participant received 160 perturbations, 25% of which were combined with a SAS. We varied the direction and magnitude of the perturbations, as well as the prior knowledge of perturbation direction. Perturbation trials were interspersed with SAS-only trials. The SAS accelerated and strengthened postural responses with clear functional benefits (better balance control), but this was only true for responses that protected against falling backwards (i.e. in tibialis anterior and rectus femoris). These muscles also demonstrated the most common SAS-triggered responses without perturbation. Increasing the perturbation magnitude accelerated postural responses, but again with a larger acceleration for backward perturbations. We conclude that postural responses to backward and forward perturbations may be processed by different neural circuits, with influence of startle pathways on postural responses to backward perturbations. These findings give directions for future studies investigating whether deficits in startle pathways may explain the prominent backward instability seen in patients with Parkinson's disease and progressive supranuclear palsy.


Few-Layered MoS2/Acetylene Black Composite as an Efficient Anode Material for Lithium-Ion Batteries.
Novel MoS2/acetylene black (AB) composite was developed using a single-step hydrothermal method. A systematic characterization revealed a few-layered, ultrathin MoS2 grown on the surface of AB. The inclusion of AB was found to increase the capacity of the composite and achieve discharging capacity of 1813 mAhg-1.