Experimental and Numerical Study of the Thermo-Viscoplastic Behavior of NICRO 12.1 for Perforation Tests.
Dynamic impact tests using thin metal plates for ballistic characterization have received significant attention in recent years. The Johnson-Cook (J-C) model is extensively used in numerical modeling of impact and penetration in metals. The AISI (American Iron and Steel Institute) 301 steel family presents good impact behavior, excellent formability, and high corrosion resistance. Thus, NICRO (Nickel and Hard Chrome Plated Steel) 12.1 (part of the AISI 301 steel family) was chosen in this work, although parameters of the J-C model or impact results were not found in the literature. In this work, NICRO 12.1 steel plates, were characterized in ballistics with an initial impact velocity up to 200 m/s and three shape nose projectiles. The Johnson-Cook parameters for the NICRO 12.1 steel were calculated for a large range of temperatures and strain rates. Impact tests were carried out using three projectiles: conical, hemispherical, and blunt. The ballistic curves, failure mode, and maximum deformation obtained with each projectile, experimentally and numerically, were compared, and a good correlation was obtained.


Inactivation of ceramide transfer protein during pro-apoptotic stress by Golgi disassembly and caspase cleavage.
The mammalian Golgi apparatus is composed of multiple stacks of cisternal membranes organized laterally into a polarized ribbon. Furthermore, trans-Golgi membranes come in close apposition with ER (endoplasmic reticulum) membranes to form ER-trans-Golgi contact sites, which may facilitate transfer of newly synthesized ceramide from the ER to SM (sphingomyelin) synthase at the trans-Golgi via CERT (ceramide transfer protein). CERT interacts with both ER and Golgi membranes, and together with Golgi morphology contributes to efficient SM synthesis. In the present study, we show that Golgi disassembly during pro-apoptotic stress induced by TNFα (tumour necrosis factor α) and anisomycin results in decreased levels of CERT at the Golgi region. This is accompanied by a caspase-dependent loss of full-length CERT and reduction in de novo SM synthesis. In vitro, CERT is cleaved by caspases 2, 3 and 9. Truncated versions of CERT corresponding to fragments generated by caspase 2 cleavage at Asp213 were mislocalized and did not promote efficient de novo SM synthesis. Thus it is likely that during cellular stress, disassembly of Golgi structure together with inactivation of CERT by caspases causes a reduction in ceramide trafficking and SM synthesis, and could contribute to the cellular response to pro-apoptotic stress.


Naturalistic language sampling to characterize the language abilities of 3-year-olds with autism spectrum disorder.
Characterization of language in naturalistic settings in autism spectrum disorder has been lacking, particularly at young ages, but such information is important for parents, teachers, and clinicians to better support language development in real-world settings. Factors contributing to this lack of clarity include conflicting definitions of language abilities, use of non-naturalistic standardized assessments, and restricted samples. The current study examined one of the largest datasets of naturalistic language samples in toddlers with autism spectrum disorder, and language delay and typically developing contrast groups at age 3. A range of indices including length of phrase, grammatical markings, and social use of language was assayed during a naturalistic observation of a parent-child play session. In contrast to historical estimates, results indicated only 3.7% of children with autism spectrum disorder used no words, and 34% were minimally verbal. Children with autism spectrum disorder and language delay exhibited similar usage of grammatical markings, although both were reduced compared to typically developing children. The greatest difference between autism spectrum disorder and language delay groups was the quantity of social language. Overall, findings highlight a range of language deficits in autism spectrum disorder, but also illustrate that the most severe level of impairments is not as common in naturalistic settings as previously estimated by standardized assessments.


Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease.
Brain amyloidosis with abundant beta/A4 protein deposition in plaques and cortical and meningeal vessels is found in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). In contrast to AD, no neuritic pathology or classical congophilic plaques are found in HCHWA-D. Unlike most AD cases, the congophilic angiopathy in HCHWA-D is very severe. It is still unknown whether beta/A4 deposits in plaques and vessels have the same origin. In this study, we have used frozen cortical tissue of HCHWA-D and AD patients to investigate the beta/A4 amyloid protein and the amyloid precursor protein (APP) in different types of plaques and congophilic angiopathy. Immunohistochemical staining was conducted using antibodies against synthetic beta/A4 proteins and antibodies against APP including MAbP2-1, a monoclonal antibody against purified protease nexin-2, which is the secreted form of APP. In contrast to immunohistochemical studies on formalin-fixed, paraffin-embedded tissue, frozen tissue of HCHWA-D patients revealed a very high number of beta/A4 plaques resembling AD. All plaques were of the diffuse type. Double-staining with MabP2-1 and beta/A4 antisera revealed: 1) the presence of APP immunoreactivity in classical plaques and transitional forms; 2) the absence of APP immunoreactivity in diffuse plaques in HCHWA-D and AD; and 3) pronounced APP immunoreactivity in congophilic vessels in HCHWA-D in contrast to weak APP staining in congophilic vessels in AD. Together these findings suggest that: a) the presence of APP in plaques is related to neuritic changes; b) different processes occur in amyloid formation in plaques and vessels; and c) differences exist between the process of amyloid formation in HCHWA-D and AD.


[Application of plasma-mediated cold ablation in otorhinolaryngology].
A total of 226 surgical operations were made with a Coblator II plasma surgery system including tonsillectomy, uvulopalatoplasty, reduction of inferior turbinates, and removal of soft palate neoplasm. This method permitted to avoid intraoperative bleeding and reduce to 2% the frequency of hemorrhage in the postoperative period. Moreover, pain syndrome was virtually absent and reactive processes in soft tissues were rare. Taken together, these effects accounted for the lower rate of postoperative complications, faster patients' recovery, and shorter hospitalization time.


The relationship between anti-factor Xa level and clinical outcome in patients receiving enoxaparine low molecular weight heparin to prevent deep vein thrombosis after hip replacement.
Studies in experimental animals have demonstrated that there is a relationship between levels of low molecular weight (LMW) heparin and both bleeding and inhibition of thrombosis. The relationship between these outcomes and ex vivo anti-factor Xa levels has been examined in 163 patients undergoing total hip replacement who were given prophylaxis once daily with a LMW heparin (enoxaparine). Fifty patients received 60 mg of enoxaparine and 113 received 40 mg, both regimens being administered subcutaneously once daily. Blood samples for anti-factor Xa levels were collected 12 hours after the injection on the day of surgery and on days 1, 3 and 6, postoperatively. The incidence of wound hematoma was 5.3% when the maximum anti-factor Xa level was less than or equal to 0.2 units per ml, but increased to 24.5% when the anti-factor Xa level exceeded 0.2 units per ml, P = 0.0008. The incidence of postoperative thrombosis was low (6.3%) if the minimum anti-factor Xa level exceeded 0.1 units per ml, but increased to 14.6% when less than or equal to 0.1 units per ml, and to 18.8% if the anti-factor Xa level was less than or equal to 0.05 units per ml. Regression analysis revealed that there was a statistically significant relationship between anti-factor Xa level and wound hematoma, P = 0.002 and anti-factor Xa level and thrombosis, P = 0.03. These findings suggest that when enoxaparine is administered as a once daily subcutaneous injection, the 12 hour anti-factor Xa level should not exceed 0.2 units per ml to minimize bleeding and levels greater than 0.05 units per ml should be obtained to optimize efficacy.


The Migraine Aura: A Problem for Vision Theory?
The scintillating zigzag pattern that a migraine patient may see as an illusion before the onset of headache offers a unique investigative approach to visual mechanisms. The likeliest interpretation of these zigzags is that they are the spontaneous discharges of the orientation-selective neurons first described in the striate cortex by Hubel and Wiesel (Hubel DH, Wiesel TN. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J Physiol (Lond). 1962 Jan;160:106-54; and Hubel DH, Wiesel TN. Receptive fields and functional architecture of monkey striate cortex. J Physiol (London). 1968 Mar;195(1):215-43). Although these cells appear to lie in rows in V1, as Hubel and Wiesel found, very few angles in the visual field are represented; this, and the coarseness of the representation, makes it unlikely that the cells act as feature detectors. The orientation-selective cells could, however, monitor the amount of light falling on the retina and thereby enable color constancy to be achieved. The cells may also serve as coarse movement detectors. The new model of cell organization in human V1 enables us to determine the approximate sizes of the receptive fields of the orientation-selective cells.


Chronic Thromboembolic Pulmonary Hypertension and Antiphospholipid Syndrome with Immune Thrombocytopenia: A Case Report.
BACKGROUND Antiphospholipid syndrome is an autoimmune disorder characterized by a hypercoagulable state associated with circulating antiphospholipid antibodies. The presence of antiphospholipid antibodies can result in a variety of clinical symptoms, such as thrombocytopenia, stillbirth, endocardial pathologies, and recurrent pulmonary embolism. CASE REPORT We present the case of a 23-year-old man with antiphospholipid syndrome and chronic thromboembolic pulmonary hypertension who developed severe thrombocytopenia. The patient died from right heart failure before the thrombocytopenia could be managed, preventing performance of a pulmonary endarterectomy procedure. CONCLUSIONS Managing platelet counts in patients with antiphospholipid syndrome prior to major surgery is very problematic, and requires similar treatment strategy as in patients with immune thrombocytic thrombocytopenia. Platelet transfusions may further decrease platelet count, as it can trigger formation of new antibodies.


Association of Maternal Depressive Symptoms and Offspring Physical Health in Low-Income Families.
Objectives The present study sought to examine the association between maternal depressive symptoms and characteristics of offspring physical health, including health status, health behaviors, and healthcare utilization, among low-income families. Maternal engagement was explored as a mediator of observed effects. Methods Cross-sectional survey data from a community sample of 4589 low-income women and their preschool-age children participating in the WIC program in Los Angeles County were analyzed using logistic, Poisson, and zero-inflated negative binomial regression. Mediation was tested via conditional process analyses. Results After controlling for the effects of demographic characteristics including maternal health insurance coverage, employment status, education, and preferred language, children of depressed women (N = 1025) were significantly more likely than children of non-depressed women (N = 3564) to receive a "poor" or "fair" maternal rating of general health (OR 2.34), eat fewer vegetables (IRR: 0.94) more sweets (IRR: 1.20) and sugary drinks daily (IRR: 1.32), and consume fast food more often (OR 1.21). These children were also less likely to have health insurance (OR 1.59) and more likely to receive medical care from a public medical clinic or hospital emergency room (OR 1.30). Reduced maternal engagement partially mediated associations between maternal depressive symptoms and several child health outcomes including poor diet, health insurance coverage, and use of public medical services. Conclusions for Practice Maternal depressive symptoms are associated with poor health among preschool-age children in low-income families. Prevention, screening, and treatment efforts aimed at reducing the prevalence of maternal depression may positively affect young children's health.


Genetic analysis of developmental mechanisms in hydra. V. Cell lineage and development of chimera hydra.
Chimeric hydra were produced by making use of a strain (nf-1) which lacks interstitial cells, nerve cells and nematocytes. This strain arises by spontaneous loss of interstitial cells from its parental strain (sf-1) (Sugiyama & Fujisawa, 1978). Reintroduction of interstitial cells from other strains into nf-1 leads to the creation of chimeric strains that consisted of epithelial cells derived from strain sf-1 and interstitial cells and their derivatives (nerves and nematocytes) from other strains. In chimeras, interstitial or epithelial cells apparently maintain very stable cell lineages; no indication was obtained that suggested interstitial cell differentiation into epithelial cells or dedifferentiation in the opposite direction during the long courses of chimera cultures (up to one year). Developmental characters of chimeras were examined and compared to those of the epithelial cell (sf-1) and the interstitial cell donors. Almost all of the chimera's characters examined (growth rate, budding rate, tentacle numbers, polyp size, regenerative capacity, etc.) closely resembled those of the epithelial cell donor, but not of the interstitial cell donors. This suggests that epithelial cells, rather than interstitial or nerve cells, are the primary determinant of most, if not all, of hydra developmental characters.


Twinned alpha-LiRb2(CF3SO3)3.
The investigated crystal of alpha-LiRb(2)(CF(3)SO(3))(3) [lithium dirubidium tris(trifluoromethanesulfonate)] was a twin, with the twin matrix given by (-100/010/001). The structure consists of channel-like patterns built up of lipophilic CF(3) groups pointing towards each other. The polar interstices are occupied by cations. One Rb atom is coordinated by O atoms in the form of a distorted square antiprism, while the coordination around the second Rb atom is best described as a distorted pentagonal plane, with one O atom and one F atom situated above and an additional F atom below this plane. The O atoms around the Li atom form a strongly distorted tetrahedron.


Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers.
Heme oxygenase-1 (HO-1) is a redox-sensitive inducible protein that provides efficient cytoprotection against oxidative stress. Curcumin, a polyphenolic natural compound that possesses anti-tumor and anti-inflammatory properties, has been reported recently to induce potently HO-1 expression in vascular endothelial cells (Free Rad Biol Med 28:1303-1312, 2000). Here, we extend our previous findings by showing that caffeic acid phenethyl ester (CAPE), another plant-derived phenolic agent, markedly increases heme oxygenase activity and HO-1 protein in astrocytes. The effect seems to be related to the peculiar chemical structures of curcumin and CAPE, because analogous antioxidants containing only portions of these two molecules were totally ineffective. At a final concentration of 30 microM, both curcumin and CAPE maximally up-regulated heme oxygenase activity while promoting marked cytotoxicity at higher concentrations (50-100 microM). Similar results were obtained with Curcumin-95, a mixture of curcuminoids commonly used as a dietary supplement. Incubation of astrocytes with curcumin or CAPE at concentrations that promoted maximal heme oxygenase activity resulted in an early increase in reduced glutathione followed by a significant elevation in oxidized glutathione contents. A curcumin-mediated increase in heme oxygenase activity was not affected by the glutathione precursor and thiol donor N-acetyl-L-cysteine. These data suggest that regulation of HO-1 expression by polyphenolic compounds is evoked by a distinctive mechanism which is not necessarily linked to changes in glutathione but might depend on redox signals sustained by specific and targeted sulfydryl groups. This study identifies a novel class of natural substances that could be used for therapeutic purposes as potent inducers of HO-1 in the protection of tissues against inflammatory and neurodegenerative conditions.


Mortality risk factors during readmission at the Department of Medicine.
Readmission is an indicator of quality of inpatient care. A study from Hong Kong found readmission mortality rate to be 5.1%. There are limited reports on risk factors for mortality other than co-morbid diseases in readmission patients. This study, thus, aims to evaluate risk factors for mortality during readmission. This study was conducted at a university hospital in Thailand. The inclusion criteria were patients aged ≥15 years and readmission to internal medicine wards within 28 days after discharge. The outcome of the study was death during readmission. Risk factors for readmission mortality were analyzed using multivariate logistic regression analysis. There were 10,389 admissions to the Department of Medicine, Khon Kaen University, of which 407 required readmission (3.90%). Of those patients, 75 (18.43%) died during readmission. There were 6 independent factors associated with death in patients who were readmitted, including advanced age (>60 years), presence of more than 2 co-morbid diseases, admission duration of >14 days, fever at previous discharge, low hemoglobin (<12 g/dL), and having undergone over 5 procedures. Older age, co-morbid diseases, readmission duration, presence of low hemoglobin at previous discharge, and numbers of procedures at readmission were significantly associated with increased mortality risk for readmission patients.


A modified Nottingham prognostic index for breast cancer patients diagnosed in Denmark 1978-1994.
Stage of disease at diagnosis is a predictor of breast cancer survival. We used data from the Danish Cancer Register and the Danish Breast Cancer Cooperative Group to study stage distribution in 0-69-year-old Danish breast cancer patients diagnosed in 1978-1994. We constructed a modified Nottingham Prognostic Index (NPI) calculated from the number of excised and positive lymph nodes, malignancy grade and tumour diameter. This NPI could be calculated for 63% of the patients, and among these the stage distribution improved during the study period. The proportion of patients with a poor prognostic score decreased from 27% to 20%. Based on a comparison of the crude 3-year survival of patients with an NPI score and those without, it seems probable that the stage of disease at diagnosis on average improved in Danish breast cancer patients below age 70 during the 1980s and the early 1990s.


Recessive Charcot-Marie-Tooth and multiple sclerosis associated with a variant in MCM3AP.
Variants in MCM3AP, encoding the germinal-centre associated nuclear protein, have been associated with progressive polyneuropathy with or without intellectual disability and ptosis in some cases, and with a complex phenotype with immunodeficiency, skin changes and myelodysplasia. MCM3AP encoded protein functions as an acetyltransferase that acetylates the replication protein, MCM3, and plays a key role in the regulation of DNA replication. In this study, we report a novel variant in MCM3AP (p.Ile954Thr), in a family including three affected individuals with characteristic features of Charcot-Marie-Tooth neuropathy and multiple sclerosis, an inflammatory condition of the central nervous system without known genetic cause. The affected individuals were homozygous for a missense MCM3AP variant, located at the Sac3 domain, which was predicted to affect conserved amino acid likely important for the function of the germinal-centre associated nuclear protein. Our data support further expansion of the clinical spectrum linked to MCM3AP variant and highlight that MCM3AP should be considered in patients with accompaniment of recessive motor axonal Charcot-Marie-Tooth neuropathy and multiple sclerosis.


Vaccine Confidence and Hesitancy at the Start of COVID-19 Vaccine Deployment in the UK: An Embedded Mixed-Methods Study.
Background: Approval for the use of COVID-19 vaccines has been granted in a number of countries but there are concerns that vaccine uptake may be low amongst certain groups. Methods: This study used a mixed methods approach based on online survey and an embedded quantitative/qualitative design to explore perceptions and attitudes that were associated with intention to either accept or refuse offers of vaccination in different demographic groups during the early stages of the UK's mass COVID-19 vaccination programme (December 2020). Analysis used multivariate logistic regression, structural text modeling and anthropological assessments. Results: Of 4,535 respondents, 85% (n = 3,859) were willing to have a COVID-19 vaccine. The rapidity of vaccine development and uncertainties about safety were common reasons for COVID-19 vaccine hesitancy. There was no evidence for the widespread influence of mis-information, although broader vaccine hesitancy was associated with intentions to refuse COVID-19 vaccines (OR 20.60, 95% CI 14.20-30.30, p < 0.001). Low levels of trust in the decision-making (OR 1.63, 95% CI 1.08, 2.48, p = 0.021) and truthfulness (OR 8.76, 95% CI 4.15-19.90, p < 0.001) of the UK government were independently associated with higher odds of refusing COVID-19 vaccines. Compared to political centrists, conservatives and liberals were, respectively, more (OR 2.05, 95%CI 1.51-2.80, p < 0.001) and less (OR 0.30, 95% CI 0.22-0.41, p < 0.001) likely to refuse offered vaccines. Those who were willing to be vaccinated cited both personal and public protection as reasons, with some alluding to having a sense of collective responsibility. Conclusion: Dominant narratives of COVID-19 vaccine hesitancy are misconceived as primarily being driven by misinformation. Key indicators of UK vaccine acceptance include prior behaviors, transparency of the scientific process of vaccine development, mistrust in science and leadership and individual political views. Vaccine programmes should leverage the sense of altruism, citizenship and collective responsibility that motivated many participants to get vaccinated.


Stage-specific skeletal and visceral defects of the I(Kr)-blocker almokalant: further evidence for teratogenicity via a hypoxia-related mechanism.
As a class effect, potent I(Kr)-blockers have been shown to induce stage-specific external malformations. The aim of this study was to investigate whether I(Kr)-blockers also induce stage-specific visceral and skeletal defects and to further elucidate a proposed arrhythmia-hypoxia hypothesis. Single oral doses of the selective I(Kr)-blocker almokalant (ALM) 25-150 micromol/kg, 7-14 dams/group, were given to Sprague-Dawley rats on gestation days (GD) 10-14, and the fetuses were examined for malformations on GD 21. One group was pretreated with the spin-trapping agent, alpha-phenyl-N-t-butylnitrone (PBN), given intraperitoneally 1 hr before ALM on GD 11. Cardiac ventricular septum defects and vascular malformations were observed after dosing on GD 10-11 and, to a lesser degree, on GD 12-13. Urogenital defects, absence/malposition of the postcaval lung lobe, and attenuated diaphragm were observed mainly on GD 10-11. Skeletal examination showed a high incidence of vertebral abnormalities on thoracic level on GD 10, on lower thoracic to caudal level on GD 11, and sternebral defects were observed all days. On GD 13 brachy-, oligo-, and syndactyly of the forepaw were induced, and of the hindpaw on GD 14. PBN reduced the incidence of both visceral and skeletal defects. The stage specificity of observed visceral and skeletal defects correlates well with what has been reported in the literature after temporary interruption of oxygen supply during the same stages of development. The protective effect by PBN present further evidence that the teratogenicity of potent I(Kr)-blockers is related to induction of hypoxia- reoxygenation injury due to embryonic cardiac arrhythmia.


The feasibility of accelerator-based in vivo neutron activation analysis of nitrogen.
The feasibility of accelerator-based in vivo neutron activation analysis of nitrogen has been investigated. It was found that a moderated neutron flux from approximately 10 microA of 2.5 MeV protons on a 9Be target performed as well as, and possibly slightly better than the existing isotope-based approach in terms of net counts per unit subject dose. Such a system may be an attractive alternative to the widespread use of (238,239)Pu/Be or 252Cf neutron sources, since there is more flexibility in the energy spectrum generated by accelerator-based neutron sources. From a radiation safety standpoint, accelerators have the advantage in that they only produce radiation when in operation. Furthermore, an accelerator beam can be pulsed, to reduce background detected in the prompt-gamma measurement, and such a device has a wide range of additional biological and medical applications.


Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia.
We investigated the effects of the direct thrombin inhibitor argatroban, patient demographics, and the platelet count on thrombotic risks in heparin-induced thrombocytopenia (HIT), a serious thrombotic condition, to determine if argatroban provides effective antithrombotic therapy in patients with HIT without increasing bleeding. We retrospectively analyzed thrombotic outcomes in 882 HIT patients (697 patients receiving mean argatroban doses of 1.7 to 2.0 mug/kg/min for 5 to 7 days, plus 185 historical control subjects) from previously reported prospective studies. Time-to-event analyses of our primary end point-a thrombotic composite of death due to thrombosis, amputation secondary to HIT-associated thrombosis, or new thrombosis within 37 days-and the individual components were conducted, with hazard ratios estimated for treatment with and without adjustments for patient age, gender, race, weight, and baseline platelet count. Argatroban, vs control, significantly reduced the thrombotic composite risk (HIT: hazard ratio, 0.33; 95% confidence interval [CI], 0.20 to 0.54, p < 0.001; HIT with thrombosis: hazard ratio, 0.39; 95% CI, 0.25 to 0.62, p < 0.001), regardless of covariate adjustments. More argatroban-treated patients than control subjects remained thrombotic event free during follow-up, regardless of whether baseline thrombosis was absent (91% vs 73%) or present (72% vs 50%). Argatroban significantly reduced new thrombosis (p < 0.001) and death due to thrombosis (p </= 0.001). Major bleeding was similar between groups (6 to 7%, p = 0.74). Thrombotic risks were 2 times greater in nonwhite than in white patients, 1.7 times greater in female than male patients with HIT and thrombosis, and increased with decreasing weight or platelet count. Argatroban, vs control, provides effective antithrombotic therapy in patients with HIT, without increasing bleeding. Patients at higher risk for HIT-associated thrombosis include women, nonwhites, and individuals with current HIT-associated thrombosis, lower body weight, or more severe thrombocytopenia.


The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences.
The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- and/or C-terminal prior glycosylation (GalNAc-O-Ser/Thr) preferences modulated by the lectin domain. Here we report studies on GalNAc-T4 that reveal the origins of its unique N-terminal long-range glycopeptide specificity, which is the opposite of GalNAc-T2. The GalNAc-T4 structure bound to a monoglycopeptide shows that the GalNAc-binding site of its lectin domain is rotated relative to the homologous GalNAc-T2 structure, explaining their different long-range preferences. Kinetics and molecular dynamics simulations on several GalNAc-T2 flexible linker constructs show altered remote prior glycosylation preferences, confirming that the flexible linker dictates the rotation of the lectin domain, thus modulating the GalNAc-Ts' long-range preferences. This work for the first time provides the structural basis for the different remote prior glycosylation preferences of the GalNAc-Ts.


Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates.
Long-acting dopamine agonist drugs induce a lower incidence of dyskinesia in MPTP-treated primates and patients with Parkinson's disease compared to pulsatile treatment with levodopa, supporting the concept of continuous dopaminergic stimulation as a means of dyskinesia avoidance. We examined the effects of L-dopa administered with or without the COMT inhibitor entacapone on dyskinesia induction in previously untreated MPTP-treated common marmosets. Administration of L-dopa (12.5 mg/kg p.o.) plus carbidopa twice daily produced fluctuating improvement in motor behavior coupled with dyskinesia. Coadministration with entacapone produced similar patterns of motor improvement and dyskinesia that were not different from that produced by L-dopa alone. Treatment with L-dopa (6.25 mg/kg p.o.) plus carbidopa four times daily reversed motor disability and induced dyskinesia in a manner that was not different from the twice-daily treatment regimens. However, coadministration with entacapone produced more continuous improvement in locomotor activity with less dyskinesia than animals treated with L-dopa four times daily alone. These data support the notion that pulsatile stimulation contributes to the development of dyskinesia and suggests that more frequent dosing of L-dopa plus entacapone may be a useful treatment strategy for patients in the early stages of Parkinson's disease.


[Extrascleral ballooning. 2. New approaches: double and sector ballooning].
Treatment of retinal detachment with the use of distended balloons (extrascleral ballooning) holds good promise due to ease of operation and low traumatism. Unfortunately it may be used only in cases with fresh not high detachments of the retina with solitary or multiple ruptures up to 1-2 optic disk diameters in length. That is why the authors suggest two new modifications of the method: double and sector ballooning, widening the indications for the employment of the method. Double ballooning is recommended for cases with retinal detachments with 2 ruptures up to 2 disc diameters in length, located at a distance of 2-3 disc diameters from each other within one quadrant or in different quadrants of the fundus oculi. Sector ballooning is recommended for cases with retinal detachments with ruptures or breaks off 3-6 disc diameters in length. The results of 24 surgeries are analyzed. Double ballooning is effective in 77 percent of cases, sector ballooning in 82 percent. The presence of proliferative vitreoretinopathy, stages C3-D, is a contraindication against the use of this technique.


Clinical overview of diabetes mellitus as a risk factor for cardiovascular death.
Global diabetes mellitus prevalence is increasing. Metabolic disorders, such as type 2 diabetes, are associated with abnormal cardiac electrophysiology and increased risk of arrhythmias. Patients with both diabetes types (1 and 2) suffer from sudden cardac death (SCD) as a leading cause of mortality. Cardiovascular death is defined as death attributable to cardiovascular disease (CVD) occurring shortly within the symptom onset. This usually arises from life-threatening ventricular tachyarrhythmias that lead to hemodynamic instability, and subsequent shock and death. A variety of pathways have been suggested that link hypoglycaemia to the development of adverse cardiovascular outcomes, including blood coagulation abnormalities, inflammation, endothelial dysfunction and sympathoadrenal responses. We propose a four-step framework for the optimisation of SCD risk factors in diabetic patients, to include: raising awareness to influence health behaviour, provision of screening programs, use of technology within educational programs to improve patient engagement and effective provision of diabetic community teams.


De Novo Transcriptome Assembly and Sex-Biased Gene Expression in the Cyclical Parthenogenetic Daphnia galeata.
Daphnia species have become models for ecological genomics and exhibit interesting features, such as high phenotypic plasticity and a densely packed genome with many lineage-specific genes. They are also cyclic parthenogenetic, with alternating asexual and sexual cycles and environmental sex determination. Here, we present a de novo transcriptome assembly of over 32,000 D. galeata genes and use it to investigate gene expression in females and spontaneously produced males of two clonal lines derived from lakes in Germany and the Czech Republic. We find that only a low percentage (18%) of genes shows sex-biased expression and that there are many more female-biased gene (FBG) than male-biased gene (MBG). Furthermore, FBGs tend to be more conserved between species than MBGs in both sequence and expression. These patterns may be a consequence of cyclic parthenogenesis leading to a relaxation of purifying selection on MBGs. The two clonal lines show considerable differences in both number and identity of sex-biased genes, suggesting that they may have reproductive strategies differing in their investment in sexual reproduction. Orthologs of key genes in the sex determination and juvenile hormone pathways, which are thought to be important for the transition from asexual to sexual reproduction, are present in D. galeata and highly conserved among Daphnia species.


Changes in outer retinal microstructures during six month period in eyes with acute zonal occult outer retinopathy-complex.
To study the changes in the outer retinal microstructures during a six month period after the onset of acute zonal occult outer retinopathy (AZOOR)-complex by spectral-domain optical coherence tomography (SD-OCT). Seventeen eyes of 17 patients with the AZOOR-complex were studied. The integrity of the external limiting membrane (ELM), ellipsoid zone (EZ; also called the inner/outer segment junction), and interdigitation zone (IDZ; also called the cone outer segment tips) were evaluated in the SD-OCT images obtained at the initial visit and at six months. The three highly reflective bands were divided into three types; continuous, discontinuous, and absent. The integrity of the outer nuclear layer (ONL) was also assessed. Among the three highly reflective bands, the IDZ was most altered at the initial visit and least recovered at six months. Fifteen of 17 eyes (88%) had a recovery of at least one of the three bands at six months in the retinal area where the ONL was intact, and these areas showed an improvement of visual field. Three eyes (18%) had retinal areas where the ONL was absent at the initial visit, and there was no recovery in both the retinal structures and visual fields in these areas. Our results indicate that more than 85% eyes with AZOOR-complex show some recovery in the microstructures of the outer retina during a six month period if the ONL is intact. We conclude that SD-OCT is a useful method to monitor the changes of the outer retinal microstructure in eyes with the AZOOR-complex.


Study of isotonic contrast media in intravenous digital subtraction angiography.
Arterial enhancement obtained with isotonic contrast media in intravenous digital subtraction angiography was studied. Ten dogs were injected with ioxaglate, iopamidol, and ioxitalamate at equal iodine concentration and at concentrations corresponding to plasma osmolality. Three variables were studied: osmolality, injection rate, and iodine dose. Provided their iodine concentration is sufficient, isotonic contrast media appear as efficient as the corresponding hypertonic formulation, at equal iodine dose. Moreover, the use of isotonic ioxaglate allows a lower dose of iodine to be administered without significant reduction in peak arterial value.


Familial eosinophilic fasciitis and breast cancer.
Eosinophilic fasciitis (EF) is an uncommon condition which unlike systemic sclerosis has only rarely been associated with solid malignancies. We report the occurrence of EF in two sisters, both of whom developed contemporaneous breast cancer.


A G-string positive cis-regulatory element in the LpS1 promoter binds two distinct nuclear factors distributed non-uniformly in Lytechinus pictus embryos.
The LpS1 alpha and beta genes of Lytechinus pictus are activated at the late cleavage stage of embryogenesis, with LpS1 mRNAs accumulating only in lineages contributing to aboral ectoderm. We had shown previously that 762 bp of 5' flanking DNA from the LpS1 beta gene was sufficient for proper temporal and aboral ectoderm specific expression. In the present study, we identified a strong positive cis-regulatory element at -70 bp to -75 bp in the LpS1 beta promoter with the sequence (G)6 and a similar, more distal cis-element at -721 bp to -726 bp. The proximal 'G-string' element interacted with two nuclear factors, one specific to ectoderm and one to endoderm/mesoderm nuclear extracts, whereas the distal G-string element interacted only with the ectoderm factor. The ectoderm and endoderm/mesoderm G-string factors were distinct based on their migratory behavior in electrophoretic mobility shift assays, binding site specificities, salt optima and EDTA sensitivity. The proximal G-string element shared homology with a binding site for the mammalian transcription factor IF1, a protein that binds to negative cis-regulatory elements in the mouse alpha 1(I) and alpha 2(I) collagen gene promoters. Competition experiments using wild-type and mutant oligonucleotides indicated that the ectoderm G-string factor and IF1 have similar recognition sites. Partially purified IF1 specifically bound to an oligonucleotide containing the proximal G-string of LpS1 beta. From our results, we suggest that the ectoderm G-string factor, a member of the G-rich DNA-binding protein family, activates the LpS1 gene in aboral ectoderm cells by binding to the LpS1 promoter at the proximal G-string site.


Maximum likelihood estimation for semiparametric transformation models with interval-censored data.
Interval censoring arises frequently in clinical, epidemiological, financial and sociological studies, where the event or failure of interest is known only to occur within an interval induced by periodic monitoring. We formulate the effects of potentially time-dependent covariates on the interval-censored failure time through a broad class of semiparametric transformation models that encompasses proportional hazards and proportional odds models. We consider nonparametric maximum likelihood estimation for this class of models with an arbitrary number of monitoring times for each subject. We devise an EM-type algorithm that converges stably, even in the presence of time-dependent covariates, and show that the estimators for the regression parameters are consistent, asymptotically normal, and asymptotically efficient with an easily estimated covariance matrix. Finally, we demonstrate the performance of our procedures through simulation studies and application to an HIV/AIDS study conducted in Thailand.


Characteristics of preterm delivery and low birthweight among 113,994 infants in Alberta: 1994-1996.
This study examined the impact of infant and maternal factors on preterm delivery and low birthweight (LBW) in Alberta between January 1, 1994 and December 31, 1996. Data on 113,994 births were collected from vital statistics registration birth data. Logistic regression models for preterm and LBW delivery suggested the key risk factors were multiple and still birth (odds ratios > 22.0). Other characteristics included female gender, birth defects, nulliparous women, maternal age 35 and greater, unmarried, history of abortion, maternal smoking, maternal street drug use, and having less than 4 prenatal visits (odds ratios 0.86-2.54). Interactions between smoking and alcohol, and smoking and parity were noted. Efforts to improve the currently low rates (8.2%) of smoking cessation during pregnancy are required. Social, economic and medical factors associated with delayed childbearing and birth outcomes should be investigated.


Differentiation of pathogenic and non-pathogenic Entamoeba: has the question been answered?
Pathogenic and non-pathogenic Entamoeba have been separated into two distinct species. Recently, the non-pathogenic E. dispar has been cultivated axenically. However, the genetic variability among different clones from the same strain, experimental production of hybrid clones which may differ from their parents, and the possibility of invasiveness of E. dispar, are some phenomena which may indicate that the last word on distinctiveness of the species has not yet been said.


[Integrated diagnosis of central pulmonary cancer].
The integrative diagnosis is based on a simultaneous analysis of the data obtained by various methods of examination. Nine direct and 14 indirect symptoms of central pulmonary carcinoma were distinguished. Three introscopic complexes, that helped a correct diagnosis, were used in examinations of 147 patients with this condition. The presence of direct symptoms and combinations of 3 or more indirect signs were regarded as a manifestation of cancer. Metastases to the lymph nodes of the root of the lung were detected in 57.1% of patients, metastases to the mediastinum in 32.7% of cases. The results of biopsy were positive in 93.9% of the patients. The suggested method extends the diagnostic potentialities of the routine methods of investigation and helps optimize the algorithm of examinations and detect the tumors that are difficult to recognize.


Machine learning based prediction and the influence of complement - Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial.
Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR. We carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome. A prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two proteins (coagulation factor IX and complement C5) positively associated with the PSS score. Our study does not provide support for the utility of cytokines, proteomic or fatty acid data for prediction of functional outcomes in individuals at high-risk for psychosis. However, the association of complement protein levels with clinical outcome suggests a role for the complement system and the activity of its related pathway in the functional impairment and positive symptom severity of CHR patients.


Structural and functional aspects of rat microsomal glutathione transferase. The roles of cysteine 49, arginine 107, lysine 67, histidine, and tyrosine residues.
Rat liver microsomal glutathione transferase is rapidly inactivated upon treatment with the arginine-selective reagent phenylglyoxal or the lysine-selective 1,3,5-trinitrobenzenesulfonate. Glutathione sulfonate, an inhibitor of the enzyme, gives nearly complete protection against inactivation and prevents modification, indicating that these residues form part of or reside close to the active site. Sequence analysis of peptides from peptic and tryptic digests of [7-14C]phenylglyoxal- and 1,3,5-trinitrobenzenesulfonate-treated microsomal glutathione transferase indicated arginine 107 and lysine 67 as the sites of modification. A set of mutant forms of microsomal glutathione transferase was constructed by site-directed mutagenesis and heterologously expressed in Escherichia coli BL21(DE3). Arginine 107 was exchanged for alanine and lysine residues. The alanine mutant (R107A) exhibited an activity and inhibition profile similar to that of the wild type enzyme but displayed a decreased thermostability. Thus, arginine 107 does not appear to participate in catalysis or substrate binding; instead, an important structural role is suggested for this residue. Lysine 67 was mutated to alanine and arginine with no effect on activity. All three histidines were replaced by glutamine, and the resulting mutant proteins had activities comparable with that of the wild type. It can thus be concluded that the chemical modification experiments indicating that arginine 107, lysine 67, and one of the histidines partake in catalysis can be disproved. However, protection from modification by a competitive inhibitor indicates that these residues could be close to the glutathione binding site. All tyrosine to phenylalanine substitutions resulted in mutants with activities similar to that of the wild type. Interestingly, the exchange of tyrosine 137 appears to result in activation of the enzyme. Thus, the microsomal glutathione transferase must display an alternate stabilization of the thiolate anion of glutathione other than through interaction with the phenolic hydroxyl group of a tyrosine residue. Substitution of cysteine 49 with alanine resulted in a semiactivated mutant enzyme with enzymatic properties partly resembling the activated form of microsomal glutathione transferase. The function of this mutant was not altered upon reaction with N-ethylmaleimide, and cysteine 49 is thus demonstrated as the site of modification that results in activation of microsomal glutathione transferase.


Genomic and phylogenetic characterization of Merino Walk virus, a novel arenavirus isolated in South Africa.
Merino Walk virus (MWV), a proposed novel tentative species of the family Arenaviridae, was isolated from a rodent, Myotomys unisulcatus, collected at Merino Walk, Eastern Cape, South Africa, in 1985. Full-length genomic sequence confirmed MWV as an arenavirus related distantly to Mobala, Mopeia and Ippy viruses, all members of the Old World arenavirus complex. We propose MWV as a tentative novel species in the Lassa-lymphocytic choriomeningitis virus complex, based on its isolation from a novel rodent species and its genetic and serological characteristics.


Effects of agrin on the expression and distribution of the water channel protein aquaporin-4 and volume regulation in cultured astrocytes.
Agrin is a heparan sulfate proteoglycan of the extracellular matrix and is known for organizing the postsynaptic differentiation of the neuromuscular junction. Increasing evidence also suggests roles for agrin in the developing CNS, including the formation and maintenance of the blood-brain barrier. Here we describe effects of agrin on the expression and distribution of the water channel protein aquaporin-4 (AQP4) and on the swelling capacity of cultured astrocytes of newborn mice. If astrocytes were cultured on a substrate containing poly DL-ornithine, anti-AQP4 immunoreactivity was evenly and diffusely distributed. If, however, astrocytes were cultured in the presence of agrin-conditioned medium, we observed an increase in the intensity of AQP4-specific membrane-associated staining. Freeze-fracture studies revealed a clustering of orthogonal arrays of particles, representing a structural equivalent of AQP4, when exogenous agrin was present in the astrocyte cultures. Neuronal and non-neuronal agrin isoforms (agrin A0B0 and agrin A4B8, respectively) were able to induce membrane-associated AQP4 staining. Water transport capacity as well as the density of orthogonal arrays of intramembranous particles was increased in astrocytes cultured with the neuronal agrin isoform A4B8, but not with the endothelial and meningeal isoform A0B0. RT-PCR demonstrated that agrin A4B8 increased the level of the M23 splice variant of AQP4 and decreased the level of the M1 splice variant of AQP4. Implications for the regulation and maintenance of the blood-brain barrier including oedema formation under pathological conditions are discussed.


Anxiety Sensitivity is Associated with Lower Enjoyment and an Anxiogenic Response to Physical Activity in Smokers.
The subjective affective response to, and enjoyment of, physical activity are strong predictors of engagement in physical activity. Anxiety sensitivity, the fear of bodily sensations, is a cognitive factor that may inhibit the pleasurable affective experience of physical activity, possibly contributing to low levels of physical activity. The current study evaluated anxiety sensitivity in relation to PA enjoyment and affective experience before and after exercise in smokers. Participants were low-active treatment-seeking smokers (n = 201) enrolled in a smoking cessation intervention. At baseline, participants completed self -report assessments of anxiety sensitivity, cigarette dependence, and physical activity enjoyment. State affect was also reported before and after a submaximal exercise test to index pre-exercise activity affect and affective response to exercise. Anxiety sensitivity was significantly negatively correlated with physical activity enjoyment, specifically lower enjoyable physical feelings of physical activity. Anxiety sensitivity was significantly correlated with lower state mood and higher state anxiety prior to the submaximal exercise test, and higher anxiety immediately after the exercise test. Additionally, anxiety sensitivity predicted increased anxiety, but not lower mood, in response to the submaximal exercise test. This is the first study to document an association of anxiety sensitivity with affective determinants of physical activity behavior in smokers. Anxiety sensitivity was associated with lower physical activity enjoyment, higher negative affect prior to after exercise testing, and an anxiogenic response to exercise. Future work is needed to understand how the current findings generalize beyond smokers.


Exploring the mechanism of Grignard metathesis polymerization of 3-alkylthiophenes.
In this study we have investigated computationally the mechanism of polymerization of 2,5-dibromo 3-butylthiophene via the GRIM method, with the focus on the origin of the head to tail (HT) selectivity. To this end, first the Grignard reagent underwent oxidative addition to the monomer to afford the 2-bromo-5-chloromagnesio-3-butylthiophene (intermediate I1) or the 2-chloromagnesio 5-bromo-3-butylthiophene (intermediate I2) regioisomers. Then intermediates I1 and I2 were polymerized catalytically to a series of regiospecific poly-3-butylthiophenes using the commonly used Ni(dppp)Cl2 [dppp: 1,3-bis(diphenylphosphino) propane] and Pd(dppp)Cl2 catalysts. Due to the asymmetric nature of I1 and I2 that act as the active monomeric species, 6 coupling modes may occur. The whole energy profile of all modes has been studied by considering a three-stage mechanism, including coordination, transmetalation, and reductive elimination, to compare quantitatively the ability of so-called catalysts in selective coupling of desired isomers to produce regioregular poly-3-butylthiophene. Finally, to quantify the steric role of the dppp in regioselectivity, analysis of the buried volume in terms of steric maps was performed.


Subcortical connections of subdivisions of inferior temporal cortex in squirrel monkeys.
On the basis of cortical connections and architectonics, inferior temporal (IT) cortex of squirrel monkeys consists of a caudal, prestriate-recipient region, ITC; a rostral region, ITR; and possibly an intermediate region along the border of ITC and ITR, "ITI" (Weller & Steele, 1992). ITC contains dorsal (ITCd) and ventral (ITCV) areas. The subcortical connections of these subdivisions of IT cortex were determined in the present study from the results of cortical injections of wheat-germ agglutinin conjugated to horseradish peroxidase, [3H]-amino acids and fast blue. ITC and ITR receive afferents from the locus coeruleus, dorsal raphe, nucleus annularis, central superior nucleus, pontine reticular formation, lateral hypothalamus, paracentral nucleus, and central medial nucleus; send efferents to the superior colliculus, reticular nucleus, and striatum; and have both afferent and efferent connections with the pretectum, pulvinar, claustrum, amygdala, and basal nucleus of Meynert. ITC and ITR have different patterns of connections with a number of subcortical structures, including the pulvinar and amygdala. Injections in ITC strongly label multiple nuclei of the inferior pulvinar and the medial division of the lateral pulvinar (PLM), and moderately label the medial pulvinar (PM), whereas injections in ITR strongly label PM and moderately label PLM. Injections in ITC label sparse projections to the lateral nucleus of the amygdala, in contrast to injections in ITR that label strong projections to the lateral and basal nuclei of the amygdala. Injections in "ITI" produce a pattern of subcortical label that has some features of that observed from injections in ITC and that observed from injections in ITR. Although most of the connections of ITCd and ITCv appear similar, only injections involving ITCd label the middle nucleus of the inferior pulvinar (PIM). Comparison of the subcortical connections of subdivisions of IT cortex in squirrel monkeys and what is presently known of the subcortical connections of subdivisions of IT cortex in macaque monkeys supports the previous suggestion that ITC of squirrel monkeys may be comparable to area TEO of macaques, ITI may be comparable to posterior area TE, and ITR may be comparable to anterior area TE (Weller & Steele, 1992).


Combining pairwise structural similarity and deep learning interface contact prediction to estimate protein complex model accuracy in CASP15.
Estimating the accuracy of quaternary structural models of protein complexes and assemblies (EMA) is important for predicting quaternary structures and applying them to studying protein function and interaction. The pairwise similarity between structural models is proven useful for estimating the quality of protein tertiary structural models, but it has been rarely applied to predicting the quality of quaternary structural models. Moreover, the pairwise similarity approach often fails when many structural models are of low quality and similar to each other. To address the gap, we developed a hybrid method (MULTICOM_qa) combining a pairwise similarity score (PSS) and an interface contact probability score (ICPS) based on the deep learning inter-chain contact prediction for estimating protein complex model accuracy. It blindly participated in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 and ranked first out of 24 predictors in estimating the global accuracy of assembly models. The average per-target correlation coefficient between the model quality scores predicted by MULTICOM_qa and the true quality scores of the models of CASP15 assembly targets is 0.66. The average per-target ranking loss in using the predicted quality scores to rank the models is 0.14. It was able to select good models for most targets. Moreover, several key factors (i.e., target difficulty, model sampling difficulty, skewness of model quality, and similarity between good/bad models) for EMA are identified and analayzed. The results demonstrate that combining the multi-model method (PSS) with the complementary single-model method (ICPS) is a promising approach to EMA. The source code of MULTICOM_qa is available at https://github.com/BioinfoMachineLearning/MULTICOM_qa .


Intervertebral disc prosthesis. Results and prospects for the year 2000.
Presently, the kinematic disc prosthesis model (SB Charité) is the best disc replacement compromise, and is the basis of the evolution of the prosthetic concept at the dawning of the year 2000. Clinical results of a homogeneous series of 105 cases with a mean followup of 51 months show 79% of the patients had an excellent result and 87% returned to work, radiologically, these results correlated with restoration of a well balanced lordosis and with segmental mobility. Factors leading to failure are posterior facet arthritis, osteoporosis, structural deformities, and secondary facet pain. Two- and 3-dimensional numeric modeling enables one to study the total facet joint loading and the maximal local loading on the facet. Dissociation of the stiffness in pure rotation and stiffness in translation of the disc are the bases of the technologic improvement.


Quota implementation of the maximum sustainable yield for age-structured fisheries.
One of the main goals stated in the proposals for the Common Fisheries Policy (CFP) reform was achieving maximum sustainable yield (MSY) for all European fisheries. In this paper, we propose a fishing rights allocation mechanism or management system, which specifies catch limits for individual fishing fleets to implement MSY harvesting conditions in an age-structured bioeconomic model. An age-structured model in a single species fishery with two fleets having perfect or imperfect fishing selectivity is studied. If fishing technology or gear selectivity depends on the relative age composition of the mature fish stock, fixed harvest proportions, derived from catchability and bycatch coefficients, is not valid anymore. As a result, not only the age-structure and fishing technology but also the estimated level of MSY is steering the allocation of quota shares. The results also show that allocation of quota shares based on historical catches or auctioning may not provide viable solutions to achieve MSY.


Patient administrative burden in the US health care system.
To assess the prevalence of patient administrative tasks and whether they are associated with delayed and/or foregone care. March 2019 Health Reform Monitoring Survey. We assess the prevalence of five common patient administrative tasks-scheduling, obtaining information, prior authorizations, resolving billing issues, and resolving premium problems-and associated administrative burden, defined as delayed and/or foregone care. Using multivariate logistic models, we examined the association of demographic characteristics with odds of doing tasks and experiencing burdens. Our outcome variables were five common types of administrative tasks as well as composite measures of any task, any delayed care, any foregone care, and any burden (combined delayed/foregone), respectively. We developed and administered survey questions to a nationally representative sample of insured, nonelderly adults (n = 4155). The survey completion rate was 62%. Seventy-three percent of respondents reported performing at least one administrative task in the past year. About one in three task-doers, or 24.4% of respondents overall, reported delayed or foregone care due to an administrative task: Adjusted for demographics, disability status had the strongest association with administrative tasks (adjusted odds ratio [OR] 2.91, p < 0.001) and burden (adjusted OR 1.66, p < 0.001). Being a woman was associated with doing administrative tasks (adjusted OR 2.19, p < 0.001). Being a college graduate was associated with performing an administrative task (adjusted OR 2.79, p < 0.001), while higher income was associated with fewer subsequent burdens (adjusted OR 0.55, p < 0.01). Patients frequently do administrative tasks that can create burdens resulting in delayed/foregone care. The prevalence of delayed/foregone care due to administrative tasks is comparable to similar estimates of cost-related barriers to care. Demographic disparities in burden warrant further attention. Enhancing measurement of patient administrative work and associated burdens may identify opportunities for assessing quality, value, and patient experience.


Clinical terms project: a coding system for clinicians.
Advances in information management and technology are necessary for improved communication, research and resource management in the health service. The medical profession must be closely involved in the development of a computer-based communications network if it is to be clinically useful and acceptable. The Read codes have been developed by clinicians and form the basis of an entire clinical information system.


Reprint requests for family medicine literature: how do we respond?
Requesting and sending reprints of articles published in the medical literature is an established tradition. This survey of authors of family medicine literature found that 54% believed the tradition should be continued, and 43% felt reprints meet a real need. The authors responded to 90% of the requests. Those authors who paid the cost out of their own pockets were significantly more likely to view reprints as useful and more likely to respond to requests. Support for innovative ways of disseminating information, ways that may meet needs that reprints do not, is potentially available.


The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease.
We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.


Intra- and extra-familial child homicide in Sweden 1992-2012: A population-based study.
Previous studies have shown decreasing child homicide rates in many countries - in Sweden mainly due to a drop in filicide-suicides. This study examines the rate of child homicides during 21 years, with the hypothesis that a decline might be attributable to a decrease in the number of depressive filicide offenders (as defined by a proxy measure). In addition, numerous characteristics of child homicide are presented. All homicide incidents involving 0-14-year-old victims in Sweden during 1992-2012 (n = 90) were identified in an autopsy database. Data from multiple registries, forensic psychiatric evaluations, police reports, verdicts and other sources were collected. Utilizing Poisson regression, we found a 4% annual decrease in child homicides, in accordance with prior studies, but no marked decrease regarding the depressive-offender proxy. Diagnoses from forensic psychiatric evaluations (n = 50) included substance misuse (8%), affective disorders (10%), autism-spectrum disorders (18%), psychotic disorders (28%) and personality disorders (30%). Prior violent offences were more common among offenders in filicides than filicide-suicides (17.8% vs. 6.9%); and about 20% of offenders in each group had previously received psychiatric inpatient care. Aggressive methods of filicide predominated among fathers. Highly lethal methods of filicide (firearms, fire) were more commonly followed by same-method suicide than less lethal methods. Interestingly, a third of the extra-familial offenders had an autism-spectrum disorder. Based on several findings, e.g., the low rate of substance misuse, the study concludes that non-traditional risk factors for violence must be highlighted by healthcare providers. Also, the occurrence of autism-spectrum disorders in the present study is a novel finding that warrants further investigation.


Vindesine for recurrent and metastatic cancer of the uterine cervix: a phase II study.
Twenty-four patients with recurrent or metastatic cervical cancer were treated with vindesine (VDS) (2 mg/m2) on 2 subsequent days per week. Twenty patients were evaluable for response. There were six partial responses (30%) and no complete responses. The median remission duration was 6.5 months. The results indicate that VDS is active in the treatment of cervical cancer. Dose-limiting toxic effects were leukopenia and peripheral neuropathy. VDS should be considered in the treatment planning of combination chemotherapy for cervical cancer.


Influence of environmental conditions on early development of the hydrothermal vent polychaete Alvinella pompejana.
Dispersal and colonisation processes at deep-sea vents are still not fully understood, essentially because early life stages of vent species remain unknown. The polychaete worm Alvinella pompejana forms colonies on chimney walls at East Pacific Rise vent sites where the temperature can frequently exceed 20 degrees C. In vitro studies in pressure vessels showed that the early embryos tolerate temperatures in a lower range (10-14 degrees C), suggesting that they would have to escape the colony to develop. Pressure vessels offer the advantage that each parameter can be independently controlled, but they do not simulate the more complex and dynamic conditions naturally encountered at vent sites. Accordingly, in addition to incubations in pressure vessels, we incubated embryos directly at a vent site, in different habitats along a gradient of hydrothermal influence. Embryos incubated on an adult A. pompejana colony where temperature and H(2)S concentrations were relatively high showed a very low survival rate and did not develop, whereas embryos incubated in a Riftia pachyptila clump environment with a lower hydrothermal signature, or at the base of the chimney where the influence of the hydrothermal activity was very weak, survived well and developed. Although the average temperature recorded in the A. pompejana colony was within the range tolerated by embryos (13 degrees C), frequent peaks above 20 degrees C were recorded. Estimated sulphide concentration at this site reached 200 mumol l(-1). Punctuated exposure to both high temperature and elevated sulphide levels probably explain the low survival of embryos within the A. pompejana colony. The in situ experiments further support the idea that embryos require conditions with moderate hydrothermal influence not generally found within an adult colony. However, as much more benign physicochemical conditions can be found within a few tens of cm of adult colonies, embryos do not necessarily have to leave their vent of origin to develop. Further analyses are needed to pinpoint the specific factors that affect the survival and development of embryos at vents.


Preservation of myocardial function by mechanical circulatory support during prolonged ischaemia.
The effect of mechanical circulatory support on left ventricular (LV) function was evaluated during prolonged myocardial ischaemia. Regional wall thickening of a normal and an ischaemic LV region were determined in eight calves (mean body weight 76 kg) using pairs of ultrasonic crystals. LV end-diastolic (mmHg) and peak systolic (mmHg) pressure as well as maximum dP/dt (mmHg s-1) were calculated from LV high-fidelity pressure tracings. The left circumflex coronary artery was ligated proximally for 6 h and reperfused for 18 h. Circulatory support by the assist device was performed from the beginning of ischaemia to the end of the experiment. After a mean time of 4 h all animals showed ventricular fibrillation, which was converted successfully in six animals after a mean time interval of 5 h. Five animals survived after 24 h. The non-surviving animals had larger infarcts, greater creatine kinase release and a larger drop in cardiac output during ischaemia. Haemodynamic measurements were carried out after turning off the assist device. Inotropic stimulation with 0.68 mg.min-1 dopamine i.v. was performed at the end of the study. LV regional function showed systolic bulging during myocardial ischaemia. After 18 h of reperfusion, the ischaemic wall recovered and showed normal systolic wall thickening in the presence of an increased LV preload. LV relaxation was prolonged after reperfusion, suggesting diastolic dysfunction. It is concluded that mechanical circulatory support is effective in protecting myocardial function during prolonged ischaemia in approximately two-thirds of the animals, despite severe ischaemic ventricular dysfunction and intermittent ventricular fibrillation.


Innovative composite films of chitosan, methylcellulose, and nanoparticles.
Plastic is readily available and inexpensive, so it is becoming the main material for packaging. Unfortunately plastics do not biodegrade and, if reduced in small pieces, contaminate soil and waterways. In the present work, natural films composed of chitosan, methylcellulose, and silica (SiO(2)) nanoparticles (NPs) were developed as new packaging materials. The effect of the incorporation of NPs into the polymeric film matrix was evaluated. An excellent improvement of the mechanical properties was obtained for nanostructured films with a composition of CH:MC 50:50 and NPs 1% w/v that make these materials able to replace plastics and derivatives, reducing environmental pollution.


Dynamic Radiostereometry Evaluation of 2 Different Anterior Cruciate Ligament Reconstruction Techniques During a Single-Leg Squat.
Lateral extra-articular tenodesis in the context of anterior cruciate ligament (ACL) reconstruction (ACLR) is performed to better control anterolateral knee instability in patients with high-grade preoperative pivot shift. However, some authors believe these procedures may cause lateral compartment overconstraint, affecting knee motion in daily life. The primary aim of the present study was to identify kinematic differences during the execution of an activity under weightbearing conditions between knees having undergone ACLR using anatomic single-bundle (SB) versus single-bundle plus lateral plasty (SBLP) techniques. The secondary aim was to compare the postoperative kinematic data with those from the same knees before ACLR and from the healthy contralateral knees in order to investigate if ACLR was able to restore physiologic knee biomechanics during squat execution. The hypotheses were that (1) the SBLP technique would allow a better restoration of internal-external (IE) knee rotation than would SB and (2) regardless of the technique, ACLR would not fully restore physiologic knee biomechanics. Randomized controlled trial; Level of evidence, 2. In total, 32 patients (42 knees) were included in the study. Patients were asked to perform a single-leg squat before surgery (ACL-injured group, n = 32; healthy contralateral group, n = 10) and at minimum 18-month follow-up after ACLR (SB group, n = 9; SBLP group, n = 18). Knee motion was determined using a validated model-based tracking process that matched patient-specific magnetic resonance imaging bone models to dynamic biplane radiographic images under the principles of roentgen stereophotogrammetric analysis. Data processing was performed using specific software. The authors compared IE and varus-valgus rotations and anterior-posterior and medial-lateral translations among the groups. The mean follow-up period was 21.7 ± 4.5 months. No kinematic differences were found between the SB and SBLP groups (P > .05). A more medial tibial position (P < .05) of the ACL-injured group was reported during the entire motor task and persisted after ACLR in both the SB and the SBLP groups. Differences in IE and varus-valgus rotations were found between the ACL-injured and healthy groups. There were no relevant kinematic differences between SBLP and anatomic SB ACLR during the execution of a single-leg squat. Regardless of the surgical technique, ACLR failed in restoring knee biomechanics. NCT02323386 (ClinicalTrials.gov identifier).


Ventilatory pattern following diphtheria-tetanus-pertussis immunization in infants at risk for sudden infant death syndrome.
To evaluate the effects of diphtheria-tetanus-pertussis (DTP) immunization on the ventilatory pattern during sleep in infants at increased risk for sudden infant death syndrome (SIDS), we performed overnight pneumograms (recordings of ventilatory pattern and electrocardiogram) on 30 control infants, 46 infants with unexplained apnea, and 33 subsequent siblings of SIDS victims the night before and the night following a DTP immunization. Pneumograms were quantitated for total sleep time, longest apnea (in seconds), total duration of apneas longer than 6 s (in minutes), and total periodic breathing (in minutes). Following the DTP immunization there was no significant change in any criterion quantitated on pneumograms from any group except for a decrease in periodic breathing in the unexplained apnea group. We conclude that DTP immunization does not increase abnormalities of the ventilatory pattern as recorded by the pneumogram technique in infants at increased risk for SIDS.


Genetic risk assessment in breast and gynecologic malignancies- what's to know in 2024?
Hereditary cancer risk assessment and counseling have become integral in oncology care, especially in breast and gynecologic malignancies where genetic test results impact management. However, a large number of patients who could benefit from genetic testing are not getting tested. As such, genetic risk assessment and counseling methods have had to evolve to meet the needs of this expanding patient population. "Mainstreaming" genetic testing is an initiative to incorporate genetic testing into routine cancer care in lieu of the traditional genetic counseling model to improve uptake of testing while minimizing expansion of genetic counselor and clinic resources. These models have performed well in various institutions demonstrating an improvement in clinical efficacy. However, missed opportunities from the preventive care standpoint, a core value of cancer genetics risk assessment, have become apparent. The focus of these models is on the patient's cancer diagnosis and comprehensive/familial genetic risk assessment is not often completed. Identifying patients at an increased risk of cancer, even in the absence of a hereditary cancer predisposition syndrome, is important in tailoring screening and preventive measures. As we look to the future, we need to critically approach mainstreaming and determine how to reincorporate comprehensive genetic risk assessment into our models.


Subcutaneous implantable cardioverter-defibrillator implantation in a patient with a left ventricular assist device already in place.
A 56-year-old man with ischemic cardiomyopathy, a biventricular implantable cardioverter-defibrillator (ICD), and a left ventricular assist device (LVAD) developed a pocket hematoma and infection after an ICD generator change. The biventricular ICD was extracted, and the patient was given a full course of antibiotics. Because he had no indications for bradycardia pacing or biventricular pacing, he was implanted with a subcutaneous ICD under full anticoagulation. There was no interference in sensing or shock delivery from the ICD. The LVAD readings were unchanged during and after the procedure. The patient had an uneventful postoperative course, and both devices were functioning normally. To our knowledge, this is the first reported case of the implantation of a subcutaneous ICD in the presence of an LVAD. This report illustrates that both devices can be implanted successfully in the same patient. In addition, the subcutaneous ICD minimizes the risk of bloodstream infections, which can be fatal in patients who have life-supporting devices such as an LVAD.


Impact of work site health promotion on stages of dietary change: the Working Well Trial.
The stages of change construct has been applied to healthful dietary behavior in cross-sectional studies. This report examines associations of stages of change with diet prospectively and addresses whether (1) baseline stage of change predicts participation, (2) forward changes in stage movement were greater in treatment work sites, and (3) change in stage was associated with adoption of healthful diets, using data from a cohort of 11,237 employees. Findings indicate that persons in later stages of change reported higher participation levels. Employees from intervention work sites who were in preaction stages at baseline were much more likely to shift into action and maintenance stages than controls. Changes in dietary stage of change were associated with decreases in fat intake and increases in fiber, fruit and vegetable intake. Net change in diet due to the intervention was modest. Stage of change appears to be useful for understanding mediators of health promotion intervention effectiveness.


Multi-Toxin Occurrences in Ten French Water Resource Reservoirs.
Cyanobacteria are known to produce a wide array of metabolites, including various classes of toxins. Among these, hepatotoxins (Microcystins), neurotoxins (Anatoxin-A and PSP toxins) or cytotoxins (Cylindrospermopsins) have been subjected to numerous, individual studies during the past twenty years. Reports of toxins co-occurrences, however, remain scarce in the literature. The present work is an inventory of cyanobacteria with a particular focus on Nostocales and their associated toxin classes from 2007 to 2010 in ten lakes used for drinking water production in France. The results show that potential multiple toxin producing species are commonly encountered in cyanobacteria populations. Individual toxin classes were detected in 75% of all samples. Toxin co-occurrences appeared in 40% of samples as two- or three-toxin combinations (with 35% for the microcystins⁻anatoxin combination), whereas four-toxin class combinations only appeared in 1% of samples. Toxin co-occurrences could be partially correlated to species composition and water temperature. Peak concentrations however could never be observed simultaneously and followed distinct, asymmetrical distribution patterns. As observations are the key for preventive management and risk assessment, these results indicate that water monitoring should search for all four toxin classes simultaneously instead of focusing on the most frequent toxins, i.e., microcystins.


A mathematical model to predict short-term recurrence and metastasis of primary hepatocellular carcinoma larger than 10 cm in diameter.
To construct a mathematical model to predict short-term recurrence and metastasis of primary hepatocellular carcinoma (HCC) larger than 10 cm in diameter after radical resection and analyze the influencing factors. A total of 166 patients with primary HCC larger than 10 cm were recruited from January 2002 to December 2010. Univariable and multivariable logistic regression analyses were performed and a mathematic model predicting the recurrence of HCC at different time points was constructed. Univariable analysis showed preoperative serum AFP of ≥1210 ng/mL (X4), intraoperative macroscopic tumor thrombus (X7) and postoperative pathological grade (X11) were related to the recurrence within 6 months after surgery. Preoperative serum AFP of ≥1210 ng/mL (X4) and microscopic tumor thrombus (X10) were associated with the recurrence within 6-12 months after surgery. Multivariable analysis revealed the risk factors of recurrence within 6 months and 6-12 months after surgery included preoperative serum AFP of ≥1210 ng/mL (X4) and intra-operative macroscopic tumor thrombus (X7); those within 6-12 months after surgery were preoperative serum AFP of ≥1210 ng/mL (X4) and microscopic tumor thrombus (X10). Preoperative serum AFP and blood vessel involvement are risk factors of short-term recurrence/metastasis of huge HCC after surgery. The equation for prediction of HCC recurrence at different time points varies.


[Management of smoking cessation in general practice].
Tobacco is a major health problem leading to 20.000 deaths between the ages of 35 and 69 each year in Belgium. This is the reason why all general practitioners should be concerned about this problem and mainly because there is existing evidence that some of their simple professional attitudes accompanying smoking cessation could be effective. This article proposes all valid attitudes adapted for the management of smoking cessation in primary care, not only for adults but also for adolescents.


A Variable Height Microfluidic Device for Multiplexed Immunoassay Analysis of Traumatic Brain Injury Biomarkers.
Traumatic brain injury (TBI) is a leading cause of global morbidity and mortality, partially due to the lack of sensitive diagnostic methods and efficacious therapies. Panels of protein biomarkers have been proposed as a way of diagnosing and monitoring TBI. To measure multiple TBI biomarkers simultaneously, we present a variable height microfluidic device consisting of a single channel that varies in height between the inlet and outlet and can passively multiplex bead-based immunoassays by trapping assay beads at the point where their diameter matches the channel height. We developed bead-based quantum dot-linked immunosorbent assays (QLISAs) for interleukin-6 (IL-6), glial fibrillary acidic protein (GFAP), and interleukin-8 (IL-8) using DynabeadsTM M-450, M-270, and MyOneTM, respectively. The IL-6 and GFAP QLISAs were successfully multiplexed using a variable height channel that ranged in height from ~7.6 µm at the inlet to ~2.1 µm at the outlet. The IL-6, GFAP, and IL-8 QLISAs were also multiplexed using a channel that ranged in height from ~6.3 µm at the inlet to ~0.9 µm at the outlet. Our system can keep pace with TBI biomarker discovery and validation, as additional protein biomarkers can be multiplexed simply by adding in antibody-conjugated beads of different diameters.


Prevalence and determinants of online-sex use in the German population.
The unlimited access to sexual features in the World Wide Web has raised concerns about excessive and problematic online-sex use. However, little is known about antecedents of internet-sex use of different intensity. Based on a representative German sample of 2,522 participants between the ages of 14 and 97 years, the aims of the present study were (1) to determine the prevalence rates of online-sex users with the short version (ISSTGSV) of the Internet Sex Screening Test and (2) to associate online-sex use with anxious vs. avoidant partner attachment patterns and "Big Five" personality traits as potential antecedents. The ISST is a brief, one-dimensional and reliable measure of online-sex activities (rtt = .69). Overall, 14.7% of respondents reported occasional and 4.2% intensive online-sex use. In multivariate analysis, online-sex use was significantly positively associated with male sex, younger age, unemployment and an anxious partner attachment pattern and negatively with conscientiousness and agreeableness. Arousal and satisfaction by virtual enactment of sexual phantasies may be attractive for anxiously attached persons who find it difficult to commit to a real life relationship due to fear of rejection or low self-esteem. More knowledge about the individual antecedents of intensive online-sex use may also be helpful for the development of consultation and treatment strategies for excessive and addictive online-sex use.


Plasma phospholipid transfer protein activity is related to insulin resistance: impaired acute lowering by insulin in obese Type II diabetic patients.
Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) have important functions in high density lipoprotein (HDL) metabolism. We determined the association of plasma CETP and PLTP activities (measured with exogenous substrate assays) with insulin resistance, plasma triglycerides (TG) and non-esterified fatty acids (NEFA), and assessed the lipid transfer protein response to insulin during a 6-7 h hyperinsulinaemic euglycaemic clamp in non-obese and obese healthy subjects and patients with Type II (non-insulin-dependent) diabetes mellitus (n = 8 per group). Plasma PLTP activity was higher in obese healthy subjects and obese Type II diabetic patients compared with non-obese healthy subjects (p < 0.05 to 0.01) and was correlated with insulin resistance, plasma TG and NEFA (p = 0.02 to < 0.01). In non-obese healthy subjects, insulin decreased plasma TG and increased the HDL cholesteryl ester (CE)/TG ratio (p < 0.01 compared with saline infusion). Plasma PLTP activity fell by 14% at the end of the clamp (p < 0.01 compared with saline) but CETP activity did not change. The decreases in plasma NEFA, TG and PLTP activity and the rise in HDL CE/TG were smaller in obese Type II diabetic patients than in non-obese healthy subjects (p < 0.01 for all). Baseline HDL CE/TG was negatively correlated with plasma TG (p < 0.001, n = 32) and PLTP activity (p < 0.01) but not with CETP activity. Likewise, the rise in HDL CE/TG during the clamp was related to the fall in plasma TG (p < 0.001) and in PLTP activity (p < 0.02). It is concluded that plasma PLTP, but not CETP, is regulated by insulin in an acute setting. High plasma PLTP activity is associated with insulin resistance in conjunction with altered NEFA and triglyceride metabolism. High plasma TG and PLTP activity have coordinate effects on HDL metabolism.


Optimization of beta-carotene production by Rhodotorula glutinis using high hydrostatic pressure and response surface methodology.
Rhodotorula glutinis RG6 was treated by high hydrostatic pressure (HHP) of 300 MPa for 15 min for improving its ability of beta-carotene production. After the treatments of 5 repeated cycles, the mutant strain RG6p was obtained, beta-carotene production of which reached 10.01 mg/L, increased by 57.89% compared with 6.34 mg/L from parent strain RG6. To optimize the medium for beta-carotene fermentation by mutant RG6p, a response surface methodology (RSM) approach was used in conjunction with a factorial design and a central composite design, and the maximum yield of beta-carotene (13.43 mg/L), an increase of 34.17% compared to the control, was obtained at a pH 6.7 with an optimum medium (40 mL/250 mL) of yeast extract (4.23 g/L), glucose (12.11 g/L), inoculum (30 mL/L), tomato extract (2.5 mL/L), peanut oil (0.5 mL/L), and (NH(4))(2)SO(4) (5 g/L).


A Systematic Review of the World's Largest Government Sponsored Health Insurance Scheme for 500 Million Beneficiaries in India: Pradhan Mantri Jan Arogya Yojana.
In pursuit of universal health coverage, India has launched the world's largest government-sponsored health insurance scheme, Pradhan Mantri Jan Arogya Yojana (PM-JAY) in 2018. This study aims to provide a holistic review of the scheme's impact since its inception. We reviewed studies (based on interviews or surveys) published from September 2018 to January 2023, which were retrieved from PubMed, Web of Science, and Scopus database. The main outcomes studied were: (1) awareness; (2) utilization of scheme; (3) experiences; (4) financial protection; and (5) challenges encountered by both beneficiaries and healthcare providers. A total of 18 studies conducted across 14 states and union territories of India were reviewed. The findings revealed that although PM-JAY has become a familiar name, there remains a low level of awareness regarding various facets of the scheme such as benefits entitled, hospitals empanelled, and services covered. The scheme is benefitting the poor and vulnerable population to access healthcare services that were previously unaffordable to them. However, financial protection provided by the scheme exhibited mixed results. Several challenges were identified, including continued spending by beneficiaries on drugs and diagnostic tests, delays in issuance of beneficiary cards, and co-payments demanded by healthcare providers. Additionally, private hospitals expressed dissatisfaction with low health package rates and delays in claims reimbursement. Concerted efforts such as population-wide dissemination of clear and complete knowledge of the scheme, providing training to healthcare providers, addressing infrastructural gaps and concerns of healthcare providers, and ensuring appropriate stewardship are imperative to achieve the desired objectives of the scheme in the long-run.


Legal Issues for the Medical Director.
The nephrologist serving as medical director of a dialysis clinic must understand that the role of director is not simply an extension of being a good nephrologist. The two roles-nephrology practice and the leadership of a dialysis clinic-may be filled by a single person. However, each role contains unique tasks, requiring specific skill sets, and each role comes with inherent, associated legal risks. The medical director assumes a new level of responsibility and accountability defined by contractual obligations to the dialysis provider and by state and federal regulations. Hence, a medical director is accountable not only for providing standard-of-care treatment to his or her private practice patients dialyzed at the clinic but also for maintaining the safety of the dialysis clinic patient population and staff. Accordingly, a nephrologist serving in the role of medical director faces distinct legal risks beyond typical professional liability concerns. The medical director must also be mindful of regulatory compliance, unique avenues to licensure board complaints, and implications of careless communication habits. A thoughtful and prepared medical director can mitigate these risk exposures by understanding the sources of these challenges: contractual obligations, pertinent regulatory responsibilities, and the modern electronic communications environment.


[Criminal dismemberment of the corpse].
In the period from 1959 to 1984 the Institute of Legal Medicine in Hamburg had to investigate 27 cases of criminal dismemberment. With regard to all legal autopsies the average frequency was about 1:500. A distinct increase of the number of cases is noticeable within the last years; i.e., 1984 there were 6 victims. Our study enclosed the autopsy findings, the police investigations, and the available court records. 11 cases were classified as defensive and 16 cases as offensive dismemberment of bodies (among these: 2 cases of dismemberment after stealing the corpse and 2 cases of killing the victims by decapitation). One perpetrator had 3 victims, twice there was a perpetrator with 2 victims. The victims were of all ages, but mainly between 40 and 50 years old. 22 of them were female and 5 male. 16 perpetrators could be identified, 14 of them were male and 2 female; all of them were older than 30 years, mostly between the age of 40 and 50. The psychiatric experts classified 11 of the perpetrators as "normal," 3 as abnormal, and 2 as psychotic. More details concerning victims, perpetrators, used instruments for killing and dismembering, elimination and identification of the dismembered bodies and judicial aspects are given in this paper.


A multicenter study of recombinant factor VIII (Recombinate) in previously treated patients with hemophilia A. The Recombinate Previously Treated Patient Study Group.
A prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treatment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII: none was serious. No patient developed an inhibitor to rFVIII.


Aquaculture-capture fisheries nexus under Covid-19: impacts, diversity, and social-ecological resilience.
The Covid-19 pandemic is a global shock that is significantly affecting coastal social-ecological systems (SES) in different parts of the world. Its widespread impacts have unravelled vulnerabilities in many aspects of society, including food systems. Our study investigated the impacts of a lockdown associated with the pandemic in the province of Bulacan, in the region of Central Luzon, Philippines, where aquaculture and capture fisheries are important and interconnected sectors. In particular, we focused on impacts related to production and market. We considered people's coping strategies and the factors that enabled such strategies. Our investigation adopted a case study approach and drew on qualitative data analysed through thematic analysis. The findings revealed differentiated mechanisms through which aquaculture and capture fisheries production were impacted. Both were strongly affected by market disruptions but through slightly different ways. In effect, the lockdown provided the impetus for the uptake and spreading of practices that were previously peripheral, particularly in relation to market exchanges. The study also identified a variety of coping strategies, as well as the importance of social support in the form of food aid, financial assistance, and institutional livelihood assistance. Finally, it discusses the importance of diversity in food sources, the role of local food systems, and governance implications for foregrounding social-ecological resilience in short-term response and long-term recovery.


Extraction and validation of a lower limb HAQ by comparison with objective measurement of ambulatory activity.
Both the Health Assessment Questionnaire (HAQ) and the measurement of spontaneous ambulatory activity are measures that can be used to evaluate disability in RA. A cross sectional survey was conducted of 105 RA patients where the HAQ was compared with ambulatory activity from the Numact monitor. Rank correlation was used to evaluate the relationships between activity and the complete and individual sections of the HAQ. Correlation of activity with total HAQ produced significant results (r= -0.29 to -0.48). Correlation with individual sections showed the strongest association with "Hygiene", followed by "Activities", and "Walking". A lower limb HAQ was devised using these and the dressing and rising items. HAQ and recorded activity measure different but related aspects of disability. Activity should be used if the ability to quantify the result outweighs the extra effort involved in the study.


CROI 2021: Metabolic and Other Complications of HIV Infection or COVID-19.
Comorbid conditions have a major impact on the health, quality of life, and survival in people with HIV, particularly as they age. The 2021 Conference on Retroviruses and Opportunistic Infections featured excellent science related to specific comorbidities as well as multimorbidity. A number of presentations related to comorbidities in women with HIV reflected a new wave of research aimed at understanding how the epidemiology and pathogenesis of comorbidities may differ by sex. Weight gain related to antiretroviral therapy was also a major theme of the comorbidity abstracts presented at the meeting. Several presentations demonstrated the importance of comorbid conditions in COVID-19 outcomes in people with HIV and described persistent symptoms after acute SARS-CoV-2 infection has resolved, a nascent topic that will expand over time. This review focuses on research presented at the conference in these areas, highlighting those with the most clinical impact.