Reduction of peritoneal adhesion formation by colchicine: a comparative study in the rat.
Colchicine inhibits processes known to be involved in the pathogenesis of peritoneal adhesions. Daily administration of 50 micrograms of colchicine to 22 rats significantly diminished adhesion formation, as compared with dexamethasone-treated and untreated rats. Rats that developed at least three adhesions of grade 3 (scale 0 to 4) were strikingly less prevalent among the colchicine-treated animals than the untreated group (9.1% versus 40.9%, P less than 0.001). The double product of the number and grading of adhesions was significantly lower (P less than 0.05) in the colchicine group. Colchicine is more effective than dexamethasone in inhibiting adhesion formation in the rat.


The symptom experience in the first 100 days following allogeneic hematopoietic stem cell transplantation (HSCT).
Despite advances in allogeneic hematopoietic stem cell transplantation (HSCT), post-transplant complications are common, and patients' symptom experience has not been well documented. To characterize the symptom experience of adult patients pre-transplantation and days 0, 30, and 100 after allogeneic HSCT. Data from 76 participants enrolled in a prospective health-related quality of life (HRQL) study were used. Symptom occurrence, distress, and clusters were determined based on the 11 symptoms of the Symptom Distress Scale (SDS). Participants were on average 40 years old (SD +/- 13.5). The majority (54%) received reduced intensity conditioning. Prevalent symptoms included fatigue (68%) and worry (68%) at baseline, appetite change (88%) at day 0, and fatigue at days 30 (90%) and 100 (81%). Participants reported the following symptoms as severely distressing: worry (16%) [baseline], insomnia (32%) [day 0], appetite change (22%) [day 30], and fatigue (11%) [day 100]. The total SDS score was highest at day 0 (M = 26.6 +/- 7.6) when the highest number of symptoms were reported [median = 8 (1-11)]. Symptoms formed clusters comprised of fatigue, appearance change, and worry at baseline, and fatigue, insomnia, and bowel changes at days 0 and 30. Compared to those with low symptom distress, participants with moderate/severe symptom distress reported poorer HRQL. Allogeneic HSCT patients present for transplantation with low symptom distress yet experience multiple symptoms and high symptom distress after HSCT conditioning. Understanding the symptom experience of allogeneic HSCT patients can guide management strategies and improve HRQL.


Blood pressure control in end-stage renal disease in man: indirect evidence of a complex pathogenic mechanism besides renin or blood volume.
1. In twenty-three uraemic patients on regular dialysis, plasma renin activity and blood volume were measured before and after a single dialysis. Three groups were identified; the first had a low or normal plasma renin activity and a high or normal blood volume, the second had a high plasma renin activity and a low blood volume and the third had both variables above normal. 2. In spite of these differences, diastolic blood pressure before and after dialysis was the same in the three groups and multiple regression analyses failed to demonstrate any dependence of blood pressure on plasma renin activity, blood volume or body weight taken separately or together. 3. We conclude that other factors besides plasma renin activity and blood volume are important in maintaining arterial hypertension in terminal renal failure.


[Frosted branch angiitis : Clinical findings and Spectralis OCT follow-up].
Frosted branch angiitis is a special form of retinal vasculitis, which has only rarely been reported in the literature. Although the majority of cases of frosted branch angiitis are idiopathic, a systematic clinical work-up should be done in order to exclude other causes, such as infectious and autoimmune diseases. The aim of this study was to correlate the clinical findings with the images obtained during follow-up by spectral domain optical coherence tomography (OCT).


Increased radiation sensitivity of head and neck squamous cell carcinoma with sphingosine kinase 1 inhibition.
Sphingosine kinase 1 (SphK1) is an important regulator of apoptosis, survival, and proliferation in cancer cells. SphK1 expression in head and neck squamous cell cancer (HNSCC) cell lines and tumor tissue was assessed, and the efficacy of SphK1 knockdown in increasing tumor radiosensitivity was evaluated in vitro and in vivo. Expression of SphK1 was determined by immunohistochemistry, Western blot, and real-time polymerase chain reaction (RT-PCR) in 34 prospectively collected HNSCC tumor samples. HNSCC cell lines squamous cell carcinoma (SCC)-15 and SCC-25 were treated with SphK1 inhibitor SKI-II and siRNA targeting SphK1 with and without radiation, and the cell viability was assessed. SCC-15 cells with and without transfection of SphK1 siRNA were then injected into athymic nude mice to develop tumor xenografts, and these 2 groups were further divided into 1 group that received radiation and 1 group that did not. Tumor size was measured over 18 days, when the animals were killed and the tumors were evaluated by immunohistochemistry. SphK1 is found in both HNSCC cell lines and human tumor samples, with higher expression correlated with advanced tumor stage, nodal involvement, and recurrence. In vitro, both SCC-15 and SCC-25 were found to be radioresistant; however, they were sensitized by administration of SKI-II and transfection with siRNA targeting SphK1. In vivo, SphK1-siRNA transfected xenografts were decreased in size compared with both nonradiated control and radiated control mice, whereas mice with both SphK1-siRNA and radiation treatment showed a synergistic reduction in tumor volume. Histopathologic analysis demonstrated a decreased proliferative state in SphK1-siRNA transfected tumors. SphK1 is upregulated in HNSCC, and inhibition of SphK1 sensitizes HNSCC to radiation-induced cytotoxicity.


The structural modification and biological evaluation of tetrahydrothienopyridine derivatives as selective BChE inhibitors.
A series of tetrahydrothienopyridine derivatives have been designed, synthesized, and evaluated as selective BChE inhibitors. Compounds were analyzed via HRMS, 1H NMR, and 13C NMR. The inhibitory effects were evaluated according to the method of Ellman et al. 6n was the most potent and selective inhibitor against BChE (eeAChE IC50 = 686.4 ± 478.6 μM, eqBChE IC50 = 10.5 ± 5.0 nM, SI = 6.5*104, hBChE IC50 = 32.5 ± 6.5 nM). Cell-based assays have confirmed the low neurotoxicity of 6a and 6n and their moderate neuroprotective effects. Compounds 6a and 6n provide novel chemical entities for the treatment of Alzheimer's disease.


Dietary effects of harmine, a β-carboline alkaloid, on development, energy reserves and α-amylase activity of Plodia interpunctella Hübner (Lepidoptera: Pyralidae).
The physiological and developmental effects of harmine, a β-carboline alkaloid, on the insect pest Plodia interpunctella have been analyzed. When added at the larval diet, harmine induced a strong reduction of larvae weight, cannibalism between larvae, in addition to significant mortality. On the other hand, it caused a remarkable development disruption, manifested by both delay and reduction of pupation and adult emergence. Using spectrophotometric assays, we have shown that harmine ingestion provoked a severe reduction in protein, glycogen and lipid contents. Beside, when larvae fed harmine, the activity of the digestive enzyme α-amylase was strongly reduced. In conclusion, our experiments clearly show the susceptibility of P. interpunctella to harmine ingestion revealing the potent bioinsecticidal effect of harmine.


Tendon ruptures and median nerve damage after Hamas total wrist arthroplasty.
This article describes complications due to an incorrectly positioned Hamas-designed total wrist prosthesis in a 68-year-old woman with rheumatoid arthritis. At operation the median nerve was found to be directly impinged upon by the rim of the distal portion of the prosthesis. There were divisions of the superficialis tendon to all four fingers, the profundus tendon to the index finger, and partial division of the profundus to the long finger. The prosthesis was removed, and the wrist stabilized with a Steinmann pin in the radius and the second metacarpal.


[Status of the electrolyte balance of the gastric juice during stimulation of secretion by histamine].
The content of electrolytes (Na+, K+, Ca2+) in human basal secrete has been determined before and after injection of histamine in gastric juice and insoluble mucus in healthy people. Electrolytes in the mucous membrane of the stomach, gastric juice and insoluble mucus have been determined in dogs with stomach fistula after Basow. Species peculiarities have been marked in electrolyte content change during gastric secretion.


Computed tomography histogram in the pathologic definition of supratentorial brain tumors.
After studying the histograms of 87 supratentorial brain tumors and 4 abscesses before and after contrast medium injection and analyzing the results, we attempt to determine characteristic signs of the various kinds of tumors in order to improve their pathologic definition. The meningiomas, astrocytomas, and abscesses seem to show the most standard signs. The metastases are the most variable kind of tumors.


Effect of iron nanoparticles and conventional sources of Fe on growth, physiology and nutrient accumulation in wheat plants grown on normal and salt-affected soils.
Salt stress is becoming a serious problem for the global environment and agricultural sector. Different sources of iron (Fe) can provide an eco-friendly solution to remediate salt-affected soils. The Fe nanoparticles (FeNPs) and conventional sources of Fe (iron-ethylene diamine tetra acetic acid; Fe-EDTA; and iron sulfate; FeSO4) were used to evaluate their effects on wheat crop grown in normal and salt-affected soils. Application of FeNPs (25 mg/kg) on normal soil increased the dry weights of wheat roots, shoots, and grains by 46%, 59%, and 77%, respectively. In salt-affected soil, FeNPs increased the dry weights of wheat roots, shoots, and grains by 65%, 78%, and 61%, respectively. The application of FeSO4 and Fe-EDTA increased the growth parameters of wheat in both normal and salt-affected soils compared to the respective controls. The photosynthetic parameters, including chlorophyll a (50%), chlorophyll b (67%), carotenoids (62%), and total chlorophyll contents (50%), were increased with the application of FeNPs under salt stress. The FeNPs increased plant-essential nutrients like iron, zinc, calcium, magnesium, and potassium in both normal and salt-affected soils. The experiment revealed that the application of Fe plays a significant role in enhancing the growth of wheat on alkaline normal and salt-affected soils. Maximum growth response was recorded with FeNPs than other Fe sources. The future must be focused on long term field experiments to economize the application of FeNPs on a large scale for commercialization.


Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy.
To determine the rate of progression of white matter lesions and hemorrhages in a cohort with cerebral amyloid angiopathy (CAA). The authors analyzed data from 26 patients with possible (3) or probable (23) CAA, diagnosed by the Boston Criteria. Brain maps of white matter hyperintensities, normalized to head size (nWMH), were created by blinded computer-assisted segmentation of MRI images obtained at baseline and after a median follow-up interval of 1.1 year. There was a substantial nWMH volume increase over the interscan interval (median 0.5 mL/year, interquartile range 0.1 to 2.8, p < 0.001). The median yearly increase, expressed as a percentage of the baseline WMH volume, was 18%. The characteristic most strongly associated with nWMH volume increase was the baseline nWMH volume (r = 0.57, p = 0.002). The volume of nWMH progression was also associated with history of cognitive impairment (median 5.0 mL/year in cognitively impaired subjects vs 0.3 mL/year in cognitively unimpaired, p = 0.02) but not age or hypertension. This association remained present in an analysis stratified by baseline WMH volume. New hemorrhages, including asymptomatic microbleeds, were seen in 46% of subjects. The number of new MRI hemorrhages correlated strongly with baseline nWMH (r = 0.53, p = 0.005) but not with nWMH progression (r = 0.22, p = 0.28). There is a progressive increase in white matter lesions in subjects with cerebral amyloid angiopathy. The association of white matter lesions with incident lobar hemorrhages suggests that white matter damage may reflect a progressive microangiopathy due to cerebral amyloid angiopathy.


Prospective trial of the ultrasonic dissector in thyroid surgery.
Use of the ultrasonic dissector in thyroid surgery is becoming more prevalent, with reduced operative time and incision size reported. We assessed the value of the harmonic scalpel in routine thyroid lobectomy. We conducted a single blind, prospective pilot study of 52 euthyroid patients requiring thyroid lobectomy. Those with lesions not suitable for resection through a 4-cm incision, a history of thyroiditis, or uncontrolled thyroid dysfunction were excluded. Patients were allocated to 1 of 2 groups: group I (n = 31), thyroid lobectomies using conventional surgical techniques; or group II (n = 21), thyroid lobectomies using the ultrasonic dissector. Outcomes for the 2 patient groups were comparable. There was no significant difference in operative time or incision size. The ultrasonic dissector does not confer any quantifiable benefit in routine thyroid lobectomy when compared with conventional techniques. This is the first reported series in which its use has not reduced operative time.


KIF15 contributes to cell proliferation and migration in breast cancer.
A number of kinesin proteins (KIFs) have been implicated in the development of multiple cancers. However, little is known about the expression and function of KIF15 in human breast cancer. Herein, we detected KIF15 expression in breast cancer tissues and paired adjacent normal tissues using immunohistochemistry and quantitative real-time polymerase chain reaction analysis, and the correlation of KIF15 expression with clinicopathological parameters was evaluated statistically. The role of KIF15 in cell proliferation, migration, tumor growth and metastasis of breast cancer cells was investigated in vitro and in vivo, and we explored potential molecular mechanisms underlying the effects of KIF15 in breast cancer through western blot analysis. The results revealed that increased KIF15 expression in breast cancer tissues were positively related with tumor size, lymph node metastasis and TNM stage, and higher KIF15 expression predicts a worse prognosis of patients with breast cancer. Furthermore, KIF15 knockdown markedly attenuated breast cancer cell proliferation, migration, tumor growth and metastasis in vitro and in vivo, and silenced KIF15 expression significantly inhibited the expression of phosphorylated AKT, phosphorylated JNK, and cyclin D1, while both p53 and p21 protein expressions were strongly enhanced. These results suggest that KIF15 is a potential oncogene in human breast cancer.


Carcinoma in situ of the upper aerodigestive tract. Incidence, time trends, and follow-up in Rochester, Minnesota, 1935-1984.
Epidemiologic analyses of carcinoma in situ (CIS) of the upper aerodigestive tract (UAT) are virtually nonexistent. The current investigation summarizes the total UAT CIS experience of a white, middle class community from 1935 through 1984. Average annual incidence rates varied between genders (3.1 per 100,000 person-years for males versus 0.6 per 100,000 person-years for females), and increased from 1.5 to 3.1 lesions per 100,000 person-years between 1935 and 1964, and 1965 and 1984. Virgin CIS lesions represented 13% of all UAT carcinomas and the vermilion borders of the lips accounted for 42% of all UAT CIS cases. Age-specific incidence rates for males demonstrated a continuous increase with increasing age to 40.5 per 100,000 for males older than 75 years. A clinicopathologic analysis of these lesions is provided.


[Not Available].
The goal of the investigations was to determine the boundary conditions of compactness and hermetic level of covering material (permeability of the covering material) to inhibit mould growth during silage storage. The influence of air exclusion on fermentation quality, mould growth and mycotoxin content in the silage should be tested. To get a sufficient fermentation quality, as well as an inhibition of mould growth in the silages, necessary boundary conditions of air exclusion were: a compactness of at least 200-210 kg/DM m(3) and a maximum permeability of the covering material of 1,7 l/m(2) in 24 hours (six numbers of wraps of the used ensiling stretch film). Summarised, the measured amounts of <1,0 mg roquefortine C/kg in the silages is considered to be relatively low. Within the actual state of knowledge of toxicology, it is not considered dangerous to feed ruminat animals with silages containing these low amounts of roquefortin C.


The tumour-associated stroma correlates with poor clinical outcomes and immunoevasive contexture in patients with upper tract urothelial carcinoma: results from a multicenter real-world study (TSU-01 Study).
In this real-world study, we aimed to elucidate the predictive value of tumour-associated stroma for clinical prognostic and therapeutic response in upper tract urothelial carcinoma (UTUC) by reviewing the clinicopathologic characteristics of 1015 UTUC patients through a nationwide multicenter analysis. The tumour-stroma ratio (TSR) was assessed based on tissue sections stained for hematoxylin and eosin (H&E), and patients were further stratified into stroma-high (>50% stroma) and stroma-low group (≤50% stroma). Kaplan-Meier curve and Cox regression hazard analysis were conducted to assess the survival outcomes of UTUC patients. Bioinformatics analysis and immunostaining analysis were applied to portray the tumour microenvironment (TME). Stroma-high UTUC was significantly associated with poorer survival outcomes and inferior chemotherapeutic responsiveness. Our established nomogram achieved a high prognostic accuracy in predicting overall survival and cancer-specific survival in both of the discovery cohort (area under the curve [AUC] 0.663 and 0.712) and the validation cohort (AUC 0.741 and 0.747). Moreover, stroma-high UTUC was correlated with immunoevasive TME accompanied by increased cancer-associated fibroblasts, tumour-associated macrophages and, conspicuously a cluster of highly exhausted CD8+ T cells. Our results showed stroma-high UTUC was associated with an inferior prognosis and an immunoevasive TME with exhausted CD8+ T cells in UTUC patients. Our TSR-based nomogram could be used to refine prognosis and inform treatment decisions of patients with UTUC.


Personality profiles and meteoropathy intensity: A comparative study between young and older adults.
This study's main aims were to investigate the Big Five personality trait heterogeneity of study participants in two age groups and to examine whether these traits' heterogeneity can explain possible individual differences in meteoropathy intensity. The sample was comprised of 758 participants divided into two age groups: 378 young adults (18-30 years old) and 380 older adults (60+ years old). The participants filled out online or paper versions of the METEO-Q questionnaire and the Ten Item Personality Inventory (TIPI). A latent profile analysis of the completed inventories showed various personality profiles differ in meteoropathy intensity. However, personality's differentiating effect on meteoropathy was observed only among the young adult group. Our study's results indicate that there is no one personality trait pattern that fits all individuals regarding sensitivity to weather changes. This issue is especially visible when considering age differences.


Employability in people with epilepsy: A systematic review.
People with epilepsy were (PWE) reported to have poorer employment rate. However, the methodologies used differ greatly from one study to another, making global comparison difficult. We aimed to determine the employment rate of PWE globally using a unified definition of employment rate and to summarize the reported positive and negative factors affecting employability in PWE, using a systematic review. All studies reporting employment rate of PWE were independently assessed. Employment rate was recalculated according to the standard definition by the Bureau of Labor statistics (BLS) of United States and the International Labour Organization i.e. employment rate is the percentage of employed person over the labor force. Of 95 papers reported on employment status of PWE, adjusted employment rate (aER) was shown to be as low as 14% to as high as 89% with a mean adjusted employment rate of 58%. No significant differences in mean of aER was found between continents, or among Asian countries. Employment rate of people with uncontrolled seizures were reported in 16 papers, with a mean adjusted employed rate of 58%. Psychological factors were less frequently reported as compared to clinical and socio-demographical factors, seen in a total of 25 (26%) out of 97 studies. The positive factors leading to successful career in PWE were understudied and needed to be further explored. Employability is multifactorial, including clinical, psychological and social factors. The adjusted employment rate of people with uncontrolled seizures is comparable to those with controlled seizures, supporting the need to explore non-clinical factors.


[Detecting the API2-MALT1 fusion gene and its significance in Hashimoto's thyroiditis and thyroid lymphomas].
To investigate the expression of API2-MALT1 fusion gene mRNA in Hashimoto's thyroiditis, thyroid MALT lymphoma and DLBCL, as well as the correlation between the expression and the pathogenesis and prognosis of two types of thyroid lymphoma. Eight cases of Hashimoto's thyroiditis, 12 cases of MALT lymphoma and 3 cases of DLBCL in thyroid were selected and retrieved. API2-MALT1 transcripts were investigated in all cases by reverse transcript touchdown-PCR and nested PCR. The effect of API2-MALT1 fusion gene on the prognosis of thyroid lymphomas was assessed by analyzing the clinicopathological features and the follow-up findings. The variant 1446/1123 transcript was detected in 2 of thyroid lymphomas (1 MALT lymphoma, 1 DLBCL) but not in 8 cases of Hashimoto's thyroiditis and 5 cases of chronic lymphadenitis. Both of API2-MALT1-positive cases were accompanied with Hashimoto's thyroiditis, showing stage I E and no involvement of lymph node. The incidence of API2-MALT1 transcript in thyroid lymphomas was low; however, the correlation between API2-MALT1 fusion gene and the progression from Hashimoto's thyroiditis to lymphoma could not be excluded; the thyroid lymphoma with API2-MALT1 transcript seemed to develop on a more indolent clinical course.


[Updating in prescription of proton pump inhibitors. What to do and what not to do].
Proton pump inhibitors (PPIs) are the most prescribed pharmacological subgroup of the National Health System and their use has been related to possible potentially serious adverse effects. To review the current indications for treatment with PPIs as well as the data related to their safety, in order to promote their adecuate use. A review of the literature focused on the following topics has been carried out: a) molecules and mechanism of action; b) current indications for treatment and adherence to them; c) adverse effects related to its use; d) drug interactions; e) alternatives in deprescription. The current indications have not changed substantially in recent years and are well established, however, there is a high percentage of inappropriate prescription, mainly in individuals with low or no risk. PPIs are safe drugs and generally well tolerated and their benefits are higher than possible adverse effects. Adhering to evidence-based recommendations represents the only rational approach to safe and effective therapy.


Motor Variability Prior to Learning does not Facilitate the Ability to Adopt new Movement Solutions.
Many contexts in motor learning require a learner to change from an existing movement solution to a novel movement solution to perform the same task. Recent evidence has pointed to motor variability prior to learning as a potential marker for predicting individual differences in motor learning. However, it is not known if this variability is predictive of the ability to adopt a new movement solution for the same task. Here, we examined this question in the context of a redundant precision task requiring control of motor variability. Fifty young adults learned a precision task that involved throwing a virtual puck toward a target using both hands. Because the speed of the puck depended on the sum of speeds of both hands, this task could be achieved using multiple solutions. Participants initially performed a baseline task where there was no constraint on the movement solution, and then performed a novel task where they were constrained to adopt a specific movement solution requiring asymmetric left and right hand speeds. Results showed that participants were able to learn the new solution, and this change was associated with changes in both the amount and structure of variability. However, increased baseline motor variability did not facilitate initial or final task performance when using the new solution - in fact, greater variability was associated with higher errors. These results suggest that motor variability is not necessarily indicative of flexibility and highlight the role of the task context in determining the relation between motor variability and learning.


Transcriptional memory of cells of origin overrides β-catenin requirement of MLL cancer stem cells.
While β-catenin has been demonstrated as an essential molecule and therapeutic target for various cancer stem cells (CSCs) including those driven by MLL fusions, here we show that transcriptional memory from cells of origin predicts AML patient survival and allows β-catenin-independent transformation in MLL-CSCs derived from hematopoietic stem cell (HSC)-enriched LSK population but not myeloid-granulocyte progenitors. Mechanistically, β-catenin regulates expression of downstream targets of a key transcriptional memory gene, Hoxa9 that is highly enriched in LSK-derived MLL-CSCs and helps sustain leukemic self-renewal. Suppression of Hoxa9 sensitizes LSK-derived MLL-CSCs to β-catenin inhibition resulting in abolishment of CSC transcriptional program and transformation ability. In addition, further molecular and functional analyses identified Prmt1 as a key common downstream mediator for β-catenin/Hoxa9 functions in LSK-derived MLL-CSCs. Together, these findings not only uncover an unexpectedly important role of cells of origin transcriptional memory in regulating CSC self-renewal, but also reveal a novel molecular network mediated by β-catenin/Hoxa9/Prmt1 in governing leukemic self-renewal.


First comparative assessment of contamination by plastics and non-synthetic particles in three bivalve species from an Italian sub-alpine lake.
This study aimed to compare the contamination from plastics and non-synthetic particles in the three freshwater bivalve mollusks Unio elongatulus, (native) and Corbicula fluminea and Dreissena polymorpha (invasive), collected in Lake Maggiore, the second greatest Italian lake. Organisms were collected from eight sites located throughout the lake, during three years (2019-2021). The quali-quantitative characterization of particles has been carried out using a Fourier Transform Infrared Microscope System (μFT-IR). Results showed that both plastics and non-synthetic particles released in the water are taken up by bivalves, even though low intake-up to 6 particles/individuals-were measured for all the three species. Microfibers of both synthetic (polyester, polyamide) and natural (cellulose) origin represented the particles mostly ingested by bivalves. A significant decrease of particle loads was observed in 2020 with respect to 2019 and 2021, significantly different for D. polymorpha and U. elongatulus, suggesting a transient reduction of the particle release in the lake in this year. Our findings highlight the need to improve the understanding of the mechanisms of uptake and clearance of these contaminants by filter feeding organisms, and their adverse consequences in realistic environmental conditions.


Distributed algorithms over communicating membrane systems.
This paper presents fundamental distributed algorithms over membrane systems with antiport carriers. We describe distributed algorithms for collecting and dispersing information, leader election in these systems, and the mutual exclusion problem. Finally, we consider membrane systems producing correct results despite some failures at some of the components or the communication links. We show that membrane systems with antiport carriers provide an appropriate model for distributed computing, particularly for message-passing algorithms interpreted here as membrane transport in both directions, namely when two chemicals behave as input and output messages and pass the membranes in both directions using antiport carriers.


High-dose strategies for managing phosphine-resistant populations of Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae).
Rhyzopertha dominica is a serious pest of stored grains and many populations have resistance to the fumigant phosphine. Some populations contain beetles with a 'strong resistance' phenotype. Recent work found the LC50 values for two strong-resistant populations recently studied in North America, Belle Glade and Minneapolis were 100- and 595-fold higher, respectively, compared to LC50 of a lab-susceptible strain. Populations with 'weak-resistant' phenotypes had LC50 values 5- to 10-fold that of a susceptible strain. The work reported below aimed to determine the minimum phosphine concentrations and number of days of exposure needed to effectively control all life stages of representative weak- and strong-resistant strains, and then to recommend the treatment conditions needed to control strongly phosphine-resistant R. dominica in pest populations. A dose-mortality assay estimated that phosphine fumigation over 48 h using 730-870 ppm at 25° C would control adults of both strongly resistant R. dominica populations. Fumigations with mixed life stage cultures found 200 ppm killed all susceptible and weak-resistant beetles in 2 days, but the strong-resistant Minneapolis and Belle Glade strains had substantial survivors at 200 ppm. Furthermore, the Belle Glade strain had beetles that survived 1000 ppm in 2-day fumigations. The strong-resistant Belle Glade strain needed nearly 10 days at over 400 ppm to have acceptable levels of control. This study recommends protocols to manage strongly resistant R. dominica populations provided that a minimum phosphine concentration of 400 ppm be maintained at 25° C or higher for up to 10 days. © 2019 Society of Chemical Industry.


Phosphodiester CpG oligonucleotides as adjuvants: polyguanosine runs enhance cellular uptake and improve immunostimulative activity of phosphodiester CpG oligonucleotides in vitro and in vivo.
Bacterial DNA and oligonucleotides (ODN) containing CpG-motifs strongly activate cells of the immune system. Accordingly CpG-DNA is a powerful adjuvant in vaccination protocols for B-cell as well as for cytotoxic T-cell responses. A decisive propensity of CpG-DNA is its capacity to induce preferentially T helper type 1 (Th1)-dominated immune responses. To exert its function CpG-DNA has to be taken up by responsive cells, e.g. antigen-presenting cells (APC). The rate of uptake is influenced by the DNA's backbone modification and critically determines activity of CpG-DNA. CpG ODN with a phosphothioate backbone (PTO) are currently used for most in vivo and in vitro studies, since PTO modification protects ODN from the attack of nucleases. However, after administration of PTO-modified CpG-ODN long-lasting effects including lymphadenopathy as well as sustained local interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) production have been reported. To circumvent these restrictions we investigated the effects of DNA sequence as well as DNA backbone modification on cellular uptake and resulting immunostimulation. We show here that uptake of phosphodiester (PO)-CpG-ODN can be strongly enhanced by poly guanosine runs added at the 3' end of the ODN. In addition these ODN showed an improved immunostimulatory activity in vivo and in vitro. This included protection of mice against lethal Th2-dependent leishmaniasis as well as priming of antigen specific Th1 responses. More importantly, guanosine-rich PO-CpG-ODN neither induced lymphadenopathy nor prolonged cytokine production after local administration. Since these improved PO ODN are efficient in vitro and in vivo and lack long lasting undesired effects they could be used preferably as adjuvants in vaccination protocols.


Transplantation of PC1/3-Expressing alpha-cells improves glucose handling and cold tolerance in leptin-resistant mice.
Type 2 diabetes (T2D) is characterized by elevated blood glucose levels owing to insufficient secretion and/or activity of the glucose-lowering hormone insulin. Glucagon-like peptide-1 (GLP-1) has received much attention as a new treatment for diabetes because of its multiple blood glucose-lowering effects, including glucose-dependent enhancement of insulin secretion, inhibition of gastric emptying, and promotion of the survival and growth of insulin-producing beta-cells. GLP-1, along with GLP-2 and oxyntomodulin, is produced in the intestinal L-cell via processing of proglucagon by prohormone convertase 1/3 (PC1/3), while in the pancreatic alpha-cell, coexpression of proglucagon and the alternate enzyme PC2 typically results in differential processing of proglucagon to yield glucagon. We used alginate-encapsulated alpha-cells as a model to evaluate continuous delivery of PC1/3- or PC2-derived proglucagon products. In high fat-fed and db/db mice, PC1/3-, but not PC2-expressing alpha-cells improved glucose handling and transiently lowered fasting glucose levels, suggesting that continuous delivery of PC1/3-derived proglucagon products via cell therapy may be useful for diabetes treatment. In addition, we show that long-term treatment with PC1/3-expressing, but not PC2-expressing, alpha-cells improved cold-induced thermogenesis in db/db mice, demonstrating a previously unappreciated effect of one or more PC1/3-derived alpha-cell products.


Enantioselective Rauhut-Currier-Type 1,6-Conjugate Addition of Methyl Vinyl Ketone to para-Quinone Methides.
An unprecedented Rauhut-Currier-type 1,6-conjugate addition has been developed. With chiral cyclohexane-based phosphine-amide catalyst 3 h, the 1,6-conjugate reaction has been achieved to produce chiral diarylmethine compounds in excellent yields (91-99 %) and enantioselectivities (92-98 % ee).


Expression of FK506-binding protein 51 (FKBP51) in Mycosis fungoides.
Mycosis fungoides (MF) is the major subtype of cutaneous T-cell lymphomas (CTCL). It usually has a prolonged indolent clinical course with a minority of cases acquiring a more aggressive biological profile and resistance to conventional therapies, partially attributed to the persistent activation of nuclear factor-kappa B (NF-κB) pathway. In the last decade, several papers suggested an important role for the FK506-binding protein 51 (FKBP51), an immunophilin initially cloned in lymphocytes, in the control of NF-κB pathway in different types of human malignancies. We aimed to investigate the possible value of FKBP51 expression as a new reliable marker of outcome in patients with MF. We assessed by immunohistochemistry (IHC) FKBP51 expression in 44 patients with MF, representative of different stages of the disease. Immunohistochemical results were subsequently confirmed at mRNA level with quantitative PCR (qPCR) in a subset of enrolled patients. In addition, IHC and qPCR served to study the expression of some NF-κB-target genes, including the tumour necrosis factor receptor-associated factor 2 (TRAF2). Our results show that FKBP51 was expressed in all evaluated cases, with the highest level of expression characterizing MFs with the worst prognosis. Moreover, a significant correlation subsisted between FKBP51 and TRAF2 IHC expression scores. We hypothesize a role for FKBP51 as a prognostic marker for MF and suggest an involvement of this immunophilin in deregulated NF-κB pathway of this CTCL.


Diethylstilbestrol impaired oogenesis of yellow catfish juveniles through disrupting hypothalamic-pituitary-gonadal axis and germ cell development.
Diethylstilbestrol (DES), a non-steroidal estrogen, has been found to cause altered germ cell development and disordered ovarian development in fish females. However, the mechanisms that might be involved are poorly understood. In this study, female juveniles of yellow catfish (Pelteobagrus fulvidraco) (120 days post-hatching) were exposed to two doses (10 and 100 ng l-1 ) of DES for 28 days. After the endpoint of exposure, decreased ovary weight and gonadosomatic index, as well as various ovarian impairments were observed in response to DES. Besides, DES elevated the mRNA levels of vitellogenin 1 (vtg 1) and estrogen receptor 1 (esr 1) in liver and decreased 17β-estradiol level in plasma. Correspondingly, suppressed mRNA levels of the key genes in the hypothalamic-pituitary-gonadal axis (such as cyp19a1b, gnrh-II, fshβ and lhβ in brain and fshr, lhr and cyp19a1a in ovary) after DES exposure were also observed. The declined level of plasma 17β-estradiol and altered gene expressions of genes in the hypothalamic-pituitary-gonadal axis were thus supposed to be closely related to the disrupted oogenesis in DES-treated fish. Analyses further demonstrated that, higher concentration of DES elevated the expression ratio of bax/bcl-2, indicating the enhanced apoptosis occurred in ovary. Moreover, DES upregulated the expressions of genes involved in proliferation (cyclin d1 and pcna), meiotic entry (cyp26a1 and scp3) and meiotic maintenance (dmc1), resulting in arrested oogenesis in catfish. The present study greatly extended our understanding on the mechanisms underlying of reproductive toxicity of DES on fish oogenesis.


Patterns of Growth and Nutrition From Birth to 6 Months in Infants With Complex Congenital Cardiac Defects.
Infants with complex congenital heart defects (CCHDs) experience alterations in growth that develop following surgical intervention and persist throughout early infancy, but the roles of nutritional intake and method of feeding require further exploration as their roles are not fully explained. The purpose of this study was to characterize trends in growth and nutritional intake during the first 6 months of life in infants with CCHD. We conducted a secondary analysis of growth and nutritional data from a pilot study designed to test the feasibility of nurse-guided participatory intervention with parents of infants with CCHD. Measures included demographic data, anthropometric data at birth, hospital discharge, and 6 months of age, nutritional intake at 2 and 6 months of age from parent-completed 24-hour nutrition diaries, and assessment of oral-motor skills between 1 and 2 months of age. Descriptive statistics and correlation and group differences were examined. Data for 28 infants were analyzed. Infants demonstrated a decrease in weight-for-age z score (WAZ) and length-for-age z score (LAZ) from birth to hospital discharge and an increase in WAZ and LAZ by 6 months of age. Many of the infants developed failure to thrive. Across the study period, one third of the infants were receiving enteral nutrition. Infants who were orally fed had better growth WAZ and LAZ at 6 months of age when compared to infants who were enterally fed. Infants with CCHD exhibit growth faltering throughout early infancy. Reliance on enteral nutrition did not improve growth outcomes in these infants. Findings suggest nutritional intake may not be enough to meet the nutrient requirements to stimulate catch-up growth.


Immunity to Babesia in mice. III. The effects of corticosteroids and anti-thymocyte serum on mice immune to Babesia rodhaini.
BALB/c mice, immunized against Babesia rodhaini by an amicarbalide controlled infection, were exposed to selective immunosuppressive treatment with corticosteroids and anti-thymocyte serum (ATS) respectively. Hydrocortisone acetate, 100 mg/kg, given i.p. six times during the three weeks after challenge inoculation caused a rising parasitaemia and high mortality (6/7). Dexamethasone in the drinking water at 20 mg/l or 10 mg/l for 22 days had a similar suppressive effect on the protection against B. rodhaini. Mortality, 100% at the dose rate of 20 mg/l and 50% at 10 mg/l, occurred both in challenged and in carrier animals after the reappearance of parasites in the bloodstream. All the ATS-treated immune mice demonstrated parasitaemia after challenge, although at a lower level than did the corticosteroid treated mice. Seven out of 9 animals died. Corticosteroid-sensitive macrophages together with T-lymphocytes are considered to play an important role in protection against B. rodhaini in specifically induced immunity in mice.


'Our hands are bound': Pathways to community health labour in Kenya.
An ideal model of Community Health Worker (CHW) selection has existed since long before Alma Ata catalysed the community health approach, dating to late colonial times. In this model, a willing, trusted, relatively well-educated and secure member of the community with proven aptitude is openly elected by their leadership, peers or relevant committee. Their participation is entirely voluntary and that voluntarism is symbolic of their community's participation as a whole. While this imagery is long-embedded in CHW storytelling, such practice is rare. While elements of this 'model pathway' exist, a myriad of structural and agential factors shape who becomes a CHW, how and why. Through life history interviews over twelve months 2022-2023 with 68 CHWs in Isiolo, northern Kenya (known as CHVs), we explore predominant pathways to community health labour as told through stories. We articulate five such pathways: model, handpicked, shadow, outsider and, most importantly, dispossession. Through telling five CHVs' stories, we present each 'ideal type' but also explore how each pathway is not singular, rather overlapping in complex, context-specific ways. These pathways confound Western-centric, Western-promoted notions of voluntarism and indeed community health, which cannot explain why such labour endures. We conclude that our findings provide a timely commentary on how voluntary labour within health continues to tax structural poverty and frustrated life chances in lieu of concrete and expansive investments in human resources for health by governments and health agencies both North and South. In understanding voluntary labour as a form of structural violence, we can better elucidate the historical dependency on this work in impoverished regions and how the undervaluing of such work persists over time.


Karaya gum-graft-poly(2-(dimethylamino)ethyl methacrylate) gel: An efficient adsorbent for removal of ionic dyes from water.
In the present study, a novel hydrogel based on the polysaccharide, 'Karaya gum' has been synthesised by graft copolymerization and evaluated as an adsorbent for the removal of ionic dyes from aqueous solution. The hydrogel was made by simultaneous grafting and cross linking of Karaya gum using 2-(dimethylamino)ethyl methacrylate (DMAEMA) and N,N'-methylene-bis-acrylamide via microwave irradiation. The graft copolymer gel was characterized by FTIR, TGA, SEM techniques. The swelling of the gel studied in buffer media of varying pH revealed a pH responsive behaviour with a maximum swelling in neutral pH and a minimum swelling at pH 1.2. The temperature dependent swelling study indicated 40 °C as the lowest critical solution temperature. Kinetic studies indicated the swelling to be a second order process with Fickian diffusion as the water transport mechanism. The adsorption studies indicated maximum adsorption capacity of 89.28 and 101.42 mg/g towards methylene blue and indigo carmine respectively. The dye adsorption data is found to fit well with pseudo- second order kinetic model and the Freundlich adsorption isotherm model. The adsorption was found to be a multistep process with surface adsorption followed by intraparticle diffusion. Thermodynamic studies revealed the adsorption of dyes to be spontaneous.


Specific cytosol-binding protein for 1,25-dihydroxyvitamin D3 in rat intestine.
Cytosol prepared from intestinal homogenates of vitamin D3-deficient rats demonstrate a 3.2 S protein having high affinity and low capacity for 1,25-dihydroxyvitamin D3. Appearance of the protein is dependent upon the presence of 0.3 M potassium chloride and dithiothreitol in the homogenization buffer. A 6 S protein having greater affinity for 25-hydroxyvitamin D3 than 1,25-dihydroxyvitamin D3 is observed using all conditions and is increased by the addition of rat serum to cytosol. The 3.2 S protein is neither a serum contaminant nor a component of the 6 S protein and is probably not a consituent of tissues which which are not responsive to vitamin D3.


Chloroplast biogenesis. Net synthesis of protochlorophyllide from magnesium-protoporphyrin monoester by developing chloroplasts.
Developing chloroplasts were isolated from greening Cucumis cotyledons in a cofactor-enriched medium and were incubated in the dark with 14C-labeled and unlabeled magnesium-protoporphyrin monoester. The metabolic pools between protoporphyrin and protochlorophyllide were monitored spectrofluorometrically. The incorporation of the 14C label into protochlorophyllide was also determined. It was shown that magnesium-protoporphyrin monoester, a postulated intermediate of the chlorphyll biosynthetic pathway, was convertible into protochlorophyllide with relatively high yields. Since protochlorophyllide is the immediate precursor of chlorophyll a it was concluded that magnesium-protoporphyrin monoester was indeed an intermediate of the chlorophyll biosynthetic pathway.


Natural History of Nonhuman Primates After Oral Exposure to Ebola Virus Variant Makona.
The primary route of infection by Ebola virus (EBOV) is through contact of mucosal surfaces. Few studies have explored infection of nonhuman primates (NHPs) via the oral mucosa, which is a probable portal of natural infection in humans. To further characterize the pathogenesis of EBOV infection via the oral exposure route, we challenged cohorts of cynomolgus monkeys with low doses of EBOV variant Makona. Infection with 100 or 50 PFU of EBOV Makona via the oral route resulted in 50% and 83% lethality, respectively. Animals that progressed to fatal disease exhibited lymphopenia, marked coagulopathy, high viral loads, and increased levels of serum markers of inflammation and hepatic/renal injury. Survival in these cohorts was associated with milder fluctuations in leukocyte populations, lack of coagulopathy, and reduced or absent serum markers of inflammation and/or hepatic/renal function. Surprisingly, 2 surviving animals from the 100- and 50-PFU cohorts developed transient low-level viremia in the absence of other clinical signs of disease. Conversely, all animals in the 10 PFU cohort remained disease free and survived to the study end point. Our observations highlight the susceptibility of NHPs, and by extension, likely humans, to relatively low doses of EBOV via the oral route.


Adolescents, parents and teachers' perceptions of risk and protective factors of substance use in Moroccan adolescents: a qualitative study.
Substance use in adolescents is a global public health concern that continues to draw attention from academics, policy experts, and government officials. In Morocco, few studies have investigated the influencing factors of substance use in adolescents. Here, we aimed to fill this gap and to better understand factors that protect or influence substance use in adolescents. We conducted a qualitative study using focus group discussions. The semi-structured interview guides were based on the socio-ecological model as a theoretical framework to explore perceptions of students, parents, and teachers regarding substance use risks and protective factors in adolescents. Data from each group were audio-recorded, transcribed, and analyzed using thematic analysis. From May to July 2016, 17 focus group discussions were conducted at two middle schools in Taza city, Morocco, which included 8 groups of 7 adolescents (28 boys and 28 girls) aged 14 to 16 years, 5 groups of parents (5 females and 21 males), and 4 groups of teachers (13 males and 5 females). Thematic analysis resulted in six common themes that represented the most salient perceived risk and protective factors regarding substance use among adolescents: perceived benefits of substance use, awareness and beliefs, family influence, peer influence, easy accessibility of substances, and social norms. Our results demonstrate that multilevel prevention programs in adolescents should address influencing factors from the individual to the societal level, including social norms and the government's policy toward substance use. Health education programs included as part of the school curriculum can contribute to promoting awareness and reducing risky behaviors of Moroccan adolescents.


The clinical implications of triple therapy in fixed-dose combination in COPD: from the trial to the patient.
The emergence of a fixed-dose combination (FDC) of a long-acting ß2-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled corticosteroid (ICS) in a single inhalation device has changed the approach to inhaled therapy. Although clinical trials describe the efficacy and safety of these FDCs, their use in daily clinical practice can present challenges for the clinician in two specific scenarios. In patients who are already receiving triple therapy via different devices, switching to FDCs could confer benefits by reducing critical errors in the management of inhalers, improving therapeutic adherence, and lowering costs, while maintaining the same clinical efficacy. In patients who are not receiving triple therapy in different devices and who require a change in treatment, triple therapy FDC has shown benefits in clinical trials. Although methodological differences among the trials advise against direct comparison, clinical results show good efficacy, but also considerable variability, and a number of clinical outcomes have yet to be explored. In the future, trials must be developed to complete clinical efficacy data. Real-world efficacy trials are needed, and studies must be designed to determine the profile of patients who present a greater therapeutic response to each FDC in order to pave the way towards more personalized treatment.


Patient and proxy measurement of quality of life among general hospital in-patients with dementia.
We aimed to investigate quality of life ratings among people with varying severity of dementia and their carers, recruited in general hospital. We recruited 109 people with dementia, and their proxies (carers), from psychiatric referrals of inpatients in two general hospitals in England. From patients, we gathered data on quality of life (QoL-AD and EQ5-D) and depressive symptoms, and from proxies we gathered data on patient quality of life (Proxy QoL-AD and EQ5-D), severity of dementia, activities of daily living, physical illness and depressive symptoms, and on carer stress. Completion rates for both measures were progressively lower with increasing dementia severity. Patients rated their quality of life more highly than proxies on Qol-AD (patients=32.2, CI=30.7-33.7, proxies=24.7, CI=23.8-26.0, p<0.001) and on EQ5D (patients=0.71, CI=0.64-0.77, proxies=0.30, CI=0.22-0.38, p<0.001). For proxy EQ5D, impaired instrumental ADLs (p=0.003) and more severe dementia (p=0.019) were associated with ratings, while for proxy QoL-AD, only more severe dementia (p=0.039) was associated with ratings. Lower patient EQ-5D scores were independently associated only with carer stress (p=0.01). Lower patient QoL-AD scores were associated with patient depression (p=0.001), impaired activities of daily living (p=0.02) and proxy psychiatric symptoms (p=0.002). Among patients with moderate to severe dementia in general hospital, proxy measures of quality of life are the only practical option. Patients and proxies appear to have very different concepts of quality of life in dementia.


Absence of linkage to 8q23.3-q24.1 and 2p11.1-q12.2 in a new BAFME pedigree in China: indication of a third locus for BAFME.
Benign adult familial myoclonic epilepsy (BAFME) were mapped on chromosome 8q24 and 8q23.3-q24.1 in Japanese pedigrees and mapped on 2p11.1-2q12.2 in European pedigrees, respectively. Recently, we recruited a large BAFME pedigree in China. After genotyping 11 microsatellite markers covering the two previously identified chromosome regions, we performed linkage analyses. However, evidence of negative linkage was found in the two previously reported candidate regions (LOD score <-3.0 at no recombination). Our data suggest that the causative gene responsible for BAFME in the Chinese pedigree may be located on a new region other than 8q23.3-q24.1 and 2p11.1-q12.2, indicating the presence of a third locus for BAFME.


Propoxyphene and acetaminophen. Possible effects on the fetus.
Propoxyphene (Darvon) and acetaminophen (Tylenol) are widely prescribed analgesic agents. Both can cross the placenta, and propoxyphene can produce serious withdrawal symptoms in newborns. Neither propoxyphene nor acetaminophen is considered a teratogen, yet, three malformed infants who were antenatally exposed to propoxyphene have previously been reported. We report a fourth case of an infant, with withdrawal symptoms and cranial-facial and digital malformations, born to a women who used propoxyphene and acetaminophen throughout her pregnancy. We suggest that possibility that the antepartum use of propoxyphene and acetaminophen, in combination, may be teratogenic.


Excretory-Secretory Products of Trichomonas vaginalis Cause Apoptosis in Mouse Sperm in Vitro.
Excretory-secretory products (ESP) of T. vaginalis have been shown to inhibit sperm motility, viability, and functional integrity, leading to a decreased fertilization rate in vitro. This study investigated whether T. vaginalis induce apoptosis and ultrastructural changes of sperm using flow cytometry and electron microscopy. Incubation of sperm with T. vaginalis ESP increased phosphatidylserine externalization and DNA fragmentation, and decreased mitochondrial membrane potential. Transmission electron microscopy of sperm incubated with ESP revealed abnormal features such as distorted heads, broken necks, and acrosomes exocytosis. This is the first report that demonstrates a direct impact of T. vaginalis ESP on sperm apoptosis and architecture in vitro.


Energy loss for evaluating heart valve performance.
Energy loss is a well-established engineering concept that when applied to evaluating the performance of native heart valves and valvular prostheses has the potential for providing valuable information about the impact of valve function on myocardial performance. The concept has been understood for many years, but its routine application has been hindered not only by a lack of understanding of its meaning but also because of the lack of investigational tools to easily obtain the data necessary for its estimation. Today the gathering of that information is becoming easier, and thus the time has come to revisit the efficacy of energy loss for evaluating heart valve performance. This review defines what energy loss is, how it is measured, and how it might be applied to clinical situations of heart valve disease to better understand the impact of valvular disease on ventricular function.


IMPlicating Mesenchymal Imp1 in Colitis-Associated Cancer.
Chronic inflammation and associated pathways are significant facilitators of many disease states, including malignancies. In the context of cancer, fibroblasts can actively regulate both inflammation and carcinogenesis. In this issue, Hamilton and colleagues describe a fibroblast-specific role of the RNA binding protein Imp1 in suppression of intestinal inflammatory responses and development of colitis-associated cancer.


Increasing the evidence base for selection for undergraduate medicine: four case studies investigating process and interim outcomes.
Prior to 1997, the University of Adelaide, Australia selected medical students according to matriculation marks alone. After extensive consultation with relevant stakeholders and examination of empirical evidence, the selection process is now based on a national written examination of reasoning and interaction skills, a structured oral assessment and a threshold matriculation score. This paper presents a series of 4 case studies examining the process related to the procedure and early interim outcomes, with the aim of adding to the evidence base for methods of medical student selection. Data were collected from a range of sources between 1996 and 2001, including the University's central administration system, the Faculty of Health Sciences, and purpose-designed oral assessment forms and self-report student questionnaires. The oral assessment process has shown itself to be characterised by a high level of interassessor reliability. Equity of access has been addressed and the number of schools represented in the student intake has increased from between 10 and 15 in the final years of the old selection process to over 30 statewide under the new process. There has been a corresponding increase in the proportion of students from rural backgrounds (from an original 4-12% to 20-22%). These investigations add to the evidence base for medical school selection in that they demonstrate that an oral assessment process can be reliable and lead to early positive results in relation to student outcomes and access.


Auricular cartilage palisade tympano-, epitympano-, antrum- and mastoid-plasties.
Autogenous auricular cartilage and perichondrium have been used to reconstruct the tympanic membrane and ossicular chain. The variations of technique are described.


Bivalent COVID-19 mRNA booster vaccination (BA.1 or BA.4/BA.5) increases neutralization of matched Omicron variants.
We report SARS-CoV-2 neutralizing antibody titers in sera of triple-vaccinated individuals who received a booster dose of an original monovalent or a bivalent BA.1- or BA.4/BA.5-adapted vaccine or had a breakthrough infection with Omicron variants BA.1, BA.2 or BA.4/BA.5. A bivalent BA.4/BA.5 booster or Omicron-breakthrough infection induced increased Omicron-neutralization titers compared with the monovalent booster. The XBB.1.5 variant effectively evaded neutralizing-antibody responses elicited by current vaccines and/or infection with previous variants.


PCD1, a novel gene containing PDZ and LIM domains, is overexpressed in human breast cancer and linked to lymph node metastasis.
Despite surgical removal of the primary tumor of breast cancer in patients with apparently localized disease, relapse at local or distant sites may occur because undetectable micrometastases were present at the time of diagnosis. Identification of molecules associated with breast cancer metastasis suggests possible new treatments. PCD1, a gene encoding a new member of the PDZ and LIM domain-containing protein family, recently was identified. We examined the relationships between PCD1 mRNA expression in breast cancers and metastasis. PCD1 mRNA expression in breast cancer tissues was examined using a quantitative reverse transcription polymerase chain reaction. PCD1 mRNA expression was greater in cancers than in noncancerous tissues (p < 0.0001). In addition, high PCD1 gene expression was more frequent in patients with lymph node metastasis. PCD1 appears to contribute to breast cancer progression and nodal metastasis, thus representing a potential target molecule in breast cancer diagnosis and treatment.


Postmortem findings in COVID-19 fatalities: A systematic review of current evidence.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). Almost 17 months after the first COVID-19 case was reported, the exact pathogenesis of the virus is still open to interpretation. Postmortem studies have been relatively scarce due to the high infectivity rate of the virus. We systematically reviewed the literature available for studies that reported gross, histological, microscopic, and immunohistochemical findings in COVID-19 fatalities with the aim of reporting any recurrent findings among different demographics. PubMed and Scopus were searched up till the second of May 2021 and 46 studies with a total of 793 patients were shortlisted after the application of inclusion and exclusion criteria. The selected studies reported gross, histological, microscopic, and immunohistochemical autopsy findings in the lungs, heart, liver, gallbladder, bowels, kidney, spleen, bone marrow, lymph nodes, CNS, pancreas, endocrine/exocrine glands, and a few other miscellaneous locations. The SARS-CoV-2 virus was detected in multiple organs and so was the presence of widespread microthrombi. This finding suggests that the pathogenesis of this highly infectious virus might be linked to some form of coagulopathy. Further studies should focus on analyzing postmortem findings in a larger number of patients from different demographics in order to obtain more generalizable results.


Dietary energy density is favorably associated with dietary diversity score among female university students in Isfahan.
To report the relation between dietary energy density and dietary diversity score (DDS) in Isfahanian female university students. This cross-sectional study was conducted in 289 healthy females who were randomly chosen by a cluster random sampling method from among students at Isfahan University of Medical Sciences, Isfahan, Iran. A validated semiquantitative food-frequency questionnaire was used to assess the usual dietary intake. Dietary energy density was calculated as an individual's reported daily energy intake (kilocalories per day) per total weight of foods (excluding beverages) consumed (grams per day). The DDS was calculated based on the scoring of the five food groups of the Food Guide Pyramid. The mean dietary energy density was 1.60 ± 0.29 kcal/g. Individuals in the top tertile of dietary energy density had the lowest mean DDS (means among tertiles: first, 9.61 ± 1.92; second, 6.98 ± 1.22; third, 3.63 ± 1.02; P < 0.05) and diversity scores of vegetables (1.91 ± 0.33, 1.54 ± 0.26, 1.11 ± 0.2, P < 0.01) and fruit (1.98 ± 0.72, 1.89 ± 0.66, 1.44 ± 0.3, P < 0.05). Those in the top tertile of the DDS had the lowest mean dietary energy density (2.08 ± 0.36, 1.69 ± 0.31, 1.38 ± 0.25 kcal/g, P < 0.05). There was an inverse and significant association between dietary energy density and DDS (r = -0.3, P = 0.03). There was inverse significant association between the DDS and dietary energy density in Isfahanian female university students. Further prospective investigations will be needed to confirm this finding.


Cheaper drugs and techniques to fulfill chief executive officer perspectives - any choices?
Against the background of increasing healthcare costs and diminishing budgets, this review aims to present clinicians with ethically viable options to overcome budgetary restraints when seeking to introduce novel products. Healthcare administrators and primary healthcare providers are not unlikely to have different opinions when discussing the introduction of novel products. However, rather than taking a 'no' for an answer, doctors may be able to argue for a change - even if this may seem to come at a higher cost. The recent introduction of the reversal agent sugammadex may provide a timely example for the possibility of success 'against all financial odds'. Health professionals have the responsibility to deliver high-quality care while acknowledging the financial budget constraints. However, evidence (vs. perception) for outcome benefits of novel drugs or devices should stimulate a robust desire for their timely introduction. Demonstrating actual benefits understandable to administrators, seeking alliances with other medical specialties or patient groups, as well as negotiations with the healthcare industry may all represent viable options. Simply waiting for patents to expire should remain a measure of last resort.


Effect of folic acid on the postharvest physiology of broccoli during storage.
The objective of the present study was to explore the effect of folic acid on the postharvest physiology of broccoli placed in storage. Broccoli heads were immersed in 5 mg L-1 folic acid for 10 min, then stored at 20 ± 1 °C for 4 days. Results indicated that the postharvest treatment of broccoli with folic acid decreased the rate of flower opening and yellowing, inhibited weight loss, reduced the level of respiration, as well as ethylene generation. Folic acid-treated broccoli maintained their level of chlorophyll, total soluble solids, vitamin C, total phenolics, flavonoids, glucosinolate, and folic acid. Treated broccoli also exhibited reduced accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS). Concomitantly, antioxidant enzyme activity and corresponding gene expression were also enhanced. In contrast, chlorophyll-degrading enzyme gene expression was suppressed. These results indicated that folic acid treatment of broccoli could be used to prolong shelf-life.


Tissue culture of the retinal pigment epithelial cells.
Pure culture of the retinal pigment epithelial (RPE) cells of the chick embryo was carried out and the morphological characteristics of each developmental stage were observed under light microscope and transmission and scanning electron microscopes. Immature cells had a few, short processes on the apical surface and a few melanin granules in the cytoplasm. However, mature cells had two types of processes on the apical surface, one being narrow and the other wide. Many melanin granules were diffusely dispersed in the cytoplasm and the cells were joined by a junctional complex near the apical portion. Beneath the cultured cells, basement membrane and collagen fibrils were evident and were apparently produced by the culture RPE cells. The structure of the cultured cells in the well-differentiated stage appeared to be the same as that of living cells.


Preparatory postural adjustments during gait initiation in healthy younger and older adults: Neurophysiological and biomechanical aspects.
The most postural adjustments studies have focused on electromyographic and biomechanical events to identify the mechanisms involved in falling, whereas direct recording of central processor system could be an optimal approach to provide new insights into this field. Therefore, the purpose of this study was to determine neurophysiological and biomechanical aspects of the preparatory postural adjustments during gait initiation (GI) in healthy younger and older adults. 16 healthy younger and 15 healthy older adults participated in the study. Stimuli of warning and response were played with an inter-stimulus interval of 2s and subjects were instructed to begin forward stepping with the dominant limb in response to response stimulus. The contingent negative variation (CNV), onset time of electromyographic activity in leading limb muscles and center of pressure (COP) trajectory in the anticipatory phase of GI were measured. Results revealed the peak time of CNV and mean amplitude of Late CNV were earlier and smaller in older group, respectively. However, peak amplitude of CNV did not differ significantly between groups. Moreover, the older group exhibited a delayed onset activity of gluteus medius and tibialis anterior muscles as well as a slower velocity and lesser backward displacement of COP trajectories in comparison with the younger group. Additionally, there were strong relationships between neurophysiological and biomechanical parameters. Findings suggest the age-related changes in the brain activities and preparatory postural adjustments during GI which could be valuable in designing assessment and prevention approaches for falls in this group of people.


Pharmacokinetics and safety of a raltegravir-containing regimen in HIV-infected children aged 2-12 years on rifampicin for tuberculosis.
Drug-drug interactions limit current antiretroviral treatment options for HIV-infected children with tuberculosis (TB). Rifampicin (RIF) induces UDP-glucuronosyltransferase activity, accelerating the clearance of raltegravir (RAL). We sought to establish an optimal and well tolerated dose of RAL when administered with RIF to HIV and TB co-infected children. P1101 is a phase I/II open-label dose-finding study of RAL with RIF for children 2 to less than 12 years of age beginning treatment for HIV and active TB. Four sites in South Africa. Chewable RAL was given at 12 mg/kg per dose twice daily (twice the usual pediatric dose) with two nucleoside reverse transcriptase inhibitors. Intensive RAL pharmacokinetic sampling was conducted 5 to 8 days after antiretroviral therapy was initiated; a fourth antiretroviral agent was then added. Children were recruited into two age-defined groups: cohort 1 (2 to <6 years old) and cohort 2 (6 to <12 years old). Pharmacological targets [geometric mean (GM) AUC12 h of 14-45 μmol/l h and GM C12 h ≥75 nmol/l) were reached in both cohort 1 (28.8 μmol/l h and 229 nmol/l) and cohort 2 (38.8 μmol/l h and 228 nmol/l). The RAL-based ART was well tolerated by most participants: one participant discontinued treatment because of grade 4 hepatitis that was possibly treatment-related. At week 8, 22 of 24 participants (92%) had HIV RNA concentrations below 400 copies/ml; 19 of 24 (79%) were below 50 copies/ml. Giving 12 mg/kg twice daily of the chewable RAL formulation achieved pharmacokinetic targets safely in HIV-infected children receiving RIF for TB.


Investigations on the antinociceptive activity of crude extracts from Croton cajucara leaves in mice.
The crude leaf extracts of Croton cajucara Benth. were studied for their antinociceptive property in chemical and thermal models of nociception in mice. All the tested extracts (hexanic, chloroformic and methanolic), at oral doses of 100 and 200 mg/kg demonstrated significant inhibition of acetic acid-induced writhing and the second phase response of formalin, but did not manifest a significant effect in hot-plate test.


Roles of the glutathione- and thioredoxin-dependent systems in the Escherichia coli responses to ciprofloxacin and ampicillin.
Recently, it was proposed that some antibiotics stimulate the production of reactive oxygen species (ROS), which contribute to cell death. Later, other research groups have provided arguments against ROS-mediated killing of bacteria by antibiotics. At present, there remain a number of unanswered questions in understanding of the role of ROS in killing by antibiotics. Mutants of Escherichia coli in components of the thioredoxin and glutaredoxin redox pathways used in this study possess a great variability in antioxidant activity, and they therefore are a useful model for the investigation of the role of oxidative stress in bactericidal effect of antibiotics. Statistical analysis did not reveal a significant correlation between the susceptibility of the mutants to ciprofloxacin and ampicillin and their resistance to peroxide stress. However, we found strong reverse correlations between the bactericidal activity of antibiotics and the specific growth rate of these mutants at the moment of drug addition. Supplements changing the level of intra- and extracellular glutathione considerably affected E. coli susceptibility to ciprofloxacin and ampicillin. The effect of GSH precursors on bactericidal activity of antibiotics was also observed in gshA mutants.


Sampling characteristics of the Rotorod, Rotoslide and Andersen machines for atmospheric pollen and spores.
This study shows the superior aeroallergen collecting capabilities of the Rotorod sampler compared to the Rotoslide, Andersen and Durham devices. It collected the largest number and greatest variety of pollen grains and spores. Particle-size distribution was about 150 micron to 2.5 micron. Water wash-off was best prevented by the Rotorod's retracting rod-holders.


Long-term neurodevelopmental outcomes among preterm infants born to mothers with diabetes mellitus.
The long-term effects of maternal diabetes on preterm infant neurodevelopment are unknown. This study aims to determine if there was an increased likelihood of neurodevelopmental impairment in preterm infants born to mothers with diabetes. A retrospective cohort study was conducted on preterm infants with neurodevelopmental evaluations at 18-36 months corrected age using the Bayley Scales of Infant and Toddler Development Third edition. 680 former preterm infants were evaluated. There was no difference in cognitive, language, and motor scores. Infants born to diabetic mothers with AMA were significantly different in cognitive (adjusted-β (a-β),-7.24 [95%CI, -11.719 to -2.769]; P = 0.002) and language domains (a-β,-7.783 [95%CI, -13.603 to -1.963]; (P = 0.009). There was no significant difference in neurodevelopmental outcomes of preterm infants exposed to maternal diabetes. Preterm infants born to mothers with diabetes and AMA demonstrated lower cognitive and language scores at 2 years corrected age.


Phospholipid vesicles increase the survival of freeze-dried human red blood cells.
In a previous report [Z. Török, G. Satpathy, M. Banerjee, R. Bali, E. Little, R. Novaes, H. Van Ly, D. Dwyre, A. Kheirolomoom, F. Tablin, J.H. Crowe, N.M. Tsvetkova, Preservation of trehalose loaded red blood cells by lyophilization, Cell Preservation Technol. 3 (2005) 96-111.], we presented a method for preserving human red blood cells (RBCs) by loading them with trehalose and then freeze-drying. We have now improved that method, based on the discovery that addition of phospholipid vesicles to the lyophilization buffer substantially reduces hemolysis of freeze-dried RBCs after rehydration. The surviving cells synthesize 2,3-DPG, have low levels of methemoglobin, and have preserved morphology. Among the lipid species we studied, unsaturated PCs were found to be most effective in suppressing hemoglobin leakage. RBC-vesicle interactions depend on vesicle size and structure; unilamellar liposomes with average diameter of less than 300 nm were more effective in reducing the hemolysis than multilamellar vesicles. Trehalose loaded RBCs demonstrated high survival and low levels of methemoglobin during 10 weeks of storage at 4 degrees C in the dry state when lyophilized in the presence of liposomes.


Adherence styles of schizophrenia patients identified by a latent class analysis of the Medication Adherence Rating Scale (MARS): a six-month follow-up study.
The purpose of this study was to examine patients' response profiles to the Medication Adherence Rating Scale (MARS) and to evaluate the potential of response styles as predictors of the future course of psychotic disorders in terms of rehospitalisation and maintenance of medication. A total of 371 psychiatric in-patients with schizophrenia or schizoaffective disorder who were taking part in a naturalistic long-term study completed a German version of the MARS. A Latent Class Analysis (LCA) was performed. Five latent classes of response styles could be identified: "moderately adherent", "critical discontinuers", "good compliers", "careless and forgetful", and "compliant sceptics". Class membership was found to be related to the severity of symptoms, level of functioning, insight into illness, insight into necessity of treatment, treatment satisfaction and medication side effects. At a six-month follow-up appointment, significant differences between the classes persisted. Participants showing a "good compliers" response pattern had a significantly better prognosis in terms of rehospitalisation rate and maintenance of the original medication than "critical discontinuers". Evaluation of the MARS by studying response profiles provides informative results that reach beyond the results obtained by an evaluation by scores. Patients can be classified into adherence groups that are of predictive value for long-term patient outcome.


Vitamin D Status and Cancer Incidence, Survival, and Mortality.
Over the last several decades, extensive research on vitamin D and its role on cancer incidence, cancer survival (survival or mortality from cancer among individuals diagnosed with cancer), and cancer mortality (fatal cases occurring during the study period in an initially cancer-free population) has been conducted. A variety of study designs were implemented to explore vitamin D status, assessed by measuring sun exposure, vitamin D intake, and circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although not many randomized controlled trials have examined the relationship between vitamin D and cancer incidence, observational studies have consistently shown a protective association between vitamin D and cancer incidence, especially for colorectal cancer. In addition, randomized controlled trials and most observational studies suggested that vitamin D plays a role in reducing cancer mortality. The potential benefit of vitamin D on cancer mortality may operate during the pre-diagnostic stages by affecting late-stage tumor progression and metastatic seeding, during the treatment phase by complementing or enhancing effects of therapies, or during the post-diagnostic stages. However, further studies are needed to confirm these conclusions, establish the optimal dosage and timing of vitamin D intakes for the most benefit, find which cancer types are affected, and understand the underlying mechanisms.


Cognitive Assessment of Older People: Do Sensory Function and Frailty Matter?
Background: To examine the associations of visual and hearing functions, and frailty with subjective memory complaints (SMCs) in a community primary care pilot project of older people aged 60 years and over. Methods: The study was conducted in 24 community centers. A total of 1949 community-dwelling older people aged between 60⁻97 years were evaluated for which detailed information regarding socio-demographics, lifestyle, and clinical factors were documented at baseline and an average of 12 months later. SMCs were assessed using the 5-item Abbreviated Memory Inventory for the Chinese (AMIC). Visual and hearing functions were measured with two separate single questions. Frailty was assessed using a simple frailty question (FRAIL). Results: At baseline, 1685 (74.6%) participants had reported at least 3 SMCs (AMIC score ≥ 3). Of the 573 participants without / with 1⁻2 SMCs (AMIC score = 0⁻2) at baseline, 75 had incomplete data regarding SMCs and 190 developed at least 3 SMCs after 12 months. After adjustments for age, sex, marital status, educational level, hypertension, and diabetes at baseline, poor vision (OR 2.2 95% CI 1.8⁻2.7), poor hearing (OR 2.2 95% CI 1.8⁻2.8), and frailty (OR 4.6 95% CI 3.1⁻6.7) at baseline were each significantly associated with an increased risk of at least 3 SMCs at follow-up. After a further adjustment for baseline SMCs, the associations remained significant. Similar results were obtained when incident SMCs and improvement in subjective memory were used as the outcome variables; and Conclusions: In the care of older people, detection of sensory impairment and frailty through screening may allow formulation of strategies to prevent or delay the onset of cognitive decline.


Linezolid induced psychosis and hallucination: Case report and literature review.
Various classes of antibiotics have been linked to causing a wide range of neuropsychiatric symptoms. These manifestations range from psychosis and delirium to encephalitis and intracranial hypertension. The prevalence of psychosis adverse drug reactions (ADRs) for individual antibiotics ranges from 0.3 to 3.8%. We report a rare case of linezolid-induced psychosis and hallucination. We report a 52-year-old Asian gentleman who presented with an altered level of consciousness and hallucinations. He was treated for third-degree burns of 31% of the body for two months. Based on clinical and laboratory investigations, linezolid-induced psychosis and hallucination were diagnosed. His Naranjo probability score was +8. The drug was stopped, and the patient recovered successfully. On rare occasions, toxic blood levels of linezolid can lead to neuropsychiatric manifestations. Both linezolid-induced psychosis and hallucinations are manageable by suspension of the drug. Therefore, physicians should monitor the blood levels of this antibiotic to keep their patients safe from such serious adverse effects.


Effects of Dry Needling on Pain in Patients with Knee Osteoarthritis: A Preliminary Study.
Osteoarthritis is one of the most common rheumatological diseases and is also considered as one of the causes of myofascial trigger points (MtrPs). Dry needling (DN) is one of the methods used for the treatment of the MtrPs. The aim of the current study was to investigate the effects of DN on pain in participants with knee osteoarthritis (KOA). In this before and after preliminary clinical trial study, patients with mild to moderate KOA were enrolled. In one session, after determining the location of trigger points in quadriceps and gastrocnemius muscles, the patients underwent DN. The pain was evaluated at baseline, by passing 4 days and 1 month from the intervention using the Visual Analog Scale (VAS). Sixteen patients with a mean age of 56.5 (4.53) years old have completed the study and follow-up period. According to the ANOVA analysis, VAS values indicated a significant decrease in pain score at the 4th and 1 month after the intervention compared to baseline (P < 0.001). There was no significant difference between VAS at the 4th day of intervention and also 1 month later of intervention (P = 0.087). The application of one session DN can lead to improvement in pain intensity in participants with mild to moderate KOA.


The effect for hyperuricemia inpatient of uric acid overproduction type or in combination with topiroxostat on the pharmacokinetics, pharmacodynamics and safety of dotinurad, a selective urate reabsorption inhibitor.
Dotinurad, a novel selective urate reabsorption inhibitor (SURI), increases urinary uric acid excretion. The aim of this study is to examine the pharmacokinetics, pharmacodynamics, and safety of dotinurad according to the type of hyperuricemia, with or without concomitant use of xanthine oxidase inhibitor, in uric acid "overproduction type" patients. This open-label clinical pharmacology study was conducted in a hospital. Dotinurad 1 mg was administered for 7 days to hyperuricemic patients with uric acid "overproduction type" (overproduction group, n = 6; and combination group, n = 6) and uric acid "underexcretion type" (underexcretion group, n = 6). In the combination group, topiroxostat 80 mg was used concomitantly. No significant differences were observed in pharmacokinetics and safety between overproduction group and underexcretion group, and the percent change in serum uric acid level and the amount of urinary uric acid excretion after administration were comparable. In "overproduction type" patients of combination group, the percent change in serum uric acid level significantly increased and the amount of urinary uric acid excretion significantly decreased compared to those of overproduction group. No clinically meaningful differences were observed in safety between the overproduction group and the combination group. In inpatients, differences in hyperuricemic type did not significantly influence the pharmacokinetics, pharmacodynamics, and safety of dotinurad. Moreover, in "overproduction type", the coadministration of dotinurad and topiroxostat had an add-on serum uric acid lowering effect and suppressed urinary uric acid excretion. ClinicalTrials.gov Identifier: NCT02837198.


Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer.
Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P < 0.05, P < 0.0001, and P < 0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P < 0.005 and P < 0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P < 0.0001 and P < 0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM.


Water-Vapor Sorption Processes in Nanoporous MgO-Al2O3 Ceramics: the PAL Spectroscopy Study.
The water-vapor sorption processes in nanoporous MgO-Al2O3 ceramics are studied with positron annihilation lifetime (PAL) spectroscopy employing positron trapping and positronium (Ps)-decaying modes. It is demonstrated that the longest-lived components in the four-term reconstructed PAL spectra with characteristic lifetimes near 2 and 60-70 ns can be, respectively, attributed to ortho-positronium (o-Ps) traps in nanopores with 0.3- and 1.5-1.8-nm radii. The first o-Ps decaying process includes "pick-off" annihilation in the "bubbles" of liquid water, while the second is based on o-Ps interaction with physisorbed water molecules at the walls of the pores. In addition, the water vapor modifies structural defects located at the grain boundaries in a vicinity of pores, this process being accompanied by void fragmentation during water adsorption and agglomeration during water desorption after drying.


Differential effects of cranial radiation on growth hormone response to arginine and insulin infusion.
The growth hormone responses to arginine infusion and to insulin-induced hypoglycemia were studied in 13 patients with neoplastic disease after treatment with radiation and chemotherapy. Patients who received intensive cranial radiation (greater than 2,400 rads) had no response to either arginine or insulin; those who received moderate cranial radiation (greater than or equal to 2,400 rads) had GH response to arginine but not to insulin; patients receiving no cranial radiation responded to both arginine and insulin. These data support the hypothesis that GH secretion in response to arginine infusion has a different mechanism in contrast to the response to insulin-induced hypoglycemia and that the latter is more vulnerable to cranial radiation.


[Changes in thyroid function in primary degenerative dementia processes].
To overcome diagnostic uncertainties in early phases of Alzheimer's disease (pre-senile dementia), the analysis of T-3 and T-4 concentration can be usefully employed. Arising out of the localisation neuropathological findings in Alzheimer type dementia, it could be that hormonal findings perform a useful function as indicators of a change in neurotransmitter activity in this disease.


Integrating Single-cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is the most widely distributed tumor in the world, and its immunotherapy is not practical. Neutrophil is one of a tumor's most abundant immune cell groups. This research aimed to investigate the complex communication network in the immune microenvironment (TIME) of NSCLC tumors to clarify the interaction between immune cells and tumors and establish a prognostic risk model that can predict immune response and prognosis of patients by analyzing the characteristics of Neutrophil differentiation. Integrated Single-cell RNA sequencing (scRNA-seq) data from NSCLC samples and Bulk RNA-seq were used for analysis. Twenty-eight main cell clusters were identified, and their interactions were clarified. Next, four subsets of Neutrophils with different differentiation states were found, closely related to immune regulation and metabolic pathways. Based on the ratio of four housekeeping genes (ACTB, GAPDH, TFRC, TUBB), six Neutrophil differentiation-related genes (NDRGs) prognostic risk models, including MS4A7, CXCR2, CSRNP1, RETN, CD177, and LUCAT1, were constructed by Elastic Net and Multivariate Cox regression, and patients' total survival time and immunotherapy response were successfully predicted and validated in three large cohorts. Finally, the causes of the unfavorable prognosis of NSCLC caused by six prognostic genes were explored, and the small molecular compounds targeted at the anti-tumor effect of prognostic genes were screened. This study clarifies the TIME regulation network in NSCLC and emphasizes the critical role of NDRGs in predicting the prognosis of patients with NSCLC and their potential response to immunotherapy, thus providing a promising therapeutic target for NSCLC.


A comparative study of selenium concentration and glutathione peroxidase activity in normal and breast cancer patients.
The present study was undertaken to compare plasma Se values and glutathione peroxidase (GPX) activity in normal and breast cancer patients. In a case-control study, forty-five breast cancer patients and the same number of healthy women were randomly selected from their population. Se was measured in plasma by atomic absorption spectrophotometry and GPX activity in erythrocytes was measured using a standard spectrophotometric method. Plasma Se concentration in healthy women and breast cancer patients was in the normal range, with no statistically significant difference observed between the two groups (138.40 (sd 40.36) microg/l v. 132.15 (sd 35.37) microg/l, respectively). Erythrocyte GPX activity was significantly (P<0.01) higher in breast cancer patients (24.81 (sd 11.66) U/g Hb) compared with healthy women (20.29 (sd 4.24) U/g Hb). The present study indicated that Se deficiency was not a problem in the participants, and sufficient quantity of this element could increase GPX activity to have a protective effect against oxidative damage.


Leukocyte chemoattractant receptor FPR2 may accelerate atherogenesis.
Atherosclerosis is a chronic inflammatory disease and the number one cause of mortality worldwide. The fundamental causes of atherosclerosis have not been precisely delineated, although pathogenesis clearly involves endothelial dysfunction and both innate and adaptive immunity. Recent evidence suggests that formyl peptide receptor 2 (FPR2), a G protein-coupled receptor (GPCR), mediates a range of inflammatory responses including superoxide production in neutrophils, chemotaxis of monocytes and neutrophils, CCL2 production in endothelial cells (ECs) and monocytes, and increased CXCL8 expression in neutrophils, which are all related with atherogenesis. Therefore, we propose that FPR2 may play a pathogenic role in atherogenesis.


Bioorganosolve pretreatments for simultaneous saccharification and fermentation of beech wood by ethanolysis and white rot fungi.
Ethanol was produced by simultaneous saccharification and fermentation (SSF) from beech wood chips after bioorganosolve pretreatments by ethanolysis and white rot fungi, Ceriporiopsis subvermispora, Dichomitus squalens, Pleurotus ostreatus, and Coriolus versicolor. Beech wood chips were pretreated with the white rot fungi for 2-8 weeks without addition of any nutrients. The wood chips were then subjected to ethanolysis to separate them into pulp and soluble fractions (SFs). From the pulp fraction (PF), ethanol was produced by SSF using Saccharomyces cerevisiae AM12 and a commercial cellulase preparation, Meicelase, from Trichoderma viride. Among the four strains, C. subvermispora gave the highest yield on SSF. The yield of ethanol obtained after pretreatment with C. subvermispora for 8 weeks was 0.294 g g(-1) of ethanolysis pulp (74% of theoretical) and 0.176 g g(-1) of beech wood chips (62% of theoretical). The yield was 1.6 times higher than that obtained without the fungal treatments. The biological pretreatments saved 15% of the electricity needed for the ethanolysis.


The Impact of Reported β-Lactam Allergy on Clinical Outcomes and Antibiotic Use Among Solid Organ Transplant Recipients.
Reported β-lactam allergies (BLAs) are common and frequently inaccurate, but there are limited data on the clinical implications of BLA among solid organ transplant (SOT) recipients. We examined the impact of BLA on clinical outcomes and antibiotic use among SOT recipients. This retrospective cohort study included adult patients undergoing single-organ heart, kidney, liver, lung, or pancreas transplant at a United States academic medical center from 1 April 2017 to 31 December 2020. Demographic and clinical data were collected from the electronic health record. Multivariate median regression was performed to evaluate the association between BLA and days alive and out of the hospital in the first 180 days posttransplant (DAOH180). Multivariate logistic regression was performed to evaluate the association between BLA and antibiotic use. Among 1700 SOT recipients, 285 (16.8%) had a BLA at the time of transplant. BLA was not associated with DAOH180 (adjusted median difference, -0.8 days [95% confidence interval {CI}, -2.7 to 1.2]; P = .43). Patients with BLA were more likely to receive intravenous vancomycin (adjusted odds ratio [aOR], 1.8 [95% CI, 1.3-2.6]; P < .001), clindamycin (aOR, 9.9 [95% CI, 5.1-18.9]; P < .001), aztreonam (aOR, 19.6 [95% CI, 5.9-64.4]; P < .001), fluoroquinolones (aOR, 3.8 [95% CI, 2.8-5.0]; P < .001), or aminoglycosides (aOR, 3.9 [95% CI, 2.5-6.2]; P < .001). BLA was associated with use of β-lactam alternative antibiotics but not DAOH180 among SOT recipients.


[Secondary ambulatory prophylaxis of venous thromboembolism: outcome of patients who were lost to follow-up].
We have attempted to determine the outcome of 87 out-patients who were lost from follow-up. Several factors have been assessed: causes of lost from follow-up duration of oral anticoagulation, recurrent venous thromboembolic events, cause of death (if applicable).


Systematic dose-response of environmental epidemiologic studies: Dose and response pre-analysis.
Meta-analysis approaches can be used to assess the human risks due to exposure to environmental chemicals when there are numerous high-quality epidemiologic studies of priority outcomes in a database. However, methodological issues related to how different studies report effect measures and incorporate exposure into their analyses arise that complicate the pooled analysis of multiple studies. As such, there are "pre-analysis" steps that are often necessary to prepare summary data reported in epidemiologic studies for dose-response analysis. This paper uses epidemiologic studies of arsenic-induced health effects as a case example and addresses the issues surrounding the estimation of mean doses from censored dose- or exposure-intervals reported in the literature (e.g., estimation of mean doses from high exposures that are only reported as an open-ended interval), calculation of a common dose metric for use in a dose-response meta-analysis (one that takes into consideration inter-individual variability), and calculation of response "effective counts" that inherently account for confounders. The methods herein may be generalizable to 1) the analysis of other environmental contaminants with a suitable database of epidemiologic studies, and 2) any meta-analytic approach used to pool information across studies. A second companion paper detailing the use of "pre-analyzed" data in a hierarchical Bayesian dose-response model and techniques for extrapolating risks to target populations follows.


Antioxidant S-allylcysteine prevents gentamicin-induced oxidative stress and renal damage.
Acute renal failure (ARF) is a major complication of gentamicin (GM) treatment, which is effective against gram-negative infections. Since experimental evidence suggests a role of reactive oxygen species (ROS) in GM-induced ARF, in this work we studied the effect of a garlic-derived compound, S-allylcysteine (SAC), which is a free radical scavenger, on GM-induced nephrotoxicity. In rats treated with GM (70 mg/kg/12 h/4 days/s.c.), ARF was evident by the: (i) decrease in creatinine clearance and increase in blood urea nitrogen, (ii) decrease in blood glutathione peroxidase (GPx) activity and increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein, and (iii) necrosis of proximal tubular cells. These alterations were prevented by SAC treatment (250 mg/kg/i.p. 24 h before the first dose of GM and 125 mg/kg/12 h/4 days along GM-treatment). Furthermore, SAC prevented the GM-induced oxidative stress (protein carbonyl groups) and the decrease in manganese superoxide dismutase (Mn-SOD), GPx, and glutathione reductase (GR) activities in renal cortex. In conclusion, SAC ameliorates the GM-induced ARF by a mechanism related, at least in part, to its ability to decrease oxidative stress and to preserve antioxidant enzymes activity in renal cortex.