Hatted 1T/2H-Phase MoS2 on Ni3 S2 Nanorods for Efficient Overall Water Splitting in Alkaline Media.
A new hatted 1T/2H-phase MoS2 on Ni3 S2 nanorods, as a bifunctional electrocatalyst for overall water splitting in alkaline media, is prepared through a simple one-pot hydrothermal synthesis. The hat-rod structure is composed mainly of Ni3 S2 , with 1T/2H-MoS2 adhered to the top of the growth. Aqueous ammonia plays an important role in forming the 1T-phase MoS2 by twisting the 2H-phase transition and expanding the interlayer spacing through the intercalation of NH3 /NH4 + . Owing to the special "hat-like" structure, the electrons conduct easily from Ni foam along Ni3 S2 to MoS2 , and the catalyst particles maintain sufficient contact with the electrolyte, with gaseous molecules produced by water splitting easily removed from the surface of the catalyst. Thus, the electrocatalytic performance is enhanced, with an overpotential of 73 mV, a Tafel slope of 79 mV dec-1 , and excellent stability, and the OER demonstrates an overpotential of 190 mV and Tafel slope of 166 mV dec-1 .


T cell response to the cytomegalovirus major capsid protein (UL86) is dominated by helper cells with a large polyfunctional component and diverse epitope recognition.
T cells are crucial in controlling cytomegalovirus (CMV) infection. The CMV major capsid protein (UL86) is frequently recognized by these cells, but the nature of this response has not been explored in detail. In this study, healthy CMV-exposed individuals were examined, and ex vivo peptide stimulation of peripheral blood mononuclear cells and flow-cytometry were used to obtain data, including response prevalence, magnitude, functional profiles, and recognized epitopes. Of 24 subjects, 19 (79%) had a UL86-specific CD4 T cell response rate between 0.03% and 1.4%. This group of individuals exhibited a similar percentage of polyfunctional T cells in their UL86-specific and pp65-specific responses. A total of 8 CD4 T cell epitopes were identified. In contrast, CD8 T cell responses to UL86 were rare and small. UL86 is of interest for monitoring the response to CMV.


Female sexual behavior in male rats: effect of hour of castration at birth.
In the male rat, a dramatic increase in serum testosterone occurs during the first four hours of postnatal life. The experiments sought to determine whether such an increase would participate directly on the defeminization process. Newborn male rats were castrated either at 0 hr in utero (literally at the moment of birth) or at 6 or 12 hrs after birth. Some males were castrated at 0 hr in utero and injected at the time of surgery with 1 or 5 micrograms testosterone propionate (TP). At about 90 days of age, each animal was injected with estrogen and progesterone and tested for female sex behavior. Males castrated at 0 hr in utero displayed typical female sex behavior. Males castrated at 6 or 12 hrs after birth were less receptive than males castrated at 0 hr. Males castrated at 0 hr and injected with testosterone at this time almost never showed lordosis as adults after treatment with ovarian hormones. These results are consistent with the idea that the rapid elevation in serum testosterone which occurs shortly after birth suppresses the development of sexual behavior sensitivity to ovarian hormonal stimulation.


A phase II study of topical ceramides for cutaneous breast cancer.
Short chain ceramides induce tumor cell apoptosis in preclinical models. Limited therapeutic options for patients with cutaneous breast cancer prompted the testing of these sphingolipids in patients with this disease. Twenty-five patients with refractory, cutaneous breast cancer were treated twice a day with a 1% mixture of topical C2 and C6 ceramides administered in a 1:1 ratio. For the first 8 weeks, patients were not allowed to receive other antineoplastic therapy. In addition to tumor status and toxicity assessment throughout the trial, skin biopsies for evidence of apoptosis and quality of life questionnaires (FACT-BR) were completed at baseline and 1 month. Only one patient manifested a partial response with topical ceramides, yielding a response rate of 4% (90% confidence interval 0, 17.6%). Median cutaneous progression-free survival was 2 months. The topical ceramides were also well tolerated, with no grade 3 or 4 toxicity reported. None of the six patients who underwent serial skin biopsies showed increased tumor cell apoptosis morphologically or by the modified TUNEL assay. To our knowledge, this trial is one of the first clinical investigations of short chain ceramides. This trial's results are not promising enough to merit further study of ceramides in the manner prescribed.


Proximal interphalangeal joint fractures treated with a dynamic external fixator: A multicenter and retrospective study of 88 cases.
Ligamentotaxis is now a well-established treatment method for proximal interphalangeal (PIP) joint fractures. Despite satisfactory results, the technique is considered complex and the devices cumbersome. The aim of this study was to evaluate a miniaturized dynamic external fixator (Ligamentotaxor(®)) for the management of these fractures. Eighty-six patients with 88 fractures of the PIP joint were treated at 10 European hand surgery centers. The device was applied within eight days of the injury and was removed 40-45 days after the injury. Treatment complications included superficial infection (4 cases), osteoarthritis (1 case), and localized but resolving complex regional pain syndrome (4 cases). The fracture healed in all cases. At final follow-up (mean: 15.2 months), average range of motion was 70° (range: 0-110°). Functional results were comparable between the 10 participating centers. Pain occurred upon exertion in 47% of the patients, 40% were sensitive to weather changes and 26% experienced constant pain. The mean QuickDASH score was 15.7 (range: 11-37) and 83.7% of the patients had no limitations during their daily activities. The results of this series are similar to those reported in other studies of PIP fracture treatment with external fixators. This technique is reliable and reproducible. The device is easy to handle by surgeons and well tolerated by patients. We think that this simple, reliable technique could be relevant for the management of PIP joint fractures.


Cardiovascular disease in women.
Gender-specific data focused on cardiovascular disease (CVD) are becoming increasingly available. This is of great importance, given that CVD has become the number 1 killer of women, and unlike for men, mortality rates do not seem to be declining. Many factors are cited as the causes of sex-based differences, including delays in recognizing symptoms, underutilization of diagnostic tests and treatments, as well as anatomic, physiological, and genetic factors. Evidence of fundamental biological differences in vascular function and the underlying pathologic processes is only beginning to elucidated, motivated by growing evidence of differences in clinical presentations and outcomes between men and women. The good news is that we are starting to see improvements in outcomes for women, such as after coronary revascularization; decrease in complication rates with the advent of new techniques, such as radial access for cardiac catheterizations; as well as increased participation of women in clinical trials. The underlying mechanisms of ischemic heart disease remain to be elucidated, and will help guide therapy and ultimately may explain the higher prevalence of : subendocardial myocardial infarctions, spontaneous arterial dissections, plaque erosion, increased vasospastic disorders, such as coronary microvascular disease, and pulmonary hypertension in women compared with men. We have made great progress in understanding gender-related differences in CVDs, but much remains to be done to optimize the prevention of CVD for both men and women.


Post-COVID-19 illness and associations with sex and gender.
Post-COVID-19 syndromes have associated with female sex, but the pathophysiological basis is uncertain. There are sex differences in myocardial inflammation identified using cardiac magnetic resonance (CMR) in post-COVID-19 patients, and in patient reported health outcomes following COVID-19 infection. This prospective study investigated the time-course of multiorgan injury in survivors of COVID-19 during convalescence. Clinical information, blood biomarkers, and patient reported outcome measures were prospectively acquired at enrolment (visit 1) and 28-60 days post-discharge (visit 2). Chest computed tomography (CT) and CMR were performed at visit 2. Follow-up was carried out for serious adverse events, including death and rehospitalization. Sixty-nine (43%) of 159 patients recruited were female. During the index admission, females had a lower peak C-reactive protein (74 mg/l (21,163) versus 123 mg/l (70, 192) p = 0.008) and peak ferritin (229 μg/l (103, 551) versus 514 μg/l (228, 1122) p < 0.001). Using the Modified Lake-Louise criteria, females were more likely to have definite evidence of myocardial inflammation (54% (37/68) versus 33% (30/90) p = 0.003). At enrolment and 28-60 days post-discharge, enhanced illness perception, higher levels of anxiety and depression and lower predicted maximal oxygen utilization occurred more commonly in women. The mean (SD, range) duration of follow-up after hospital discharge was 450 (88) days (range 290, 627 days). Compared to men, women had lower rates of cardiovascular hospitalization (0% versus 8% (7/90); p = 0.018). Women demonstrated worse patient reported outcome measures at index admission and 28-60 days follow-up though cardiovascular hospitalization was lower.


Factors associated with the length of stay in total knee arthroplasty patients with the enhanced recovery after surgery model.
The purpose of this study is to identify the factors that influence the length of stay (LOS) in total knee arthroplasty (TKA) patients with an enhanced recovery after surgery (ERAS) program. Information from 167 patients (31 males and 136 females, range from 43 years to 88 years old) who underwent the unilateral elective primary TKA from January 2017 to January 2019 were reviewed retrospectively. Factors were analyzed by single-factor variance and multi-factor linear regression. By single-factor variance analysis, American Society of Anesthesiologists (ASA) physical status classification system, pre-operation albumin, pre-operation erythrocyte sedimentation rate (ESR), primary and merge diseases, hidden blood loss, and length of operation were correlated with LOS (P < 0.05). Multi-factor linear regression results suggested that gender, ASA class, pre-operation Alb, and pre-operation ESR were associated with LOS (P < 0.05). Moreover, ASA class 3 (B value 4.84), pre-operation Alb < 30 g/L (B value 18.33), and pre-operation ESR > 15 mmol/h (B value 2.21) could increase the LOS, while males (B value - 3.56) had a shortened LOS. Overall, our research found that female, ASA class 3, pre-operation Alb < 30 g/L, and pre-operation ESR > 15 mmol/h could extend LOS in TKA patients with ERAS.


Outcomes of spontaneous bacterial peritonitis in liver transplant recipients with allograft failure.
Spontaneous bacterial peritonitis (SBP) carries appreciable morbidity and mortality in the pre-liver transplant (LT) setting. However, the occurrence of SBP and its consequences in the post-LT setting have not been well characterized. This is a retrospective study of SBP occurring in post-LT patients between January 2007 and December 2012. Outcomes were compared to a cohort of post-LT patients with allograft failure and ascites without SBP. The most common indication for liver transplantation in this cohort was hepatitis C. A total of 29 episodes of SBP in 21 patients were identified. Escherichia coli (19%) and Klebsiella pneumoniae (10%) were the most frequent pathogens identified. Six patients died during their first episode of SBP. Ten patients were eventually listed for liver re-transplantation (re-LT) after their first episode of SBP; 5 of these patients were transplanted and the other 5 died. Of the 5 who were transplanted, 2 died shortly after re-transplant, and 3 are still alive. The cause of death in the majority of patients was infection (83.3%). The median time from onset of ascites to death was 214 days (range: 10-1085 days) and from the first episode of SBP to death was 50.5 days (range: 4-549 days). In contrast, the median time from onset of ascites to death in patients with allograft failure and ascites without SBP was 331.5 days (45-2400 days). Allograft failure with ascites is a poor prognostic factor and these patients should be considered high risk for re-LT. SBP may accelerate the time to mortality.


The relationship between dietary antioxidant intake and physical activity rate with nonalcoholic fatty liver disease (NAFLD): A case - Control study.
Although dietary intakes, especially micronutrients, can be associated with the severity of nonalcoholic fatty liver disease (NAFLD), investigations on the amount of vitamins and antioxidants consumption and their relationship with NAFLD are very limited and incomplete. Therefore, we decided to investigate the relationship between antioxidant compounds intake and physical activity rate with NAFLD. In this study, 200 patients with NAFLD for the case group and 400 healthy subjects for the control group were selected. Patients were diagnosed as NAFLD after giving blood tests and performing Ultrasonography by a radiology specialist. Dietary intakes were evaluated through a validated 168-items semi-quantitative food frequency questionnaire (FFQ). Physical activity rate was estimated by a validated short form of International Physical Activity Questionnaire (Short IPAQ). The study population was between 20 and 60 years old and 46% of them were women. Weight, waist circumference, hip circumference, WHR, and BMI in the cases were higher than the controls. Physical activity comparisons showed that controls had higher physical activity rate than cases. Mean consumption of vitamins C, A, D and alpha-tocopherol in case group was less than the other group. After adjustment for all potential confounder, subjects who were in highest tertile of vitamin A intake -in comparison to those in the lowest tertile of intake-decreased risk of NAFLD (OR = 0.40, 95%CI: 0.30-0.55). The same finding was obtained for vitamin D; [Top category vs. bottom category of vitamin D of intake (OR = 0.35, 95%CI: 0.20-0.61)]. We found that more intakes of vitamins A and D are related to lower risk of NAFLD in this group of Iranian adults. Physical activity rate in cases was less than the controls. Further prospective studies are required to confirm causal association between antioxidant compounds intake and NAFLD.


Simultaneous determination of nicotinamide and N1 -methylnicotinamide in human serum by LC-MS/MS to associate their serum concentrations with obesity.
A rapid and sensitive LC-MS/MS method was developed and validated for the simultaneous determination of nicotinamide and its metabolite N1 -methylnicotinamide in human serum. Serum samples were prepared by protein precipitation with acetonitrile. The chromatographic separation was performed on a Waters Spherisorb S5 CN microbore column (2.0 × 100 mm, 5 μm) with gradient elution within 7 min. Acetonitrile and 5 mm ammonium formate aqueous solution (containing 0.1% formic acid) were used as mobile phases. Nicotinamide, N1 -methylnicotinamide and N'-methylnicotinamide (internal standard) were detected with a triple-quadrupole tandem mass spectrometer in the positive ion mode. Multiple reaction monitoring was used to monitor precursor to product ion transitions of m/z 123.1 → 80.1 for nicotinamide, m/z 137.1 → 94.1 for N1 -methylnicotinamide and m/z 137.1 → 80.1 for the internal standard. The linear ranges of nicotinamide and N1 -methylnicotinamide were 5.000-160.0 and 2.500-80.00 ng/ml, respectively. The intra- and inter-day precisions (RSD) of both analytes were within 6.90%. The recoveries were >88%. The analytes were proven to be stable during all sample storage, preparation and analytic procedures. The method was successfully applied to determine the concentrations of nicotinamide and N1 -methylnicotinamide in human serum to investigate the association between their concentrations and obesity in 1160 Chinese subjects.


Isolation and characterization of two novel root-specific promoters in rice (Oryza sativa L.).
Novel root-specific promoters are important for developing methods to drive root-specific gene expression for nutrient and water absorption. RT-PCR (reverse transcription polymerase chain reaction) analysis identified high expression levels of Os03g01700 and Os02g37190 in root tissues across developmental stages in comparison with the constitutive genes OsAct1 (rice Actin1 gene), OsUbi1 (rice polyubiquitin rubi1 gene), and OsCc1 (rice cytochrome c gene). The copy numbers of Os03g01700 and Os02g37190 were evaluated by qRT-PCR. The results showed that Os03g01700 and Os02g37190 transcripts were highly accumulated in the examined root tissues but were not detected in young embryos or leaves at the indicated days after germination or in the panicle, in contrast to the ubiquitous expression of OsAct1, OsUbi1, and OsCc1. Additionally, the promoter regions of these two genes were linked to the GUSplus reporter gene and transformed into rice. GUS staining of the transgenic plants showed that the Os03g01700 and Os02g37190 promoters were active in primary and secondary roots throughout the developmental stages, except in root hairs. The GUSPlus transcript levels were also highly root-specific in the transgenic rice. Overall, the two promoters are highly active in the root tissues of rice and can be useful for the root-specific enhancement of target gene(s).


Engineered antibody fusion proteins for targeted disease therapy.
Since the FDA approval of the first therapeutic antibody 35 years ago, antibody-based products have gained prominence in the pharmaceutical market. Building on the early successes of monoclonal antibodies, more recent efforts have capitalized on the exquisite specificity and/or favorable pharmacokinetic properties of antibodies by developing fusion proteins that enable targeted delivery of therapeutic payloads which are otherwise ineffective when administered systemically. This review focuses on recent engineering and translational advances for therapeutics that genetically fuse antibodies to disease-relevant payloads, including cytokines, toxins, enzymes, neuroprotective agents, and soluble factor traps. With numerous antibody fusion proteins in the clinic and other innovative molecules poised to follow suit, these potent, multifunctional drug candidates promise to be a major player in the therapeutic development landscape for years to come.


Malaria elimination in Malaysia and the rising threat of Plasmodium knowlesi.
Malaria is a major public-health problem, with over 40% of the world's population (more than 3.3 billion people) at risk from the disease. Malaysia has committed to eliminate indigenous human malaria transmission by 2020. The objective of this descriptive study is to understand the epidemiology of malaria in Malaysia from 2000 through 2018 and to highlight the threat posed by zoonotic malaria to the National Malaria Elimination Strategic Plan. Malaria is a notifiable infection in Malaysia. The data used in this study were extracted from the Disease Control Division, Ministry of Health Malaysia, contributed by the hospitals and health clinics throughout Malaysia. The population data used in this study was extracted from the Department of Statistics Malaysia. Data analyses were performed using Microsoft Excel. Data used for mapping are available at EPSG:4326 WGS84 CRS (Coordinate Reference System). Shapefile was obtained from igismap. Mapping and plotting of the map were performed using QGIS. Between 2000 and 2007, human malaria contributed 100% of reported malaria and 18-46 deaths per year in Malaysia. Between 2008 and 2017, indigenous malaria cases decreased from 6071 to 85 (98.6% reduction), while during the same period, zoonotic Plasmodium knowlesi cases increased from 376 to 3614 cases (an 861% increase). The year 2018 marked the first year that Malaysia did not report any indigenous cases of malaria caused by human malaria parasites. However, there was an increasing trend of P. knowlesi cases, with a total of 4131 cases reported in that year. Although the increased incidence of P. knowlesi cases can be attributed to various factors including improved diagnostic capacity, reduction in human malaria cases, and increase in awareness of P. knowlesi, more than 50% of P. knowlesi cases were associated with agriculture and plantation activities, with a large remainder proportion linked to forest-related activities. Malaysia has entered the elimination phase of malaria control. Zoonotic malaria, however, is increasing exponentially and becoming a significant public health problem. Improved inter-sectoral collaboration is required in order to develop a more integrated effort to control zoonotic malaria. Local political commitment and the provision of technical support from the World Health Organization will help to create focused and concerted efforts towards ensuring the success of the National Malaria Elimination Strategic Plan.


Thalassemia syndromes. Recent advances.
Laboratory and clinical investigators in the past several years have provided many advancements in the understanding of the thalassemia syndromes and in the care of affected patients. The diversity of genetic defects causing thalassemia has been extensively explored, with major benefits to our knowledge of normal globin gene function and of the consequences of specific mutations. In addition, the use of molecular biology methods in these studies has provided major advances in population genetics, gene transfer, and prenatal diagnosis of thalassemia. In the clinical area, guidelines for transfusion, splenectomy, prevention of postsplenectomy infection, and effective iron chelation have been considerably improved, and bone marrow transplantation is now available as an alternative means of treatment. Despite these advances, a great deal remains to be done in the areas of understanding the developmental regulation of globin gene expression, effective gene transfer, oral chelation therapy, safer blood products, and other important areas that will benefit patients afflicted with thalassemia.


Assessing non-specific symptoms in epidemiological studies: Development and validation of the Symptoms and Perceptions (SaP) questionnaire.
To describe the development of the Symptoms and Perceptions (SaP) questionnaire, a new instrument measuring diversity and severity features and related perceptions of non-specific (physical and psychological) symptoms (NSS) and to test its reliability and validity within an epidemiological setting. First, a Delphi study was performed to develop the items of the questionnaire. Its psychometric properties were then tested within the context of an epidemiological study. This study yielded questionnaire data and general practice registry data from a sample of 5933 Dutch adults. Principal component analyses (PCA) were performed to test the factorial structure of the symptom assessment subscales of the SaP. Indicators of reliability and convergent validity were examined separately for the questionnaire parts of symptoms and perceptions. Criterion validity of the symptom scores of the SaP was also explored. The factorial structure of the symptom subscales reflected meaningful sets of clusters, indicative of the representation of all relevant organ systems. The SaP showed high reliability and good convergent validity for both the symptoms and perceptions part. It was also able to identify, to a certain degree, cases of diagnosed somatoform disorders and multiple NSS in primary care. Additionally, the scores on the "psychological" factor fairly predicted the diagnosis of common mental disorders. The SaP questionnaire is a reliable and valid self-reported measure of diverse features of NSS and corresponding perceptions. It can also be a useful tool for the identification of multiple somatic symptoms and related disorders in general practice and assessment of psychological problems in epidemiological studies. Further validation of the questionnaire in different samples and settings will establish the promising psychometric properties demonstrated in the present study.


A 3D origami multiple electrochemiluminescence immunodevice based on a porous silver-paper electrode and multi-labeled nanoporous gold-carbon spheres.
A simple and sensitive 3D origami multiple electrochemiluminescence immunodevice based on a novel silver nanoparticles modified porous paper working electrode as a sensor platform and multi-labeled nanoporous gold-carbon spheres as tracers has been demonstrated for the first time.


Histamine.
Histamine is a potent mediator of immediate hypersensitivity reactions, and is stored primarily in mast cells and basophils. It exerts its pharmacologic effects through interactions with H1 and H2 cell surface receptors, which promote changes in vascular permeability, levels of cyclic nucleotides, neutrophil and eosinophil chemokinesis and chemotaxis, gastrointestinal secretion, and smooth muscle contraction. H1 and H2 antihistamines have been utilized to interfere with these responses and have proven clinically useful in the treatment of some types of rhinoconjunctivitis, urticaria, and peptic ulcer disease. Several types of biochemical assays have been developed to assess histamine release from mast cells and basophils as well as to measure blood, urine, and tissue levels of histamine. The guinea pig ileum bioassay, fluorometric assay, and radioenzyme assay, each with certain modifications and limitations, have provided useful information concerning the function of histamine in health and disease.


Enhanced or Weakened Western North Pacific Subtropical High under Global Warming?
The Western North Pacific Subtropical High (WNPSH) regulates East Asian climate in summer. Anomalous WNPSH causes floods, droughts and heat waves in China, Japan and Korea. The potential change of the WNPSH under global warming is concerned by Asian people, but whether the WNPSH would be enhanced or weakened remains inconclusive. Based on the multi-model climate change projection from the 5th phase of Coupled Model Intercomparison Project (CMIP5), we show evidences that the WNPSH tends to weaken and retreat eastward in the mid-troposphere in response to global warming, accompanied by an eastward expansion of East Asian rain belt along the northwestern flank of WNPSH. Weakened meridional temperature gradient on the northern flank of WNPSH and the associated thermal wind account for the weakened WNPSH in the mid troposphere. We recommend the WNPSH be measured by eddy geopotential height (He) instead of traditionally used geopotential height, especially in climate change studies.


Enhanced hydrogen evolution reaction in alkaline solution by constructing strong metal-support interaction on Pd-CeO2-x-NC hybrids.
Diminishing the size of metal nanostructures can significantly improve the performance of catalysts. However, the self-aggregation of small particles is still an insurmountable obstacle, resulting in the unfavorable stability and recyclability. Herein, we designed and fabricated the Pd-CeO2-x-NC catalyst though an accurate deposition strategy to downsize the Pd particle to sub-nanometer level and enhance its running stability. The CeO2-x nanoclusters were firstly dispersed on the nitrogen-doped carbon nanosheets. Further, the active Pd sub-nanoclusters were accurately scattered on the surface of CeO2-x ascribing to the strong metal-support interaction (SMSI) between Pd and CeO2-x, which was beneficial to promote the catalytic activity. Subsequently, the high oxidation state Pdn+ species were formed due to the electron transfer from Pd to CeO2-x caused by the SMSI effect. Strikingly, the HER performance of Pd-CeO2-x-NC was surprisingly correlated with the ratio of Pdn+, suggesting Pdn+ acted as the dominant active species. Besides, the SMSI effect stabilized the valence state of active Pdn+ species and prevented the sub-nanometer Pd clusters from aggregation, which played a vital role for the enhanced stability of the hybrid catalyst. This synthetic process described here is contributed to prepare various nanostructured catalysts with satisfactory stability through the direct targeting strategy.


A comparison of freezer-stored DNA and herbarium tissue samples for chloroplast assembly and genome skimming.
The use of DNA from herbarium specimens is an increasingly important source for evolutionary studies in plant biology, particularly in cases where species are rare or difficult to obtain. Here we compare the utility of DNA from herbarium tissues to their freezer-stored DNA counterparts via the Hawaiian Plant DNA Library. Plants collected for the Hawaiian Plant DNA Library were simultaneously accessioned as herbarium specimens at the time of collection, from 1994-2019. Paired samples were sequenced using short-read sequencing and assessed for chloroplast assembly and nuclear gene recovery. Herbarium specimen-derived DNA was statistically more fragmented than freezer-stored DNA derived from fresh tissue, leading to poorer chloroplast assembly and overall lower coverage. The number of nuclear targets recovered varied mostly by total sequencing reads per library and age of specimen, but not by storage method (herbarium or long-term freezer). Although there was evidence of DNA damage in the samples, there was no evidence that it was related to the length of time in storage, whether frozen or as herbarium specimens. DNA extracted from herbarium tissues will continue to be invaluable, despite being highly fragmented and degraded. Rare floras would benefit from both traditional herbarium storage methods and extracted DNA freezer banks.


The emerging role of mass spectrometry-based proteomics in molecular pharming practices.
Molecular pharming relies on the integration of foreign genes into a plant system for production of the desired recombinant protein. The speed, scalability, and lack of contaminating human pathogens highlights plants as an enticing and feasible system to produce diverse protein-based products, including vaccines, antibodies, and enzymes. However, limitations of expression levels, host defense responses, and production irregularities underscore distinct areas for improvement within the molecular pharming pipeline. Within the past five years, mass spectrometry-based proteomics has begun to address these critical areas and show promise in advancing our understanding of the complex biological systems driving molecular pharming. Further, opportunities to leverage comprehensive proteome profiling have surfaced to meet good manufacturing practice regulations and move biopharmaceuticals derived from plants into mainstream production.


Infection-Induced Porcine Ex Vivo Corneal Wound Model to Study the Efficacy of Herpes Simplex Virus-1 Entry and Replication Inhibitors.
Corneal infections by viruses and bacteria can result in ocular surface defects, ulcers, or wounds. Herpes simplex virus type-1 (HSV-1) is a human virus with global seroprevalence in the range of 60-90%. While the virus more commonly causes mucocutaneous lesions including ulcers on the face and mouth, it is also a leading cause of infection-associated blindness. In this chapter, we discuss an in-depth protocol required to evaluate corneal damage due to HSV-1 infection using porcine models of ex vivo infection. Our methods can be adapted to study similar infections caused by other viruses and bacteria.


CCK receptors in release of pancreatic polypeptide (PP) in dogs.
Pancreatic polypeptide (PP) is released after ingestion of protein-fat meals and following administration of some gut hormones (CCK and bombesin), but the hormonal contribution to the physiological release of PP has not been elucidated. We used specific and potent CCK-receptor antagonist, L-364,718, administered intravenously in a dose of 0.5 mumol/kg or intraduodenally in a dose of 2 mumol/kg to assess the role of CCK in the release of PP. Exogenous CCK-8 infused intravenously in gradually increasing doses (12.5-400 pmol/kg/hr) caused a dose-dependent increase in plasma PP from basal 28 +/- 4 pM to 136 +/- 18 pM, and this PP increase was completely suppressed by both intravenous and intraduodenal administration of L-364,718. Meat feeding caused a dramatic increase in plasma PP from a basal level of 26 +/- 4 pM to a peak of about 190 +/- 32 pM, and the pretreatment with intravenous or intraduodenal L-364,718 reduced this PP increase by about 60%. Duodenal perfusion with oleate (0.12-4.0 mmol/hr) or L-Trp (0.12-4.0 mmol/hr) also increased plasma PP, reaching, respectively, 180 +/- 28 pM and 76 +/- 6 pM. Pretreatment with intravenous or intraduodenal L-364,718 completely abolished the plasma PP responses to oleate and L-Trp. Bombesin (100 pmol/kg/hr) raised plasma PP to the level similar to that achieved by meat feeding and L-364,718 given intravenously or intraduodenally blocked completely these plasma PP increments.(ABSTRACT TRUNCATED AT 250 WORDS)


[The role of hemostasis and rheologic properties of blood in stable and progressive exertion-induced stenocardia].
Patients with angina of effort, both its stable and progressive variants, show hypercoagulative hemostatic shifts and a deterioration of blood rheologic properties, the changes being more pronounced in progressive angina. Vascular-wall changes, dependent on the level of plasma Willebrand's factor, are closely related to clinical severity of angina of effort. The latter is also related to changes in blood rheology (increased erythrocyte aggregation, reduced erythrocyte deformation and high platelet adhesion).


Assessing the severity of functional impairment of psychiatric disorders: equipercentile linking the mini-ICF-APP and CGI.
The assessment of functioning and impairment due to psychiatric illness has been acknowledged to be crucial for research and practice. This led to the development of the mini-ICF-APP, which provides a reliable and time-efficient measure of functioning and impairment. Although its use is increasing, it remains unclear how it reflects severity and how change might be interpreted from a clinical perspective. In a clinical sample of 3067 individuals hospitalized for mental health treatment, we used an equipercentile approach to link the mini-ICF-APP with the Clinical Global Impression scale (CGI) at admission and discharge. We linked the mini-ICF-APP sum score to the CGI-S scale and the mini-ICF-APP proportional change between admission and discharge to the CGI-I scale. The mini-ICF-APP and CGI scales showed a Spearman correlation of 0.50 (p < .000). CGI-S: "borderline-ill" corresponded to a mini-ICF-APP score 1-2; "mildly-ill" to 3-7; "moderately-ill" to 8-15; "markedly-ill" to 16-24; "severely-ill" to 25-37; and "extremely-ill" to a score ≥ 38. The Spearman correlation between the percentage change of mini-ICF-APP sum score and the CGI-I was 0.32 (p > .000); "no-change" in the CGI-I corresponded to an increase or decrease of 2%; "minimally-improved" to a mini-ICF-APP reduction of 3-30%; "much-improved" to a reduction of 31-63%; "very-much-improved" to a reduction of ≥64% "minimally-worse" to an increase of 3-34% "much-worse" to an increase of 35-67%; and finally "very-much-worse" with an increase of ≥68%. Our findings improve understanding of the clinical meaning of the mini-ICF-APP sum score and percentage change in patients hospitalized for treatment.


Survey of bed bug infestations in homeless shelters in southern France.
Bed bug has become a major public health pest worldwide. Infestation may result in numerous negative health effects. Homeless shelters are one of the most habitats that can be infested with bed bugs, a few studies have focused on bed bug infestations in these settings. We conducted a survey of infestations of bed bugs in a homeless shelter in southern France, using an innovative seven-level scale (0-6) to assess the degree of infestation, MALDI TOF-MS to identify bed bugs, and a biomolecular tool to detect bacteria. Bed bug infestations were documented in 13% (9/68) of investigated rooms. A total of 184 bed bugs were collected and morphologically identified as Cimex lectularius. MALDI TOF-MS analysis allowed us to obtain high-quality MS spectra for all 184 specimens, to correctly identify all specimens, and included 178/184 (97%) Log Score Values higher than 1.8. Among the bacteria tested, Wolbachia sp. DNA was found in 149/184 (81%) of the bed bugs, and one sample was positive for Coxiella burnetii, the agent of Q fever. Our study is the first of its kind that offers new perspectives for increasing public awareness of the conditions in homeless shelters.


MYC overexpression but not MYC/BCL2 double expression predicts survival in bulky mass diffuse large B-cell lymphoma patients.
The prognostic factors for diffuse large B-cell lymphoma (DLBCL) have been fully explored, but prognostic information for bulky mass DLBCL patients is limited. This study aimed to analyze the prognostic value of MYC protein expression and other biological parameters in bulky mass DLBCL patients. We defined a bulky mass as a maximum tumor diameter ≥7.5 cm and studied 227 patients with de novo bulky mass DLBCL. In all patients with bulky mass DLBCL, the 1-year and 3-year OS rates were 72.7% and 57.1%, respectively, and the 1-year and 3-year PFS rates were 52.0% and 42.5%, respectively. The MYC overexpression group (n = 140) showed significantly worse overall survival (OS; p = 0.019) and progression-free survival (PFS; p = 0.001) than the non-MYC overexpression group (n = 87). Subgroup analyses demonstrated that the MYC overexpression group was associated with inferior OS and PFS in the subgroups with the International Prognostic Index score of 3-5 (OS: p = 0.011; PFS: p < 0.001), Ann Arbor stage 3-4 (OS: p = 0.014; PFS: p < 0.001) and GCB subtype (OS: p = 0.014; PFS: p = 0.010). Consolidation radiotherapy improved OS and PFS in patients with bulky mass DLBCL (OS: p = 0.008; PFS: p = 0.004) as well as in those with MYC overexpression (OS: p = 0.001; PFS: p = 0.001). The prognostic value of MYC overexpression was maintained in a multivariate model adjusted for the International Prognostic Index. MYC overexpression is a poor predictor for bulky mass DLBCL patients. Consolidation radiotherapy for residual disease after induction therapy may improve outcomes for patients with bulky mass DLBCL.


A computational tool to optimize ligand selectivity between two similar biomacromolecular targets.
Algorithms for a new computer program designed to increase ligand-receptor selectivity between two proteins are described. In this program ligand-receptor selectivity is increased by functional modifications to the ligand so as to increase the calculated binding affinity of it to one protein and/or decrease the calculated binding affinity of it to the other protein. The structure of the ligand is modified by selective replacement of atoms and/or functional groups in silico based on a specific set of steric and/or hydropathic complementarity rules involving atoms and functional groups. Relative binding scores are calculated with simple grid-based steric penalty, hydrogen bond complementarity, and with the HINT score model. Two examples are shown. First, modifying the structure of the ligand CB3717 is illustrated in a number of ways such that the binding selectivity to wild type L. casei thymidylate synthase or its E60Q mutant may be improved. Second, starting with a non-selective lead compound that had been co-crystallized with both plant and mammalian 4-hydroxyphenylpyruvate dioxygenases, new compounds (similar to selective ligands discovered by screening) to improve the selectivity of (herbicidal) inhibitors for the plant enzyme were designed by the program.


Evaluation of the risk of infection through exposure to aerosols and spatters in dentistry.
Many dental procedures produce extensive aerosols and splatters that are routinely contaminated with microorganisms. Air containing blood-bearing aerosols and surfaces contaminated by sedimenting blood particulate was sampled in 5 different dental cubicles. To assess contamination by blood particulate, the concentration of hemoglobin (Hb) in the air and on the sedimentation surfaces was determined. The mean concentration of Hb in the air aspirated in the 5 cubicles was 0.14 +/- 0.23 microg/m(3), corresponding to a blood volume of 8.7 x 10(-4) microL/m(3). Similarly, the mean concentration of blood particulate sedimented on surfaces was calculated and found to be 1.56 microL/m(2). In 80% of the cubicles monitored, 100% positivity to the Hb determination test was recorded in all of the surface samples. The results obtained revealed contamination of both air and surfaces by blood particulate. Moreover, with the exception of those obtained in 1 cubicle, all of the samples of sedimenting particulate analyzed were positive for the presence of Hb.


Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene.
New chiral regioisomeric γ-hydroxyphosphine ligands were synthesized from α-pinene. The key transformation was the thermal [2,3]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively through a hydroboration-oxidation reaction proceeding from the less hindered site providing a trans relationship between the hydroxy and the phosphine substituents.


The all-in-one nutrient solution in parenteral nutrition.
Dextrose, lipid emulsion, amino-acids, electrolytes, vitamins and trace elements were mixed in a well defined order to prepare 10 different total nutrient admixture solutions. The pH and osmolality of these solutions did not change significantly during 14 days of storage at 4 degrees C. Mean diameters of lipid particles on different occasions for the different solutions varied from 0.31 +/- 0.10 mum to 0.48 +/- 19 mum with 95% of particles less than 0.6 mum. Particles greater than 6 mum were not observed. Cultures were all negative. 243 patients received 5101 infusions of the admixture fluids. Patients on treatment for more than 1 week showed improved nitrogen balance. Serum transferrin and albumin were increased when treatment was ongoing for more than 2 weeks. No adverse reactions or abnormal laboratory findings were observed. One patient, with only duodenum and a part the colon left, has been maintained in good health for more than 55 months using this kind of nutritional support.


Preorganized AgI Bimetallic Precursor with Labile Diphosphorus Ligands for a Programmed Synthesis of Organometallic-Organic Hybrid Polymers.
An AgI dimer capped with labile organometallic diphosphorus ligands [Cp2 Mo2 (CO)4 (η2 -P2 )] (Cp=C5 H5 ) acts as a highly pre-organized molecular precursor to direct the construction of 1D or 2D, and 3D organometallic-organic hybrid coordination polymers upon reaction with ditopic pyridine-based linkers. The formation of the supramolecular aggregates can be controlled by the stoichiometry of the organic molecules, and the mechanism is supported by DFT calculations.


Right Ventricular Global Longitudinal Strain and Short-Term Prognosis in Patients With First Acute Myocardial Infarction.
Right ventricular (RV) dysfunction after acute myocardial infarction (AMI) is a recognized predictor of dismal prognosis. However, the most reliable RV index to predict mortality early after revascularization remains undetermined. This study aimed to explore the ability of RV global longitudinal strain (GLS) to predict inhospital mortality in patients with first AMI. All consecutive patients with first AMI were prospectively enrolled from March 2022 until February 2023. An echocardiogram was performed 24 hours after successful revascularization and RV GLS alongside conventional echocardiographic indexes were measured. Inhospital mortality was recorded. A total of 300 patients (age 61.2 ± 11.8 years, 74% male) were included in the study. RV GLS was the only RV performance index that differed significantly between anterior and inferior ST-segment-elevation patients with AMI (14.5 ± 5.2% vs 17.4 ± 5.1% respectively, p <0.001). After revascularization, 23 patients (7.7%) died in hospital. The model of Global Registry of Acute Coronary Event risk score and left ventricular ejection fraction, built for predicting inhospital mortality, significantly improved its prognostic performance only by the addition of RV GLS (chi-square value increase by 7.485, p = 0.006) compared with the other RV function indexes. RV GLS was independently associated with inhospital mortality (odds ratio 0.83, 95% confidence interval 0.71 to 0.97, p = 0.017) after adjustment for Global Registry of Acute Coronary Event risk score and left ventricular ejection fraction. Echocardiographic RV GLS measured 24 hours after revascularization in patients with first AMI outperformed conventional RV function indexes in predicting inhospital mortality.


In vitro hemocyte phagocytosis activation after experimental infection of common octopus, Octopus vulgaris (Cuvier, 1797) with Photobacterium damselae subsp. piscicida or Vibrio alginolyticus at different temperatures and infection routes.
Due to the fast growth rate, the short life cycle, the high market price and the high food conversion efficiency, O. vulgaris is considered as a good candidate for aquaculture. One of the prerequisites for the successful integration of new species, such as octopi, into industrial-scale production, is the knowledge of the pathological conditions that may arise, with emphasis on infectious diseases caused by microorganisms and para-sites transmitted through wild populations, especially for the farmed organisms cul-tured in cages in proximity to teleost fish. The main objectives of this study were to investigate the sensitivity of common octopus to experimental infection with pathogenic bacteria, to assess the activation of hemocytes and more specifically their phagocytic activity after infection and to associate sensitivity of the species and phagocytic activity of hemocytes to temperature changes, route of infection and pathogen. Common octopus individuals were intramuscularly and intravenously infected with either Photobacterium damselae subsp. piscicida or Vibrio alginolyticus. The hemocyte phagocytosis activation in vitro at two temperatures (21 ± 0.5 °C and 24 ± 0.5 °C) was studied, in an effort to relate these aspects to climate change. Hemolymph was withdrawn on days 0, 3 and 7 post infections/injections. Number of circulating hemocytes/ml hemolymph, phagocytosis ability and Phagocytosis Particle Binding Intensity index were determined. Correlations between hemocytes and bodyweight and between hemocytes and phagocytosis ability were also determined. No mortalities were recorded irrespective of pathogen, route of infection and temperature employed. Circulating hemocytes in control specimens ranged between 1.60x105 hemocytes ml-1 hemolymph to 20.02x105 hemocytes/ml hemolymph at both experiments and temperatures. The interrelation between octopi weight and circulating hemocytes showed that natural fluctuations, age, maturity stage and temperature may affect this relationship. Rise of temperature influenced phagocytosis which seemed to be route of infection, time-point and pathogen related. Specimens infected with Photobacterium damselae subsp. piscicida showed decreased phagocytosis with rise of temperature while when Vibrio alginolyticus was used, phagocytosis activity increased, in most cases. Temperature also played an important role in the correlation between the circulating hemocytes and phagocytosis activity, as at lower temperatures a negative strong correlation was observed. The results prompted us to calculate the activation index. This index showed that temperature is an important factor in hemocyte activation since for Photobacterium damselae subsp. piscicida infected specimens, hemocytes were more activated at 21 ± 0.5℃ instead of 24 ± 0.5℃, and the opposite observed for Vibrio alginolyticus samples and only later post-infection. Comparing the phagocytosis ability results with those obtained from Particle Binding Intensity index important differences concerned mainly confidence levels. The use of phagocytosis ability instead of PBI index provides more accurate results.


Patients with cardiac implantable electronic devices undergoing radiotherapy in Poland. Expert opinion of the Heart Rhythm Section of the Polish Cardiac Society and the Polish Society of Radiation Oncology.
Older age and high morbidity of the society contribute to a growing number of patients with cardiac implantable electronic devices (CIEDs) requiring effective cancer treatment, including radiotherapy (RT). The effect of RT on a CIED may vary depending on the type and physical parameters of radiation, location of the treated lesion, indications for electrotherapy, and the type of CIED. In the most dramatic scenarios, it may cause an irreversible damage to the CIED, with serious clinical consequences. The lack of precise guidelines may limit the access to RT for many patients with CIEDs who would otherwise benefit from the therapy or may lead to a therapy without taking the necessary precautions, which may worsen the prognosis. Therefore, clear and unequivocal recommendations for assessing patient eligibility for RT are aimed at ensuring that adequate precautions are taken as well as at providing patients with concomitant cardiovascular and oncologic diseases with access to safe and effective RT.


Incremental value of ABI and CAC beyond traditional risk markers in long-term prediction of cardiovascular disease incidence in participants with diabetes and impaired fasting glucose: Multi-Ethnic Study of Atherosclerosis.
Subclinical atherosclerosis (SA) diagnosis is key to primary prevention of atherosclerotic cardiovascular disease (ASCVD). SA is common among diabetics. Ankle brachial index (ABI) and coronary artery calcium (CAC) are markers of SA. This study examined whether adding ABI and CAC to diabetic individuals improved ASCVD risk prediction beyond established risk factors. MESA is an observational cohort of 6814 participants without clinical cardiovascular disease. All participants with diabetes and impaired fasting glucose were included in the analysis. The association between CAC, ABI, and incident ASCVD, and all-cause mortality was examined using Cox proportional hazard regression. The risk prediction models including ABI and/or CAC in addition to standard risk factors alone were compared. Of the 1719 participants, 55% were male and average age was 64 (±9.6) years old. Participants with diabetes or impaired fasting glucose with higher CAC and lower ABI had higher ASCVD and all-cause mortality. ABI and CAC enhanced ASCVD discrimination over standard risk factors, with C-index (95% CI) of 0.689 (0.66, 0.718) for risk factors alone, 0.696 (0.668, 0.724) for ABI, 0.719 (0.691, 0.747) for CAC, and 0.721 (0.693, 0.749) for CAC + ABI. Similarly, for all-cause mortality, both CAC and ABI improved risk discrimination in addition to standard risk factors alone. In a large population-based study of individuals with diabetes or impaired fasting glucose, the addition of ABI and CAC to conventional risk factors improved 10-year ASCVD risk prediction. ABI and CAC are non-invasive and cost-effective tests; therefore, these markers should be included into ASCVD risk stratification for primary prevention in the diabetic and impaired fasting glucose population.


Human gamma-delta (γδ) T cell therapy for glioblastoma: A novel alternative to overcome challenges of adoptive immune cell therapy.
Glioblastoma is the most common brain malignancy with devastating prognosis. Numerous clinical trials using various target therapeutic agents have failed and recent clinical trials using check point inhibitors also failed to provide survival benefits for glioblastoma patients. Adoptive T cell transfer is suggested as a novel therapeutic approach that has exhibited promise in preliminary clinical studies. However, the clinical outcomes are inconsistent, and there are several limitations of current adoptive T cell transfer strategies for glioblastoma treatment. As an alternative cell therapy, gamma-delta (γδ) T cells have been recently introduced for several cancers including glioblastoma. Since the leading role of γδ T cells is immune surveillance by recognizing a broad range of ligands including stress molecules, phosphoantigens, or lipid antigens, recent studies have suggested the potential benefits of γδ T cell transfer against glioblastomas. However, γδ T cells, as a small subset (1-5%) of T cells in human peripheral blood, are relatively unknown compared to conventional alpha-beta (αβ) T cells. In this context, our study introduced γδ T cells as an alternative and novel option to overcome several challenges regarding immune cell therapy in glioblastoma treatment. We described the unique characteristics and advantages of γδ T cells compared to conventional αβ T cells and summarize several recent preclinical studies using human gamma-delta T cell therapy for glioblastomas. Finally, we suggested future direction of human γδ T cell therapy for glioblastomas.


Optimization of gradient profiles in ion-exchange chromatography using computer simulation programs.
Optimization procedure of gradient separations in ion-exchange chromatography using simplex optimization method in combination with the computer simulation program for ion-exchange chromatography is presented. The optimization of parameters describing gradient profile for the separation in ion chromatography is based on the optimization criterion obtained from calculated chromatograms. The optimization criterion depends on the parameters used for calculations and thus exhibits the quality of gradient conditions for the separation of the analytes. Simplex method is used to calculate new gradient profiles in order to reach optimum separations for the selected set of analytes. The Simplex algorithm works stepwise, for each new combination of parameters that describe the gradient profile a new calculation is performed and from the calculated chromatogram the optimization criterion is determined. The proposed method is efficient and may reduce the time and cost of analyses of complex samples with ion-exchange chromatography.


Counterpropagating topological and quantum Hall edge channels.
The survival of the quantum spin Hall edge channels in presence of an external magnetic field has been a subject of experimental and theoretical research. The inversion of Landau levels that accommodates the quantum spin Hall effect is destroyed at a critical magnetic field, and a trivial insulating gap appears in the spectrum for stronger fields. In this work, we report the absence of this transport gap in disordered two dimensional topological insulators in perpendicular magnetic fields of up to 16 T. Instead, we observe that a topological edge channel (from band inversion) coexists with a counterpropagating quantum Hall edge channel for magnetic fields at which the transition to the insulating regime is expected. For larger fields, we observe only the quantum Hall edge channel with transverse resistance close to h/e2. By tuning the disorder using different fabrication processes, we find evidence that this unexpected ν = 1 plateau originates from extended quantum Hall edge channels along a continuous network of charge puddles at the edges of the device.


Priority control factors for heavy metal groundwater contamination in peninsula regions based on source-oriented health risk assessment.
Peninsula regions in China face serious environmental issues, such as heavy metal (HM) groundwater contamination. However, attempts to investigate the pollution sources and health risks of HM contamination in such regions require considerable resources and costs. Moreover, the priority control factors for groundwater HMs remain unclear. In this study, absolute principal component score/multiple linear regression (APCS/MLR) was used to quantify the groundwater pollution sources of typical peninsular areas in China, and a health risk assessment (HRA) was performed to assess the health risks caused by different sources. The results showed that the concentrations of Mn and Fe were higher than those of other HMs, and HM pollution was high in shallow groundwater. The dominant source of HMs in groundwater was agricultural activities (31.12 %), followed by natural sources (26.33 %), industrial activities (22.47 %), and atmospheric deposition (20.09 %). The non-carcinogenic risks to residents were acceptable, whereas the carcinogenic risks were high. Agricultural sources, atmospheric deposition sources, and Cr and As were identified as the priority control factors for HM groundwater contamination. This study has implications for improving the control of groundwater HM contamination in peninsula regions and ensuring sustainable groundwater development.


[Regulation of the immunoglobulin content of the mucous membranes of the uterus: effect of estradiol on immunoglobulin A content].
A was used for the animal experimental investigations standard castration mouse model. Vaginal smears indicated no cyclic changes 14 days after the removal of the ovaries. 12.5 micrograms estradiol benzoate have been injected intramuscularly in this time. 3 days later uterus lavage fluids and tissue homogenates were used for the IgA-test, single radial immunodiffusion. The standard was prepared from mouse colostrum because S-IgA is the dominant IgA in secretions. The results were expressed as U/l selected arbitrary. Our findings of significant increased IgA concentrations in uterus lavage fluid after estradiol stimulation and, in contrary, no changed IgA concentrations in homogenates support the hypothesis, that the secretory component synthesis in the epithelial cells of the uterus is controlled by estrogens.


Trans-Atlantic exchanges have shaped the population structure of the Lyme disease agent Borrelia burgdorferi sensu stricto.
The origin and population structure of Borrelia burgdorferi sensu stricto (s.s.), the agent of Lyme disease, remain obscure. This tick-transmitted bacterial species occurs in both North America and Europe. We sequenced 17 European isolates (representing the most frequently found sequence types in Europe) and compared these with 17 North American strains. We show that trans-Atlantic exchanges have occurred in the evolutionary history of this species and that a European origin of B. burgdorferi s.s. is marginally more likely than a USA origin. The data further suggest that some European human patients may have acquired their infection in North America. We found three distinct genetically differentiated groups: i) the outgroup species Borrelia bissettii, ii) two divergent strains from Europe, and iii) a group composed of strains from both the USA and Europe. Phylogenetic analysis indicated that different genotypes were likely to have been introduced several times into the same area. Our results demonstrate that irrespective of whether B. burgdorferi s.s. originated in Europe or the USA, later trans-Atlantic exchange(s) have occurred and have shaped the population structure of this genospecies. This study clearly shows the utility of next generation sequencing to obtain a better understanding of the phylogeography of this bacterial species.


Is insufficient sleep duration a risk indicator for periodontal disease? A systematic review.
In this study, we conducted a systematic review and meta-analysis to assess whether people who achieved <7 h of sleep were more likely to develop periodontal disease (PD). We executed electronic searches in the PubMed, EMBASE and Cochrane Library, as well as a manual search of articles published by leading journals in related fields, for observational studies, published in English from 1 January 1966 to 31 March 2021.which evaluated the relationship between sleep duration and PD. The Agency for Healthcare Research and Quality (AHRQ) quality evaluation scale was used for the cross-sectional studies, and the random effects model was used to summarize the effect sizes in the included studies with a 95% confidence interval (CI). A total of six cross-sectional studies met the inclusion criteria, totaling 107,777 participants, of which 69,773 had PD. The results of the present indicated that shorter sleep duration (<7 h) is significantly associated with PD (Odd ratio [OR], 1.19; 95% CI, 1.16-1.23; p < 0.001; I2 , 0.0%, I2 interval, 0%-75%). The strength of the sensitivity analysis and cumulative meta-analysis confirmed the reliability of the results. Although the inclusion of only six studies makes it difficult to explore whether there is a publication bias, we found that insufficient sleep duration was closely related to PD, and we therefore speculated that getting enough sleep may help prevent PD.


Evaluation of a Cranial Ultrasound Screening Protocol for Very Preterm Infants.
Cranial ultrasound (cUS) screening is recommended for preterm neonates born before 32 weeks' gestational age (GA). The primary aim of this study was to determine if both a day 3 and day 8 cUS screening examination is necessary for all neonates. A retrospective observational study was performed at a tertiary-level Australian hospital. Frequencies of cranial ultrasound abnormality (CUA) were compared between routine screening performed at postnatal days 3, 8, and 42. Univariate and multivariate analyses of risk factors for intraventricular hemorrhage (IVH) was performed using logistic regression. cUS examinations on 712 neonates born before 32 weeks' GA were included. Neonates were divided into 2 groups: 99 neonates in the 23-25 weeks 6 days GA (group A) and 613 neonates in the 26-31 weeks 6 days GA (group B). All CUA occurred more frequently in group A neonates and in the subset of group B neonates who had defined risk factors. Low-risk group B neonates had lower incidence of CUAs demonstrated on day 8 cUS than high-risk group B neonates, with no significant differences between day 3 and day 8. Logistic regression analysis identified a number of risk factors (vaginal delivery, small for GA, Apgar score <7 at 5 minutes, intubation, patent ductus arteriosus and infection) that were associated with increased frequency of IVH on day 8. In neonates born between 30 and 31 weeks 6 days GA, 35% had a CUA identified. Low-risk preterm neonates born between 26 and 31 weeks 6 days GA, without complications, could be screened with a single early cUS examination around day 8 without missing substantial abnormality.


Grindr Users Take More Risks, but Are More Open to Human Immunodeficiency Virus (HIV) Pre-exposure Prophylaxis: Could This Dating App Provide a Platform for HIV Prevention Outreach?
Technology has changed the way that men who have sex with men (MSM) seek sex. More than 60% of MSM in the United States use the internet and/or smartphone-based geospatial networking apps to find sex partners. We correlated use of the most popular app (Grindr) with sexual risk and prevention behavior among MSM. A nested cohort study was conducted between September 2018 and June 2019 among MSM receiving community-based human immunodeficiency virus (HIV) and sexually transmitted infection (STI) screening in central San Diego. During the testing encounter, participants were surveyed for demographics, substance use, risk behavior (previous 3 months), HIV pre-exposure prophylaxis (PrEP) use, and Grindr usage. Participants who tested negative for HIV and who were not on PrEP were offered immediate PrEP. The study included 1256 MSM, 1090 of whom (86.8%) were not taking PrEP. Overall, 580 of 1256 (46%) participants indicated that they used Grindr in the previous 7 days. Grindr users reported significantly higher risk behavior (greater number of male partners and condomless sex) and were more likely to test positive for chlamydia or gonorrhea (8.6% vs 4.7% of nonusers; P = .005). Grindr users were also more likely to be on PrEP (18.7% vs 8.7% of nonusers; P < .001) and had fewer newly diagnosed HIV infections (9 vs 26 among nonusers; P = .014). Grindr users were also nearly twice as likely as nonusers to initiate PrEP (24.6% vs 14%; P < .001). Given the higher risk behavior and greater acceptance of PrEP among MSM who used Grindr, Grindr may provide a useful platform to promote HIV and STI testing and increase PrEP uptake.


Adolescent Sex and Psyche in Brazil: Surveillance, Critique and Global Mental Health.
Drawing on a historical ethnography conducted in Southern Brazil, this article explores how public health programs for adolescent reproductive and mental health have emerged in Brazil and begun to intersect with the growing field of "global mental health" (GMH). The story I recount begins not in the 2010s with the rapid rise of expert interest in adolescent health within GMH, but in the 1990s, the decade when young teens in Brazil were first coming into contact with practices and approaches in research, schools and clinics that have both underpinned and critiqued the production of an adolescent mental and reproductive health sub-field. In parsing what young women's encounters with the then newly-emerging questionnaires, measurement tools, school-based programs and clinical practices came to mean to them, I use a genealogical approach to consider how histories of education reform, population control, psychoanalysis, social medicine, the transition to democracy, feminism and grass-roots politics all entered the fold, shaping the way adolescent sex-and-psyche materialized as a contested object of expertise. I end by exploring what this case can teach global mental health advocates and social theorists about practices of critique.


Sox13 and M2-like leukemia-associated macrophages contribute to endogenous IL-34 caused accelerated progression of acute myeloid leukemia.
Interleukin 34 (IL-34) mainly plays physiologic and pathologic roles through the sophisticated multi-ligand signaling system, macrophage colony-stimulating factor (M-CSF, CSF-1)/IL-34-CSF-1R axis, which exhibits functional redundancy, tissue-restriction and diversity. This axis is vital for the survival, differentiation and function of monocytic lineage cells and plays pathologic roles in a broad range of diseases. However, the role of IL-34 in leukemia has not been established. Here MLL-AF9 induced mouse acute myeloid leukemia (AML) model overexpressing IL-34 (MA9-IL-34) was used to explore its role in AML. MA9-IL-34 mice exhibited accelerated disease progression and short survival time with significant subcutaneous infiltration of AML cells. MA9-IL-34 cells showed increased proliferation. In vitro colony forming assays and limiting dilution transplantation experiments demonstrated that MA9-IL-34 cells had elevated leukemia stem cell (LSC) levels. Gene expression microarray analysis revealed a panel of differential expressed genes including Sex-determining region Y (SRY)-box 13 (Sox13). Furthermore, a positive correlation between the expressions of IL-34 and Sox13 was detected human datasets. Knockdown of Sox13 rescued the enhanced proliferation, high LSC level and subcutaneous infiltration in MA9-IL-34 cells. Moreover, more leukemia-associated macrophages (LAMs) were detected in MA9-IL-34 microenvironment. Additionally, those LAMs showed M2-like phenotype since they expressed high level of M2-associated genes and had attenuated phagocytic potential, suggesting that LAMs should also contribute to IL-34 caused adverse phenotypes. Therefore, our findings uncover the intrinsic and microenvironmental mechanisms of IL-34 in AML and broadens the knowledge of M-CSF/IL-34-CSF-1R axis in malignancies.


The effect of liposuction on inferior epigastric perforator vessels: a prospective study with color Doppler sonography.
The authors investigated the effect of abdominal liposuction performed by superficial subdermal liposuction technique on inferior epigastric perforators. We aimed to determine whether previous liposuction is a contraindication to the use of an abdominal flap. The perforators in the abdominal region in 6 patients were marked preoperatively by color and pulsed-wave Doppler sonography (CDS), which gave a morphologic and flowmetric representation. The parameters studied with CDS were the location of the perforators, the diameters of the arteries and veins, and the flow velocity. These parameters were evaluated by the same method preoperatively and 6 months postoperatively. The Student t test was employed to assess differences between pre- and postoperative values of variables. The results of our study led us to conclude that prior abdominal liposuction does no significant injury to most perforating vessels. However, CDS aimed to study the existence and the quality of perforators should be done before planning an abdominal flap.


1,5-Bis[1-(4-bromo-phen-yl)ethyl-idene]thio-carbonohydrazide.
The asymmetric unit of the title compound, C17H16Br2N4S, contains two independent mol-ecules in which the benzene rings form dihedral angles of 20.0 (1) and 55.3 (1)°. In the crystal, a pair of N-H⋯S hydrogen bonds link the two different independent mol-ecules into a dimer.


SARS-CoV-2 Next Generation Sequencing (NGS) data from clinical isolates from the East Texas Region of the United States.
The SARS-CoV-2 virus has evolved throughout the pandemic and is likely to continue evolving into new variants. Some of these variants may affect functional properties, including infectivity, interactions with host immunity, and disease severity. And compromised vaccine efficacy is an emerging concern with every new viral variant. Next-generation sequencing (NGS) has emerged as the tool of choice for discovering new variants and understanding the transmission dynamics of SARS-CoV-2. Deciphering the SARS-CoV-2 genome has enabled epidemiological survivance and forecast of altered etiologically. Clinical presentations of the infection are influenced by comorbidities such as age, immune status, diabetes, and the infecting variant. Thus, clinical management and vaccine efficacy may differ for new variants. For example, some monoclonal antibody treatments are variant-specific, and some vaccines are less efficacious against the omicron and delta variants of SARS-CoV-2. Consequently, determining the local outbreaks and monitoring SARS-CoV-2 Variants of Concern (VOC) is one of the primary strategies for the pandemic's containment. Although next-generation sequencing (NGS) is a gold standard for genomic surveillance and variant discovery, the assays are not approved for variant diagnosis for clinical decision-making. Advanta Genetics, Texas, USA, optimized Illumina COVID-seq protocol to reduce cost without compromising accuracy and validated the Illumina COVID-Seq assay as a Laboratory Developed Test (LDT) according to the guidelines prescribed by the College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). The whole genome of the virus was sequenced in (n = 161) samples from the East Texas region using the Illumina MiniSeq® instrument and analyzed by using Illumina baseSpace (https://basespace.illumina.com) bioinformatics pipeline. Briefly, the library was prepared by using Illumina COVIDSeq research use only (RUO) kit, and the individual libraries were normalized using the DNA concentration measured by Qubit Flex Fluorometer, and the pooled libraries were sequenced on Illumina MiniSeq® Instrument. Illumina baseSpace application was used for sequencing QC, FASTQ generation, genome assembly, and identification of SARS-CoV-2 variants. This whole genome shotgun project (n = 161) has been deposited at GISAID.


Polymyxin causes cell envelope remodelling and stress responses in mcr-1-harbouring Escherichia coli.
Polymyxins remain important last-line antibiotics against multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance is emerging and the mobile polymyxin resistance gene, mcr, is contributing to the wide dissemination of polymyxin resistance, especially among Escherichia coli, with mcr-1 being the most commonly found variant. The objective of this study was to provide mechanistic insights into concentration-dependent transcriptomic responses of mcr-harbouring E. coli following polymyxin treatment. An mcr-1-carrying clinical isolate of E. coli (LH30) was treated with polymyxin B at 2 and 8 mg/L. Bacterial cultures were collected before and 1 h following treatment for viable counting and transcriptomic analysis. Growth of E. coli LH30 was unaffected by 2 mg/L polymyxin B, whereas killing of approximately 2 log10 colony-forming units/mL occurred with 8 mg/L at 1 h. All four phosphoethanolamine (pEtN) transferase genes (mcr-1, eptA, eptB and eptC) were upregulated (fold change 2.4-4.0) by 8 mg/L polymyxin B, indicating that pEtN modifications were the preferred polymyxin resistance mechanism. The higher polymyxin B concentration also affected the expression of genes involved in fatty acid, lipopolysaccharide, lipid A, phospholipid biosynthesis, iron homeostasis and oxidative stress pathways. This transcriptomic analysis revealed that cell envelope remodelling, pEtN modification, iron acquisition and oxidative stress protective mechanisms play a key role in the survival of mcr-carrying E. coli treated with polymyxin. These findings provide new mechanistic information at the gene expression level to counter polymyxin resistance.


Characterizing optimum electrospinning conditions for graft urethanized Poly(Vinyl Alcohol)(U-PVA).
Poly(vinyl alcohol) (PVA) is a water-soluble polymer that has been widely used in medical and pharmaceutical applications. For this study, we grafted urea to PVA to enhance its wettability and solubility in water. We used a scanning electron microscope (SEM) to characterize the electrospun graft urethanized poly(vinyl alcohol) U-PVA and determine the best electrospinning conditions. The capillary-collector distance, applied voltage, and flow rate all had notable effects on fiber diameter and morphology. When we increased the capillary-collector distance to 20 cm and set the applied voltage to 25 kV, the fiber diameter and bead formation decreased, while decreasing the flow rate to 1 mL/h resulted in a homogeneous fibrous structure with an average fiber diameter equal to 159 ± 59.3 nm. We compared the wettabilities, Fourier transform infra-red FTIR spectra and insulin drug release of graft U-PVA and pure PVA electrospun specimens. Grafting urea to PVA enhanced its wettability, and drug release rate with time; indicating the effectiveness of graft U-PVA as a drug delivery system with high drug-release rates.


Studies on the biosynthesis of sulfolipids in the Diatom Nitzschia alba.
Labeling of sulfolipids in Nitzschia alba was studied after growth of the cells in media containing L-[35S]cystine, L-[35S], L-[35S]cysteine, L-[35S]-methionine or a mixture of L-[Me-3H]methionine and L-[35S]methionine, [35S]Cysteine or [35S]cystine labeled the deoxyceramide sulfonate and the sulfonium analog, phosphatidylsulfocholine (and its lyso derivative) but not the sterol sulfate nor the sulfoquinovosyl diglyceride; [35S]methionine labeled only the phosphatidylsulfocholine and its lyso derivative. With the [35S]- and [Me-3H]methionine mixture (3H/35S ratio 1.0) the phosphatidylsulfocholine had a 3H/35 S ratio of 1.5 indicating that both sulfonium methyl groups were derived from methionine. Probable biosynthetic pathways for these novel sulfolipids are discussed.


Cerebral arterial air emboli on immediate post-endovascular treatment CT are associated with poor short- and long-term clinical outcomes in acute ischaemic stroke patients.
To determine the incidence and predictors of cerebral arterial air emboli (CAAE) on immediate post-endovascular treatment (EVT) dual-energy CT (DECT) in acute ischaemic stroke (AIS) patients, and describe their association with clinical outcomes. EVT records from 2010 to 2019 were screened. Exclusion criteria included intracerebral haemorrhage on post-EVT DECT. In the affected middle cerebral artery (MCA)-territory, circular and linear (length ≥ 1.5*width) CAAE were counted. Clinical data were collected from prospective records. The modified Rankin Scale (mRS) at 90 days was the primary outcome. Multivariable linear, logistic, and ordinal regression were used to analyse the effect of (1) linear CAAE and (2) isolated circular CAAE. Out of 651 EVT-records, 402 patients were included. In 65 patients (16%), at least one linear CAAE was found in the affected MCA-territory. 17 patients (4%) showed isolated circular CAAE. Multivariable regression showed an association between both the presence and the number of linear CAAE and the mRS at 90 days (presence: adjusted (a)cOR 3.10, 95%CI 1.75-5.50; number: acOR 1.28, 95%CI 1.13-1.44), NIHSS at 24-48 h (presence: aβ 4.15, 95%CI 1.87-6.43; number: aβ 0.88, 95%CI 0.42-1.34), mortality at 90 days (presence: aOR 3.34, 95%CI 1.51-7.40; number: aOR 1.24, 95%CI 1.08-1.43) and stroke progression (presence: aOR 4.01, 95%CI 1.96-8.18; number: aOR 1.31, 95%CI 1.15-1.50). Isolated circular CAAE were not significantly associated with any outcome measure. CAAE were found frequently on post-EVT CT imaging. The presence and the number of linear CAAE, but not circular CAAE, are associated with unfavourable short- and long-term clinical outcomes.


Inherited 3-methylglutaconic aciduria in two brothers--another defect of leucine metabolism.
Two brothers, aged 7 and 5 years, who excreted large amounts of the leucine metabolites 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid, are described. The excretion of these metabolites could be enhanced by increasing the leucine intake. Restriction of the protein intake resulted in a marked reduction of the metabolite excretion. However, the excretion of the ultimate leucine metabolite, 3-hydroxy-3-methylglutaric acid, remained unchanged at a low level. The only clinical abnormality was speech retardation. A (partial) deficiency of 3-methylglutaconyl coenzyme A hydratase is proposed to be the most likely underlying defect.


Upregulation of potential regulatory signaling molecules correlate with androgen receptor splice variants AR-V7 and AR-V567es in prostate cancer metastasis.
Androgen receptor splice variants (AR-Vs) produced by alternative splicing of the AR play an important role in the treatment resistance and progression of prostate cancer (PCa). In this study, two most common AR variants and how they associate with the inflammatory response (NF-Kβ) and regulatory transcriptional activity (HSP-27) genes were investigated in patients with PCa and metastatic PCa (Met-PCa). Our study was carried out with the whole blood obtained from 25 healthy control subjects, 25 PCa patients and 39 Met-PCa patients. We examined the expression levels of AR, AR-V7 and AR-V567es genes via Real-time PCR and those of HSP-27 and NF-Kβ via ELISA method. AR, AR-V7 and AR-V567es expressions were observed in 84.61%, 64.1%, 23.07% of Met-PCa patients respectively. The expression levels of full-length AR and variants (AR-V7 and AR-V567es) were associated with the prostate cancer stage. In the Met-PCa, the expression levels of AR, AR-V7 and AR-V567es were associated with the Gleason Scores but not with the PSA levels. AR-V7 expression levels in stage T4 patients significantly increased. NF-Kβ and HSP-27 protein levels were significantly higher in Met-PCa patients. Our findings highlight the targeting of the proteostasis and inflammation pathways through inhibiting HSP-27 and NF-Kβ. This might be a valuable strategy to overcome anti-androgen resistance and improve drug therapy in Met-PCa patients whose gene expression levels of AR-V7 and AR-V567es variants are high.


Exogenous myristic acid acylates proteins in cultured rat hepatocytes.
Fatty acid acylation is a functionally important modification of proteins. In the liver, however, acylated proteins remain largely unknown. This work was aimed at investigating fatty acid acylation of proteins in cultured rat hepatocytes. Incubation of these cells with [9,10-3H] myristic acid followed by two-dimensional electrophoresis separation of the delipidated cellular proteins and autoradiography evidenced the reproducible and selective incorporation of radioactivity from the precursor into 18 well-resolved proteins in the 10--120 kDa range and the 4--7 pH range. Radiolabeling of these proteins resulted from covalent linkage to the precursor [9,10-3H] myristic acid or to its elongation product, palmitic acid. The majority of the covalent linkages between the proteins and the fatty acids were broken by base hydrolysis, which indicated that the linkage was of thioester or ester-type. Only one of the studied proteins was attached to myristic acid via an amide linkage which resisted the basic treatment but was broken by acid hydrolysis. After incubation with [9,10-3H] palmitic acid, only two proteins previously detected with myristic acid were radiolabeled. Finally, the identified acylated proteins may be grouped into two classes: proteins involved in signal transduction (the alpha subunit of a heterotrimeric G protein and several small G proteins) and cytoskeletal proteins (cytokeratins, actin).


Simultaneous quantification of total medium- and long-chain fatty acids in human milk by capillary gas chromatography with split injection.
Four different quantification methods for the capillary gas chromatographic determination of medium-chain fatty acids (6:0-12:0) and myristic acid in human milk samples, using a split injector, were compared. Odd-carbon-numbered fatty acids (5:0-17:0) were added as internal standards. Each medium-chain fatty acid and myristic acid was calculated on the basis of: the peak area of the internal standard with one methylene group less; the peak area of the internal standard with one methylene group more; half the sum of the peak areas of the internal standards with one methylene group less and more (bracketting method); the peak area of 17:0. The peak-area ratio of each analyte and 17:0 in a standard was found to be subject to an unacceptably high coefficient of variation. From the methods using internal standards with one methylene group more and less, the bracketting method was found to be the best, resulting in recoveries close to 100%, with the lowest coefficients of variation. The method was applied for the determination of the fatty acid composition of mature milk samples of 47 Curaçaoan women.


Pediatric cervical intraosseous schwannoma.
Intraosseous schwannoma of the spine is an extremely rare tumor, with only 18 cases reported so far in the literature. We describe the 1st case of intraosseous schwannoma in the pediatric age group, which was treated successfully, and we review the pertinent literature.


A Revised Framework to Evaluate the Consistency Assumption Globally in a Network of Interventions.
The unrelated mean effects (UME) model has been proposed for evaluating the consistency assumption globally in the network of interventions. However, the UME model does not accommodate multiarm trials properly and omits comparisons between nonbaseline interventions in the multiarm trials not investigated in 2-arm trials. We proposed a refinement of the UME model that tackles the limitations mentioned above. We also accompanied the scatterplots on the posterior mean deviance contributions of the trial arms under the network meta-analysis (NMA) and UME models with Bland-Altman plots to detect outlying trials contributing to poor model fit. We applied the refined and original UME models to 2 networks with multiarm trials. The original UME model omitted more than 20% of the observed comparisons in both networks. The thorough inspection of the individual data points' deviance contribution using complementary plots in conjunction with the measures of model fit and the estimated between-trial variance indicated that the refined and original UME models revealed possible inconsistency in both examples. The refined UME model allows proper accommodation of the multiarm trials and visualization of all observed evidence in complex networks of interventions. Furthermore, considering several complementary plots to investigate deviance helps draw informed conclusions on the possibility of global inconsistency in the network. We have refined the unrelated mean effects (UME) model to incorporate multiarm trials properly and to estimate all observed comparisons in complex networks of interventions.Forest plots with posterior summaries of all observed comparisons under the network meta-analysis and refined UME model can uncover the consequences of potential inconsistency in the network.Using complementary plots to investigate the individual data points' deviance contribution in conjunction with model fit measures and estimated heterogeneity aid in detecting possible inconsistency.


[Anatomical variations of the clinoid process of the human sphenoid bone].
The authors analysed 270 human adult skulls of both sexes, in order to demonstrate the fusion of clinoid process of sphenoid. It was verified only 38 cases under several shapes. According to our results obtained, may be concluded: a) the fusion between the anterior and medium clinoid processes occurred in 17 cases (6.27%), being that in 11 cases (4.05%) bilaterally; b) between the medium and posterior clinoid processes occurred in six cases (2.22%); c) between the anterior and posterior clinoid processes occurred bilaterally in six cases (2.22%); d) between the three processes occurred in nine cases (3.04%).


Percutaneous fixation of hand fractures using locked K-wires: mechanical analysis and clinical application.
Closed percutaneous wire fixation of hand fractures frequently requires protection with external splintage. This splintage increases the risk of joint stiffness, prolongs recovery time, and increases therapy input. We have developed a method of linking external Kirschner wires (K-wires), using a metal clamp, after their insertion, so as to increase the security of fixation and facilitate postoperative mobilization. The mechanical properties of this method have been assessed in vitro and compared with conventionally fixed, unlinked, K-wires. We have been able to establish that the linked K-wire system is better able to resist loosening. This work proposes that linkage of K-wires permits omission of all additional external splintage, with no detriment to management. The technique has been applied in clinical cases over the past 8 years and results of treatments were evaluated mainly to detect unexpected complications. We report a low rate of complications and good results in terms of bone healing and recovery of function.


Antigenic competition in the immune response against protein mixtures: strain-specific non-immunogenicity of Escherichia coli antigens.
Antigenic competition is argued to impair the immune response on the level of accessory cell-dependent antigen presentation to responsive T-cells (regulated by MHC encoded Ir gene products). A possible influence of these mechanisms on in vivo immunization with antigen mixtures was investigated by using cytoplasmic extracts of four different strains of Escherichia coli as antigen sources for immunizing rabbits. The immune response against these antigen mixtures was tested by crossed immune electrophoresis (CIE) and immunoblotting (IB) in a homologous system (a given antigen extract of one strain against the corresponding antisera) and in the heterologous system (antigen extract of one strain against the antisera of different other strains). Several proteins were non-immunogenic in the extract of one strain but elicited good antibody responses in other strains. One of the strain-specific non-immunogenic proteins was purified and revealed a normal immune response upon immunization. The data suggest that different antigenic competition effects are induced by different protein compositions of antigen mixtures. This strain-specific competition seems to determine the immunogenicity of certain molecules (and not only the immunogenic properties of the molecules themselves). Furthermore this method offers a practical approach to increase the antibody production against weak immunogens in antigen mixtures.


Long-chain polyunsaturated fatty acid status in children, adolescents and adults with phenylketonuria.
Patients with phenylketonuria have been reported to be deficient in long-chain polyunsaturated fatty acids (LCPUFAs). It has been postulated that good compliance with the dietary regimen negatively influences LCPUFA status. In 36 patients with phenylketonuria and 18 age-matched healthy control subjects LCPUFA-levels in plasma phospholipids and cholesteryl esters, erythrocyte phosphatidylcholine and phosphatidylethanolamine were evaluated. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels did not differ significantly between patients and control subjects in plasma and erythrocyte fractions. There was a significant negative correlation between SDS (standard deviation) scores of DHA-levels in erythrocyte parameters from the respective age-matched control group and patients' concurrent and long-term phenylalanine levels for erythrocyte phosphatidylethanolamine and erythrocyte phosphatidylcholine. Patients with lower (higher) phenylalanine levels had positive (negative) DHA-SDS. In contrast to previous reports we did not find lower LCPUFA-levels in patients with phenylketonuria compared to age-matched healthy control subjects. Good dietary control was associated with better LCPUFA status.


The presequence of yeast 5-aminolevulinate synthase is not required for targeting to mitochondria.
A truncated form of the yeast mitochondrial 5-aminolevulinate (ALA) synthase was constructed by deletion of the first 75 amino acid residues of its precursor form. This truncated ALA synthase which lost its entire presequence and 40 residues of the mature part possesses a new amino terminus quite different from a typical mitochondrial presequence. This modified protein expressed in vivo is found entirely located within mitochondria. Although it was now unable to reach the matrix space, it was internalized as shown by its resistance to protease in isolated mitochondria. Pulse-chase radiolabeling in the presence of an uncoupler suggests that a membrane potential is not required for the targeting of this truncated ALA synthase. Thus, the amino-terminal signal, if indispensable as a matrix targeting signal, could be replaced by an internal sequence or a particular folding for recognition by the import machinery.


Localization of antigen defined by a monoclonal antibody to human 32-kDa insulin-like growth factor-binding protein in the sheep uterus at preimplantation stages of pregnancy.
Employing a murine monoclonal antibody to pregnancy-associated endometrial alpha I-globulin, a 32-kDa insulin-like, growth factor-binding protein (IGF-BP) and major product of the decidualized endometrium in the human, reactivity has been detected in the luminal epithelium of the sheep endometrium during the preimplantation period of pregnancy. Staining was associated with supranuclear regions of the cytoplasm. Reactivity was restricted to the pregnant uterus and was distributed throughout the luminal epithelium in both caruncular and intercaruncular regions. The reactivity was absent from endometrial glands in intercaruncular regions. Staining was first detected at day 10, peaked at day 14 of gestation and was absent by day 16. The implications of the induction of the production of this protein by the preimplantation blastocyst in the luminal epithelium is discussed with reference to the potential role of IGF-BP in IGF action in the embryo.


Convergence of basolateral amygdaloid and mediodorsal thalamic projections in different areas of the frontal cortex in the rat.
The extent of convergence of mediodorsal thalamic and amygdalar afferents on the rat's frontal cortex was studied by tracing retrogradely labeled cells following injections of horseradish peroxidase (HRP). HRP was applied iontophoretically in extremely small injections throughout all areas of the frontal cortex. The following organization was revealed: Converging inputs from the mediodorsal nucleus and the amygdala are observed in the posterior parts of the pre- and infralimbic areas, in the posterior half of the dorsal and ventral agranular insular areas and in the lateral and dorsal precentral areas. Both mediodorsal and amygdaloid afferents reach the dorsal tip of the frontal cortex. Only the mediodorsal afferents were found to terminate in the anterior parts of the pre- and infralimbic areas and in the anterior part of the dorsal division of the anterior cingulate area and in the medial precentral area. On the lateral side of the hemisphere the anterior halves of the dorsal and ventral agranular insular areas receive mediodorsal afferents. Amygdaloid, but not mediodorsal afferents, were found following injections into the more posterior parts of the lateral precentral area. These results are discussed with respect to the extent of the prefrontal cortex in the rat and its definability as a target area of subcortical nuclei. Functional aspects of the anatomical convergence of connections within the so-called basolateral limbic circuit are outlined.


Interannual variability and trends of combustion aerosol and dust in major continental outflows revealed by MODIS retrievals and CAM5 simulations during 2003-2017.
Emissions and long-range transport of mineral dust and combustion-related aerosol from burning fossil fuels and biomass vary from year to year, driven by the evolution of the economy and changes in meteorological conditions and environmental regulations. This study offers both satellite and model perspectives on the interannual variability and possible trends of combustion aerosol and dust in major continental outflow regions over the past 15 years (2003-2017). The decade-long record of aerosol optical depth (AOD, denoted as τ), separately for combustion aerosol (τ c) and dust (τ d), over global oceans is derived from the Collection 6 aerosol products of the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard both Terra and Aqua. These MODIS Aqua datasets, complemented by aerosol source-tagged simulations using the Community Atmospheric Model version 5 (CAM5), are then analyzed to understand the interannual variability and potential trends of τ c and τ d in the major continental outflows. Both MODIS and CAM5 consistently yield a similar decreasing trend of -0.017 to -0.020 per decade for τ c over the North Atlantic Ocean and the Mediterranean Sea that is attributable to reduced emissions from North America and Europe, respectively. On the contrary, both MODIS and CAM5 display an increasing trend of +0.017 to +0.036 per decade for τ c over the tropical Indian Ocean, the Bay of Bengal, and the Arabian Sea, which reflects the influence of increased anthropogenic emissions from South Asia and the Middle East in the last 2 decades. Over the northwestern Pacific Ocean, which is often affected by East Asian emissions of pollution and dust, the MODIS retrievals show a decreasing trend of -0.021 per decade for τ c and -0.012 per decade for τ d, which is, however, not reproduced by the CAM5 model. In other outflow regions strongly influenced by biomass burning smoke or dust, both MODIS retrievals and CAM5 simulations show no statistically significant trends; the MODIS-observed interannual variability is usually larger than that of the CAM5 simulation.


Mating affects reproductive investment into eggs, but not the timing of oogenesis in the flesh fly Sarcophaga crassipalpis.
We examined the effects of mating on reproductive investment and the timing of oogenesis in the flesh fly Sarcophaga crassipalpis by exposing females to males or not. All females exposed to males were mated within a few days and we found that mating affected reproductive investment. Virgin females not exposed to males produced a large clutch of eggs ( approximately 91), but females exposed to males and mated produced 10% more. There was no effect of mating on egg length or mass. There was also no effect of mating on the timing of oogenesis. Females in both treatments provisioned their eggs at the same rate with yolk first becoming visible in the oocytes on day three of adulthood and complete provisioning of eggs occurring by the seventh day of adulthood. We examined the biochemical basis of egg provisioning by identifying the yolk proteins and quantifying their blood titer during the oogenic period in both, females exposed to males and mated and those not exposed to males. There was no difference in the timing of the first appearance, peak titer, or disappearance of yolk proteins in the blood between the two treatments. However, consistent with our observation of greater egg production in mated females, these females contained a greater peak yolk protein titer.


Hope from the perspective of people with schizophrenia (Korea).
Studies about hope, a major contributing factor to recovery, are relatively rare in mental health literature. This qualitative study was conducted to explore the nature of hope in 25 Koreans with schizophrenia (16 men and 9 women). Participants were asked to respond to three questions about hope: What does hope mean to you? What do you hope for? Where does hope come from for you? Hope in people with schizophrenia is similar to hope in people without schizophrenia; hope comes from loving and being loved in interpersonal relationships.