A novel tissue mechanics-based method for improved motion tracking in quasi-static ultrasound elastography.
Most cancers are associated with biological and structural changes that lead to tissue stiffening. Therefore, imaging tissue stiffness using quasi-static ultrasound elastography (USE) can potentially be effective in cancer diagnosis. USE techniques developed for stiffness image reconstruction use noisy displacement data to obtain the stiffness images. In this study, we propose a technique to substantially improve the accuracy of the displacement data computed through ultrasound tissue motion tracking techniques, especially in the lateral direction. The proposed technique uses mathematical constraints derived from fundamental tissue mechanics principles to regularize displacement and strain fields obtained using Global Ultrasound Elastography (GLUE) and Second-Order Ultrasound Elastography (SOUL) methods. The principles include a novel technique to enforce (1) tissue incompressibility using 3D Boussinesq model and (2) deformation compatibility using the compatibility differential equation. The technique was validated thoroughly using metrics pertaining to Signal-to-Noise-Ratio (SNR), Contrast-to-Noise-Ratio (CNR) and Normalized Cross Correlation (NCC) for four tissue-mimicking phantom models and two clinical breast ultrasound elastography cases. The results show substantial improvement in the displacement and strain images generated using the proposed technique. The tissue-mimicking phantom study results indicate that the proposed method is superior in improving image quality compared to the GLUE and SOUL techniques as it shows an average axial strain SNR and CNR improvement of 44% and 63%, and lateral strain SNR and CNR improvement of 130% and 435%, respectively. The results of the phantom study also indicate higher accuracy of displacement images obtained using the proposed technique, including improvement ranges of 7-84% and 26-140% for axial and lateral displacement images, respectively. For the clinical cases, the results indicate average improvement of 48% and 64% in SNR and CNR, respectively, in the axial strain images, and average improvement of 40% and 41% in SNR and CNR, respectively, in the lateral strain images. The proposed method is very effective in producing improved estimate of tissue displacement and strain images, especially with the lateral displacement and strain where the improvement is highly remarkable. While the method shows promise for clinical applications, further investigation is necessary for rigorous assessment of the method's performance in the clinic.


Clomipramine and benznidazole association for the treatment of acute experimental Trypanosoma cruzi infection.
Alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to improve the efficacy of Chagas disease treatment. This work evaluates the effect of the association of clomipramine (CLO) with benznidazole (BZN) for the treatment of experimental Chagas disease in the acute stage, in Swiss albino mice infected with Trypanosoma cruzi Tulahuen strain. Infected mice were treated with CLO 5mg/kg/day and BZN 50 and 100mg/kg/day, each separately or together. Efficacy of the treatment was evaluated through parasitemia, survival, electrocardiography, histopathological studies, serological and PCR assays at 90 days post-infection (dpi). All treatments significantly (P<0.05) reduced mortality and decreased parasitemia. Histopathological analysis of liver and kidneys of mice treated with CLO and the drug combination showed less injury than mice treated only with BZN. The lower dose of BZN (50mg/kg/day) combined with CLO showed the same efficacy as the habitual dose of BZN (100mg/kg/day) combined with CLO. The therapeutic results from the combination of BZN with CLO presented lesser side effects than the treatment with BZN.


Characterization and quantitation of fatty acids covalently bound to erythrocyte membrane proteins: anion transporter contains 1 mol of fatty acid thiol ester.
Human erythrocyte membranes which had been thoroughly extracted with organic solvents contained 20 nmol of fatty acids/mg dry wt. The major fatty acids were palmitic and stearic with their monoethenoic derivatives as minor constituents. No other fatty acids were detected. When solvent-extracted membranes were digested with Pronase about 90% of the original content of fatty acids was retained in the insoluble residue. Fatty acids were linked to membrane proteins through alkali-labile bonds of which 30% were of a thiol ester and the remainder of an O-ester type. This conclusion is based on differential liberation of fatty acids by hydroxylamine at pH 7.0 and pH 11.0. Two extracts of membranes enriched in peripheral proteins (bands 1, 2, 5 and 2.1, 4.1, 4.2, 6) were prepared and extracted with organic solvents but each contained about six times less fatty acids than the parent solvent-extracted membranes. Glycophorin A contains little if any covalently bound fatty acids. Anion transporter (band 3) contains about 1 mol of thiol ester of fatty acid. This accounts for about half of the thiol ester-linked fatty acids in the parent solvent-extracted membranes. Most of the O-ester-linked fatty acids are linked to an undisclosed membrane protein.


Structural and functional characterisation of the blood cells of the bivalve mollusc, Scrobicularia plana.
Light and electron microscopical studies were carried out in order to characterise the blood cells of the bivalve mollusc, Scrobicularia plana. Three types of haemocytes were recognised: eosinophilic granular haemocytes, basophilic granular haemocytes and basophilic agranular haemocytes. The eosinophilic granulocytes were vesicular and contained large granules whereas the basophilic granulocytes were found to contain small granules and glycogen 'lakes'. The basophilic agranular haemocytes were significantly smaller than the granular haemocytes and had a high nucleus to cytoplasm ratio. Functional characterisation of the blood cells identified activity for the lysosomal enzymes: acid phosphatase, beta-glucuronidase, non-specific esterase and arylsulphatase. There was also a weak staining reaction for phenoloxidase and peroxidase activities. Phagocytosis of Gram-positive bacteria was demonstrated by the haemocytes and antibacterial activity was shown by cell-free haemolymph. Assays to determine release of reactive oxygen species from the haemocytes did not detect any reactive oxygen generation.


Subpial and stellate cells: two populations of interneurons in turtle visual cortex.
Turtle visual cortex has three layers and receives direct input from the dorsolateral geniculate complex of the thalamus. The outer layer 1 contains several populations of interneurons, but their physiological properties have not been characterized. This study used intracellular recording methods followed by filling with Neurobiotin to characterize the morphology and physiology of two populations of layer 1 interneurons. Subpial cells have somata positioned in the outer third of layer 1 and dendrites confined within the band of geniculate afferents that runs from lateral to medial across visual cortex. Their dendrites are composed of a sequence of many beads or varicosities separated by intervaricose segments. They have membrane time constants of tau(o) = 45.5 +/- 5.2 ms and electrotonic lengths of 1.1 +/- 0.2. Subpial cells show spike rate adaptation in response to intracellular current pulses. Stellate cells have somata located in the inner two-thirds of layer 1 and, less frequently, in layers 2 and 3. Their dendrites extend in a stellate configuration across the cortex. They are smooth or sparsely spiny, but never bear distinct varicosities. They have membrane time constants of tau(o) = 155.1 +/- 12 ms and electrotonic lengths of 3.8 +/- 0.5. They show little spike rate adaptation in response to intracellular current pulses. The positions of the two populations of cells in visual cortex and their physiological properties suggest that subpial cells may participate in a feedforward inhibitory pathway to pyramidal cells, whereas stellate cells are involved in feedback inhibition to pyramidal cells.


Yuva spandana - A youth mental health promotion model in India - Design, methods and progress.
A unique youth mental health promotion program called Yuva Spandana is implemented and functional across all districts within Karnataka. Trained guidance providers named Yuva Parivarthakas (YPs) and Yuva Samalochakas (YS) provide support to youth having issues at Yuva Spandana Kendras (YSKs). We highlight the process of development of the program "Yuva Spandana" into a sustainable community-based youth mental health promotion model addressing youth issues across Karnataka and describe the profile of beneficiaries attending YSKs in Karnataka between 2017 and 2019. Yuva Spandana has evolved over time and got established in local-self-governments and communities.


Mechanisms of fatty degeneration in massive rotator cuff tears.
Fatty degeneration of chronically injured muscle is a commonly recognized consequence of massive rotator cuff tears. Current surgical treatments are unable to alter or reverse the progression of fatty degeneration and are associated with poor functional outcomes in these patients. Therefore, a better understanding of the pathophysiology of fatty degeneration is required. As such, recent discoveries in stem cell biology and new animal models have significantly advanced our understanding of the cellular and molecular basis of fatty degeneration. Future studies will facilitate development of novel treatments to prevent the progression of fatty degeneration and improve muscle regeneration in patients with massive rotator cuff tears.


Procalcitonin for Detecting Culture-Positive Sepsis in Neonates: A Prospective, Multicenter Study.
It is unclear if serum procalcitonin (PCT) estimated at sepsis suspicion can help detect culture-positive sepsis in neonates. We evaluated the diagnostic performance of PCT in culture-positive sepsis in neonates. This was a prospective study (February 2016 to September 2020) conducted in four level-3 units in India. We enrolled neonates suspected of sepsis in the first 28 days of life. Neonates with birth weight <750 g, asphyxia, shock, and major malformations were excluded. Blood for PCT assay was drawn along with the blood culture at the time of suspicion of sepsis and before antibiotic initiation. The investigators labeled the neonates as having culture-positive sepsis or "no sepsis" based on the culture reports and clinical course. PCT assay was performed by electrochemiluminescence immunoassay, and the clinicians were masked to the PCT levels while assigning the label of sepsis. Primary outcomes were the sensitivity, specificity, and likelihood ratios to identify culture-positive sepsis. The mean birth weight (SD) and median gestation (IQR) were 2,113 (727) g and 36 (32-38) weeks, respectively. Of the 1,204 neonates with eligible cultures, 155 (12.9%) had culture-positive sepsis. Most (79.4%) were culture-positive within 72 h of birth. The sensitivity, specificity, and positive and negative likelihood ratios at 2 ng/mL PCT threshold were 52.3% (95% confidence interval: 44.1-60.3), 64.5% (60.7-68.1), 1.47 (1.23-1.76), and 0.74 (0.62-0.88), respectively. Adding PCT to assessing neonates with 12.9% pretest probability of sepsis generated posttest probabilities of 18% and 10% for positive and negative test results, respectively. Serum PCT did not reliably identify culture-positive sepsis in neonates.


The role of dydrogesterone in recurrent (habitual) abortion.
The published evidence regarding the administration of dydrogesterone in the treatment of habitual abortion is summarised in this review. Habitual abortion is defined as the loss of three or more consecutive pregnancies without known maternal or foetal pathology. The immunology of early pregnancy seems to determine the rejection or non-rejection of the allogenic embryo. When peripheral mononuclear cells from recurrent aborters are incubated with progesterone or dydrogesterone in vitro, T-helper (Th)2 cytokines such as interleukin (IL)-4 and IL-6 markedly increase whereas the Th1 cytokine interferon-gamma decreases. Additionally, both progesterone and dydrogesterone are thought to inhibit the activity of natural killer cells at the foeto-maternal interface in humans. Progesterone-induced blocking factor (PIBF) mediates the immunological effects of progesterone and dydrogesterone in pregnancy. It affects various phases of the maternal immune response involving both the cellular and humoral immune system, exerts anti-abortive effects and inhibits the release of arachidonic acid. It also favours the production of so-called asymmetric, pregnancy-protecting antibodies. In rodents, blockade of this factor results in the termination of pregnancy and in women considerably lower levels are found in those with threatened abortion or pre-term labour. In order to draw final conclusions as to the usefulness of dydrogesterone in women with a history of recurrent miscarriage, further controlled, blinded, randomised clinical trials are needed.


[Cutaneous leukemia in a horse (author's transl)].
The case of a 16-year-old mare with multiple dermal lymphosarcoma of the histiolymphocytic type is described. Leukaemic changes were not found to be present in the superficial and internal lymph nodes or in the visceral organs.


Sex, glia, and development: interactions in health and disease.
Microglia and astrocytes are the primary immune cells within the central nervous system. Microglia influence processes including neural development, synaptic plasticity and cognition; while their activation and production of immune molecules can induce stereotyped sickness behaviors or pathologies including cognitive dysfunction. Given their role in health and disease, we propose that glia may also be a critical link in understanding the etiology of many neuropsychiatric disorders that present with a strong sex-bias in their symptoms or prevalence. Specifically, males are more likely to be diagnosed with disorders that have distinct developmental origins such as autism or schizophrenia. In contrast, females are more likely to be diagnosed with disorders that present later in life, after the onset of adolescence, such as depression and anxiety disorders. In this review we will summarize the evidence suggesting that sex differences in the colonization and function of glia within the normal developing brain may contribute to distinct windows of vulnerability between males and females. We will also highlight the current gaps in our knowledge as well as the future directions and considerations of research aimed at understanding the link between neuroimmune function and sex differences in mental health disorders.


Assay and characterization of the factor in porcine and bovine plasma which aggregates human platelets.
A sensitive and objective bioassay has been developed to measure the factor present in porcine or bovine plasma which aggregates human blood platelets. The technique is based on direct measurement of platelet aggregation using an electronic particle counter. Using this assay it has been established that platelet aggregating activity is present in both bovine and porcine plasma and in therapeutic concentrates of factor VIII prepared from these materials. Platelet aggregating activity was found to be a function of the factor-VIII-related antigen concentration and independent of factor-VIII coagulant activity. The activity is absent in the plasma from pigs with von Willebrand's disease. It is concluded that factor-VIII-related antigen and the platelet aggregating factor are closely related and may represent one protein species.


Dietary carotenoid pigment supplementation influences hepatic lipid and mucopolysaccharide levels in rainbow trout (Oncorhynchus mykiss).
We assessed the effects of dietary carotenoid pigment supplementation on liver histochemistry in the rainbow trout. One hundred and eight rainbow trout (mean mass 266+/-10 g) were assigned to each of three replicate tanks for each of three dietary treatments; astaxanthin, canthaxanthin, or control at a target dietary inclusion of 100 mg/kg, by top-coating a pigment-free commercially extruded basal diet (Trouw Aquaculture, U.K.). Fish were fed for 3 weeks at a ration of 1.2% body mass/day, in a recirculating freshwater system maintained at 16 degrees C. Frozen liver sections were stained for total lipids, unsaturated lipids, glycogen, mucopolysaccharides, glycogen phosphorylase and aspartate aminotransferase. Relative amounts were measured quantitatively by image analysis. Carotenoid treatment significantly (P<0.05) altered the total lipid profile and hepatic mucopolysaccharide contents of livers of rainbow trout. Results are discussed in relation to the catabolic potential of the liver in carotenoid pigment metabolism.


Modification biological activity of S and R forms of Proteus mirabilis and Burkholderia cepacia lipopolysaccharides by carrageenans.
The modification of biological features of S and R forms of Proteus mirabilis and Burkholderia cepacia LPS by kappa/iota and kappa/beta carrageenans was shown in Limulus activation test, ELISA, human complement activation and apoptotic assay. The role of positively charged substituent Ara4N in lipid A was evaluated as a suspected major domain for interactions with sulphate groups of carrageenans.The experiments obtained by three serological methods indicated that not only lipid A part of LPS but also polysaccharide elements such as core and O-specific chain are involved in interaction with carrageenes. Carrageenans turned out to be non-cytotoxic for A549 cells and were able to inhibit the apoptotic effect caused by lipid A of P. mirabilis and B. cepacia.


Erratum: Alginate/Gelatin Hydrogel Scaffold Containing nCeO2 as a Potential Osteogenic Nanomaterial for Bone Tissue Engineering [Corrigendum].
[This corrects the article DOI: 10.2147/IJN.S388942.].


Development of a rotation phantom for phase contrast MRI sequence validation and quality control.
To develop a reliable, consistent, and reproducible reference phantom for error quantification of phase-contrast MRI so it can be used for validation and quality control. An air-driven rotation phantom consisting of a steadily rotating cylinder surrounded by a static ring both filled with agarose gel was developed. Rotational speed was measured and controlled in real time using an optical counter and a closed-loop controller. Consistency of the phantom was assessed by recording variations in rotational speed. The phantom was imaged with 2D phase-contrast MRI, and the velocity at each point was compared with analytically predicted velocity. Additionally, to examine reproducibility, the phantom was run with the same rotational speed on 2 different days and imaged using the same phase-contrast MRI protocol. The rotation phantom provided consistent rotational speed with 2 revolutions per minute SD from the set value for 20 min. Comparison between predicted and measured velocities demonstrated excellent agreement (intraclass correlation coefficient of 0.99). The RMS error in velocity components were less than 1% of maximum value. The scan-rescan experiment showed that the phantom can reproduce the same velocity distributions (intraclass correlation coefficient of 0.99) using the same rotational speed and MRI settings. The developed rotation phantom provided well-defined and reproducible linear velocity distributions, which can be used for systematic and quantitative error analysis of phase-contrast MRI for a range of known velocities.


Qigong and Musculoskeletal Pain.
Musculoskeletal pain is a widespread symptom that commonly produces considerable disability, particularly in later life. This brief review strove to summarize and critically review the recent research base concerning the use of Qigong as a possible strategy for alleviating longstanding or chronic musculoskeletal pain states. Research reports and literature reviews specifically focusing on Qigong and its impact on various forms of musculoskeletal pain between 2015 and 2019 were sought and analyzed, along with related data. Collectively, these data reveal that while more research is indicated, Qigong practice may help to attenuate pain in varying degrees among adults with different forms of chronic pain with few side-effects. More research is needed to ensure health professionals working with adults who have chronic unrelenting musculoskeletal pain may safely recommend these exercises as one possible remedy for reducing intractable musculoskeletal pain.


Sequential studies of arterial wall regeneration in microporous, compliant, biodegradable small-caliber vascular grafts in rats.
Microporous, compliant, biodegradable vascular grafts prepared from a mixture of polyurethane (95% weight) and poly-L-lactic acid (5% weight) can function as a temporary scaffold for the regeneration of the arterial wall in small-caliber arteries. This study was undertaken to document the sequential events leading to this regeneration. Therefore, polyurethane/poly-L-lactic acid vascular grafts were implanted into the abdominal aorta of rats (N = 28) and were harvested at regular intervals from 1 hour up to 12 weeks after implantation. The implants were evaluated by means of light and electron microscopy. At each time of harvesting, the implants were patent and showed arterial pulsations. No stenosis or dilatation was observed. Endothelial cells grew from the adjacent aortic intima across the anastomoses, from day 6 onward, to form an almost complete neointima after 6 weeks of implantation. Smooth muscle cells also grew from the adjacent aortic media over the graft lattice through the platelet-fibrin coagulum from day 6 onward. The smooth muscle cells, predominantly longitudinally arranged at week 6, but also circularly arranged in some areas at week 12, formed a neomedia in which elastic laminae regenerated. Polymorphonuclear leukocytes and monocytes initially invaded the graft lattices. Fibroblasts, histiocytes, and capillaries grew from the perigraft tissue into the polyurethane/poly-L-lactic acid lattices from day 6 onward, which resulted in the formation of a neoadventitia. The polyurethane/poly-L-lactic acid lattices started to disintegrate from day 12 onward. The regenerative processes in the disintegrating polyurethane/poly-L-lactic acid grafts resulted in the formation of neoarteries, which were of sufficient strength, compliance, and thromboresistance to function as small-caliber arterial substitutes.


Diabetes impairs the enzymatic disposal of 4-hydroxynonenal in rat liver.
This study assesses whether the HNE accumulation we formerly observed in liver microsomes and mitochondria of BB/Wor diabetic rats depends on an increased rate of lipoperoxidation or on impairment of enzymatic removal. There are three main HNE metabolizing enzymes: glutathione-S-transferase (GST), aldehyde dehydrogenase (ALDH), and alcohol dehydrogenase (ADH). In this study we show that GST and ALDH activities are reduced in liver microsomes and mitochondria of diabetic rats; in contrast, ADH activity remains unchanged. The role of each enzyme in HNE removal was evaluated by using enzymatic inhibitors. The roles of both GST and ALDH were markedly reduced in diabetic rats, while ADH-mediated consumption was significantly increased. However, the higher level of lipohydroperoxides in diabetic liver indicated more marked lipoperoxidation. We therefore think that HNE accumulation in diabetic liver may depend on both mechanisms: increased lipoperoxidation and decreased enzymatic removal. We suggest that glycoxidation and/or hyperglycemic pseudohypoxia may be involved in the enzymatic impairment observed. Moreover, since HNE exerts toxic effects on enzymes, HNE accumulation, deficiency of HNE removal, and production of reactive oxygen species can generate vicious circles able to amplify the damage.


Species typical display behavior following stimulation of the reptilian striatum.
Seventy unanesthetized, unrestrained western fence lizards (Sceloporus occidentalis) were electrically stimulated through implanted electrodes. Behavior elicited included the species typical assertion display, elements of the challenge display and elementary locomotor responses: circling, rolling and curling. The assertion and challenge displays were elicited from telencephalic sites whereas the elementary locomotor effects were elicited from electrodes in the brain stem. Assertion displays were consistently elicited in 25 animals at an average threshold current of 46 microA. Sites showing the lowest threshold and greatest reliability were tightly clustered in the striatum and nucleus accumbens. Challenge behavior was elicited in eleven animals at an average threshold of 58 microA. Seven of the animals with challenge responses had electrodes in a small area anterior and dorsal to nucleus sphericus. The implications of these results are discussed relative to current views of the comparative neuroanatomy of the basal ganglia and relative to the basic functional organization of the vertebrate central nervous system.


Sleep disturbances in juvenile myoclonic epilepsy: a sleep questionnaire-based study.
Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect of seizures could have therapeutic implications in terms of sleep disturbances and seizure control. This study aimed to analyze the effect of epilepsy on sleep in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age- and gender-matched controls were recruited into this prospective, hospital-based, case-control study after informed consent and screening for inclusion criteria. They underwent a detailed clinical assessment, electroencephalogram (EEG) and neuroimaging, and were administered validated sleep questionnaires, which included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups had identical numbers of males and females (M: F=22: 28), without any significant difference in the age and body mass index (BMI). The clinical profile of JME was similar to published literature while the prevalence of EEG abnormalities was less compared to similar studies. The mean ESS and PSQI scores and the number of subjects with abnormal scores on one or both questionnaires were significantly more in patients. Patients had a higher prevalence of sleep disturbances, insomnia and excessive daytime somnolence. No significant seizure- or treatment-related factors influencing sleep could be identified. This study, the first of its kind, revealed that patients with JME have significant sleep disturbances characterized by excessive daytime sleepiness and disturbed night sleep, despite adequate medications and good seizure control. The role of VPA in the genesis of these symptoms needs clarification.


Surface-Enhanced Raman Scattering of Silicon Nanocrystals in a Silica Film.
Surface-enhanced Raman scattering (SERS) is an intriguing effect, efficiency of which depends on many factors and whose applicability to a given system is not obvious before the experiment. The motivation of the present work is to demonstrate the SERS effect on silicon nanocrystals (Si-nc) embedded in silica, the material of high technological importance. Using the Ag overlayer method, we have found the SERS effect for this material. The best result is obtained for Ag layers of a weight thickness of 12 nm, whose surface plasmons are in a resonance with the laser wavelength (488 nm). The enhancement obtained for the Raman signal from 3-4-nm Si-nc in a 40-nm SiOx film is above 100. The SERS effect is about twice stronger for ultra-small Si-nc (~1 nm) and/or disordered silicon compared to Si-nc with sizes of 3-4 nm. The SERS measurements with an Ag overlayer allow detecting silicon crystallization for ultra-thin SiOx films and/or for very low Si excess and suppress the Raman signal from the substrate and the photoluminescence of the film.


Small leucine rich proteoglycans, a novel link to osteoclastogenesis.
Biglycan (Bgn) and Fibromodulin (Fmod) are subtypes of the small leucine-rich family of proteoglycans (SLRP). In this study we examined the skeletal phenotype of BgnFmod double knockout (BgnFmod KO) mice and found they were smaller in size and have markedly reduced bone mass compared to WT. The low bone mass (LBM) phenotype is the result of both the osteoblasts and osteoclasts from BgnFmod KO mice having higher differentiation potential and being more active compared to WT mice. Using multiple approaches, we showed that both Bgn and Fmod directly bind TNFα as well as RANKL in a dose dependent manner and that despite expressing higher levels of both TNFα and RANKL, BgnFmod KO derived osteoblasts cannot retain these cytokines in the vicinity of the cells, which leads to elevated TNFα and RANKL signaling and enhanced osteoclastogenesis. Furthermore, adding either Bgn or Fmod to osteoclast precursor cultures significantly attenuated the cells ability to form TRAP positive, multinucleated giant cells. In summary, our data indicates that Bgn and Fmod expressed by the bone forming cells, are novel coupling ECM components that control bone mass through sequestration of TNFα and/or RANKL, thereby adjusting their bioavailability in order to regulate osteoclastogenesis.


[Recommendations for editing pathology reports of colorectal cancer].
The purpose of these recommendations is to provide an informative report for the clinician. The recommendations have been divided into two major areas 1) a standardized form, 2) items that provide an informative gross description and diagnostic features that are recommended to be included in every report. In special circumstances, the recommendations may not be applicable.


Comparison of anterior mandibular alveolar thickness and height in young adults with different sagittal and vertical skeletal relationships: A CBCT Study.
Alveolar bone surrounding mandibular incisors dictates the range of buccolingual inclination that can be achieved with treatment. The objective of this study was to evaluate the mandibular anterior alveolar thickness and height in individuals with different sagittal and vertical skeletal relationships. Cone beam computed tomography scans of 53 individuals (22 males and 31 females; mean age 21.19±3.7 years) were classified into 3 groups according to the sagittal skeletal relationship (class I, class II, and class III) and the vertical growth pattern (hyperdivergent, normodivergent, and hypodivergent). The alveolar thickness and height of both mandibular central incisors were measured. Group comparisons were performed with analysis of variance and post hoc Scheffé tests. Multiple linear regression was applied to evaluate the influence of all variables on the alveolar conditions. Alveolar thickness and height showed no significant differences among the class I, II and III groups (6 and 7mm regardless of the sagittal group, P>0.05). The middle and lower alveolar thicknesses were significantly smaller in hyperdivergent (5.76mm and 6.34mm) and normodivergent (6.29mm and 7.40mm) than hypodivergent individuals (6.63mm and 8.27mm respectively). The lingual alveolar height was smaller in hyperdivergent (6.04mm) than hypodivergent individuals (7.93mm) (P=0.029, 95%CI: 0.15-3.63) and the lingual bone height was smaller in hypodivergent (3.24mm) than hyperdivergent individuals (5.06mm) (P=0.029, 95%CI: 0.15-3.48). Multiple linear regression indicated a significant influence of the root length on the alveolar thickness and height. The sagittal skeletal relationship showed no influence on the alveolar thickness or height, even if dental compensation was present. Hyperdivergent individuals showed smaller alveolar thicknesses and heights than hypodivergent individuals.


The natural history of a family of transplantable melanomas in hamsters.
We have characterized a family of transplantable melanomas in Syrian (golden) hamsters, which originated in 1959 as a spontaneous melanoma of hamster skin, and which has been maintained since then by serial passage. Emphasis has been placed on using the same method of transplantation, keeping strict records on all passages, and applying the same investigative techniques, in order to trace tumor behavior over long periods of time. This tumor family consists of five variants linked by common origin, but which differ with respect to differentiation level, malignancy, intermediary metabolism, chromosome number, and cell surface properties. Once established, these melanomas possessed a considerable degree of phenotypic stability over decades of passaging. One tumor line in this family is emphasized. The Ab amelanotic melanoma lost its differentiated functions (the ability to synthetize melanin) a quarter of a century ago, and since then has remained dedifferentiated in serial passage in hamsters. After transfer to primary cell culture, the Ab melanoma cells differentiate readily and lose much of their proliferative potential. This process is reversible by reimplantation of the cells into a hamster. Inasmuch as this hamster melanoma system meets many of the conditions required for an experimental tumor model, five melanoma variants are characterized concisely and compared to other melanomas in humans and animals. Mechanisms by which new melanoma variants arise are discussed and compared to some phenomena in the evolution of the species.


Arteriolar diameter and spontaneous vasomotion: importance of potassium channels and nitric oxide.
Arterioles display cyclic variations in diameter, termed vasomotion initiated by smooth muscle cells (SMCs), but the endothelium should also be evaluated due to its modulatory role on vessel tone. Since nitric oxide (NO) and prostacyclin (PGI2) regulate SMC tone and activate K(+) currents, we have investigated their role on vasomotion, by observing effects of topical application of N(ω)-nitro-l-arginine (L-NA, NO synthesis inhibitor), glibenclamide (KATP channel inhibitor), sodium nitroprusside (SNP, NO donor), iloprost (PGI2 analogue) and methylene blue (MB, cGMP production inhibitor) on the cheek pouch preparation of anesthetized male hamsters. L-NA (10(-10)-10(-6)M) induced vasoconstriction, reduction and abolition of vasomotion. MB (10(-7) to 10(-5)M) reduced mean arteriolar diameter with no changes on vasomotion. In the presence of 10(-6)M of MB, addition of 10(-6)L-NA totally abolished vasomotion without further constriction. Glibenclamide (10(-6)M) in the presence of L-NA at equimolar concentration restored both vasomotion frequency and amplitude. This effect was not observed in the presence of TEA 5mM. SNP (10(-10)-10(-6)M) induced a dose-dependent increase of arteriolar diameter and decreased vasomotion. Iloprost (10(-12)-10(-6)M) induced a concentration dependent increase of arteriolar diameter, reduced vasomotion frequency, but in lower concentrations (10(-12)-10(-10)M) increased its amplitude and in higher concentrations (10(-9)-10(-6)M) decreased it. SNP and iloprost inhibited vasomotion at 10(-7)M; however, at this concentration SNP and iloprost induced an increment of 35% and 50% of the initial arteriolar diameter, respectively. In the presence of L-NA (10(-6)M), vasomotion was restored by SNP at 10(-10)M and iloprost 10(-12)M, which corresponded to 80% of the initial diameter value. Around the initial (control) arteriolar diameter value, vasomotion presented its highest frequencies and amplitudes. Cessation of vasomotion occurred with L-NA (10(-6)M) in the presence of SNP (10(-6)M) and iloprost (10(-7)M) when arteriolar diameter reached 150% and 120% of its initial value, respectively. In conclusion, the present study strongly suggests that vasomotion (1) is not solely related to vascular tone, (2) needs an interplay between vascular tone and membrane currents and (3) could be modulated by NO (but not cGMP) and KATP channels. In addition, our results point to the existence of dissociation between vasomotion frequency and amplitude.


Clinical evaluation of a new serum tumour marker CA 242 in pancreatic carcinoma.
The aim of this study was to evaluate the new monoclonal tumour marker CA 242 in the diagnosis of pancreatic carcinoma and to compare it with the established markers CA 50 and CEA. Serum concentrations were determined in 113 patients with jaundice, in 20 patients with laboratory values suggesting cholestasis, and in 60 patients with a suspicion to have chronic pancreatitis. Twenty-four of these 193 patients had pancreatic carcinoma and two patients had carcinoma of papilla of Vater. The sensitivities of CA 242, CA 50 and CEA were 80.7%, 96.1%, and 92.3%, respectively. The specificities were 79.0%, 58.0%, and 59.2%. The sensitivities of combinations of CA 50 and CEA with CA 242 did not exceed the sensitivity of CA 50 alone. The specificity of CA 242 was improved by combining it with CEA (92.2%). The serum marker CA 242 seems to be less sensitive than CEA and CA 50 in the detection of pancreatic carcinoma, but it may prove useful because of its high specificity.


Two syngeneic cell lines from human breast tissue: the aneuploid mammary epithelial (Hs578T) and the diploid myoepithelial (Hs578Bst) cell lines.
We characterized two human cell lines (Hs578T and Hs578Bst), which provide several unique features that should be useful in the study of breast disease. Hs578T, derived from a carcinosarcoma, is epithelial in origin. Hs578Bst, established from normal tissue peripheral to the tumor, is myoepithelial in origin. This is the first report of companion cell lines, one malignant and one normal, established from the same organ.


The influence of kidney transplantation on carnitine metabolism.
In this study, we examined all three plasma carnitine fractions, free carnitine (FC), short-chain acyl- (SCC), and long-chain acylcarnitine (LCC), as well as the urinary excretion of FC and SCC in 62 patients with functioning renal allografts 1-70 months following the kidney transplantation (KT). Patients were classified into three groups according to their transplant function, as characterized by the serum creatinine concentration (CR). A comparison with normal subjects (n = 20) and with patients on chronic hemodialysis (HD, n = 46) revealed a complete normalization of all carnitine plasma fractions for group I patients (Cr less than 120 mumol/l). In contrast, significant elevations of plasma free and esterified carnitine were found in group II (Cr greater than 120, less than 200 mumol/l; with FC + 27%, SCC + 82%, and LCC + 49% and group III patients (Cr greater than 200 mumol/l; with FC + 39%, SCC + 122%, and LCC + 106%), as compared to healthy subjects (p less than 0.001). The elevations in concentrations of SCC were more pronounced than those of FC; consequently, we found a higher ratio of acylcarnitine (AC) to FC in group III than in group I patients (+ 41%, p less than 0.001). Yet even in the former group, this ratio was found to be markedly reduced when compared to HD patients (-41%, p less than 0.001). We found no significant differences in the urinary excretion of FC and SCC between the 3 groups of KT patients. It is thus to conclude that in patients with a well-functioning transplant, the pattern of carnitine fractions in plasma is fully normalized. The decrease in the ratio of AC to FC following a successful KT might suggest a better availability of FC and thereby be associated with an enhanced fatty acid oxidation.


[On Dwyer's scoliosis operation using memory alloy wire (author's transl)].
In Dwyer's spinal column correction a titanium cable is stretched from vertebra to vertebra by a special clamp and secured to each vertebra with screws and clips. It is suggested to replace the titanium wire with wire consisting of the memory alloy NiTi. This will permit the prestretched wire to be tensioned by heating it to 60 deg C after it has been fixed at its ends in the vertebrae. The functional principle of the NiTi memory wire was demonstrated in an experiment carried out on a plastic model. This consists of 8 plastic vertebrae with 30 mm sides which are connected by interposed wedge-shaped soft rubber discs, giving the model a curved shape. Memory wire prestretched by 7% is led through eylets on the convex side and fixed at the ends. On being heated (electrically in this experiment for the sake of simplicity), the wire shortens, righting the model so that it assumes a straight shape. The authors also describe in detail the manufacture of the alloy, i.e. the melting and shaping operations, as well as the properties of the material, that is, the stress-strain and strain-temperature relationships and the transformation temperatures, as well as mechanical problems.


Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease.
The Hippo (MST1/2) pathway plays a critical role in restricting tissue growth in adults and modulating cell proliferation, differentiation, and migration in developing organs. Netrin1, a secreted laminin-related protein, is essential for nervous system development. However, the mechanisms underlying MST1 regulation by the extrinsic signals remain unclear. Here, we demonstrate that Netrin1 reduction in Parkinson's disease (PD) activates MST1, which selectively binds and phosphorylates netrin receptor UNC5B on T428 residue, promoting its apoptotic activation and dopaminergic neuronal loss. Netrin1 deprivation stimulates MST1 activation and interaction with UNC5B, diminishing YAP levels and escalating cell deaths. Knockout of UNC5B abolishes netrin depletion-induced dopaminergic loss, whereas blockade of MST1 phosphorylating UNC5B suppresses neuronal apoptosis. Remarkably, Netrin1 is reduced in PD patient brains, associated with MST1 activation and UNC5B T428 phosphorylation, which is accompanied by YAP reduction and apoptotic activation. Hence, Netrin1 regulates Hippo (MST1) pathway in dopaminergic neuronal loss in PD via UNC5B receptor.


Predicting portal venous anomalies by left-sided gallbladder or right-sided ligamentum teres hepatis: A large scale, propensity score-matched study.
Right-sided ligamentum teres (RSLT) is often associated with portal venous anomalies (PVA) and is regarded as a concerning feature for hepatobiliary intervention. Most studies consider RSLT to be one of the causes of left-sided gallbladder (LGB), leading to the hypothesis that LGB must always be present with RSLT. However, some cases have shown that right-sided gallbladder (RGB) can also be present in livers with RSLT. To highlight the rare variation that RSLT may not come with LGB and to determine whether ligamentum teres (LT) or gallbladder location is reliable to predict PVA. This study retrospectively assessed 8552 contrast-enhanced abdominal computed tomography examinations from 2018 to 2021 [4483 men, 4069 women; mean age, 59.5 ± 16.2 (SD) years]. We defined the surrogate outcome as major PVAs. The cases were divided into 4 subgroups according to gallbladder and LT locations. On one hand, we analyzed PVA prevalence by LT locations using gallbladder location as a controlled variable (n = 36). On the other hand, we controlled LT location and computed PVA prevalence by gallbladder locations (n = 34). Finally, we investigated LT location as an independent factor of PVA by using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). We found 9 cases of RSLT present with RGB. Among the LGB cases, RSLT is associated with significantly higher PVA prevalence than typical LT [80.0% vs 18.2%, P = 0.001; OR = 18, 95% confidence interval (CI): 2.92-110.96]. When RSLT is present, we found no statistically significant difference in PVA prevalence for RGB and LGB cases (88.9 % vs 80.0%, P > 0.99). Both PSM and IPTW yielded balanced cohorts in demographics and gallbladder locations. The RSLT group had a significantly higher PVA prevalence after adjusted by PSM (77.3% vs 4.5%, P < 0.001; OR = 16.27, 95%CI: 2.25-117.53) and IPTW (82.5% vs 4.7%, P < 0.001). RSLT doesn't consistently coexist with LGB. RSLT can predict PVA independently while the gallbladder location does not serve as a sufficient predictor.


Duration of involuntary infertility and subsequent pregnancy.
During 1978-1983, 1,040 couples had been evaluated at our infertility clinic and subsequently followed up for an average of two years. The length of time the couple had been trying for a pregnancy (trying time) is shown to be strongly related to the subsequent chances of pregnancy. There are few effective treatments for male infertility and, therefore, these data may represent the spontaneous fertility rates from an untreated population. This background pregnancy rate should be useful to any physician planning a trial of treatment for the infertile couple when pregnancy is the success criterion, and allowance needs to be made for this spontaneous pregnancy rate when analyzing the results of treatments. Review of the literature suggests that some reported results could be misleading because of failure to allow for this background pregnancy rate.


Studies on the occurrence of ophthalmopathy in Graves' disease.
Eye disease was associated with hyperthyroidism in 202 of 221 patients with active Graves' ophthalmopathy (91.4%) and was not accompanied by thyroid hyperfunction (euthyroid Graves' disease) in the remaining 19 (8.6%). All the latter patients had some mild thyroid abnormalities (thyroid autoantibodies, negative TRH test, negative T3 suppression test, goitre). Sex distribution analysis evidenced a higher prevalence in females with a female/male ratio of 2.1 which was, however, significantly lower (P less than 0.05) than that observed in control (Graves' disease patients without overt ophthalmopathy (female/male ratio = 3.4]. Patients with euthyroid Graves' disease showed a female/male ratio of 0.7. Age distribution revealed a peak prevalence in the 5th decade of life, identical to that of Graves' disease without ophthalmopathy. A close temporal relationship between the onset of hyperthyroidism and the onset of ophthalmopathy was found, since in about 85% of the patients the first ocular manifestations occurred within +/-18 months around the onset of hyperthyroidism.


Targeting atypical trypanosomatid DNA topoisomerase I.
Tropical diseases produced by kinetoplastid protozoa are among humanity's costliest banes, owing to high mortality and the economic burden resulting from morbidity. Drug resistant strains of parasites, together with insecticide-resistant vectors, are contributing to their increased prevalence in the developing world. Their extension now threatens industrialized countries because of opportunistic infections in immuno-compromised individuals. Current chemotherapy is expensive, has undesirable side effects and, in many patients, is only marginally effective. Based on the clinical success of camptothecin derivatives as anticancer agents, DNA topoisomerases have been identified as targets for drug development. The substantial differences in homology between trypanosome and leishmania DNA topoisomerase IB compared with the human form provides a new lead in the study of the structural determinants that can be targeted.


Following molecular transitions with single residue spatial and millisecond time resolution.
"Footprinting" describes assays in which ligand binding or structure formation protects polymers such as nucleic acids and proteins from either cleavage or modification; footprinting allows the accessibility of individual residues to be mapped in solution. Equilibrium and time-dependent footprinting links site-specific structural information with thermodynamic and kinetic transitions, respectively. The hydroxyl radical (*OH) is a uniquely insightful footprinting probe by virtue of it being among the most reactive chemical oxidants; it reports the solvent accessibility of reactive sites on macromolecules with as fine as a single residue resolution. A novel method of millisecond time-resolved *OH footprinting is presented based on the Fenton reaction, Fe(II) + H(2)O(2) --> Fe(III) + *OH + OH(-). It is implemented using a standard three-syringe quench-flow mixer. The utility of this method is demonstrated by its application to the studies on RNA folding. Its applicability to a broad range of biological questions involving the function of DNA, RNA, and proteins is discussed.


[Impact of adverse events on the practices of 15 general practitioners].
General practitioners are sometimes faced with adverse events, which we define here as "all untoward or unfortunate events occurring unintentionally during the provision of health care services, but also all such events related to any kind of intervention during care." While their social, economic, and health repercussions are often studied, little is known about their effects on general practitioners, except perhaps for their legal consequences. Our principal objectives here were to study the impact of adverse events (including medical errors) on the practices of general practitioners and to study their representations of the concepts of adverse events and medical errors. This qualitative work is based on interviews with 15 general practitioners in the Rhone-Alpes region. This study collected 66 real situations experienced and identified as adverse events by the subjects. Analysis shows that these events had a major impact on these practitioners: they caused changes in their procedures for diagnosis and treatment, had sometimes important psychological consequences, induced them to participate in targeted continuing education, and increased their awareness of the legal aspects of some practices, including, for example, record-keeping. Most expressed a need to discuss these situations, especially in peer groups. It appears essential to study adverse events and professional practices in primary care and to facilitate their ongoing study, especially in the area of family care.


Systematic review and metaanalysis of perinatal outcomes after radiofrequency ablation and bipolar cord occlusion in monochorionic pregnancies.
The aim of this study was to analyze perinatal outcomes after selective reduction in monochorionic pregnancies with the use of either radiofrequency ablation (RFA) or bipolar cord occlusion (BCO). This was a systematic review and metaanalysis that included all studies with ≥5 cases that described perinatal outcomes after BCO or RFA that were identified in PubMed, Embase, Web of Science, COCHRANE, CINAHL, Academic Search Premier, Science Direct, and MEDLINE that were published between 1965 and July 2014. For count data, incidence risk ratios (IRR; 95% confidence interval [CI]) were calculated with BCO as the reference standard. The analysis included 481 cases of BCO and 320 cases of RFA from 17 studies. The mean median gestations at procedure were 21.1 ± 1.2 weeks (BCO) and 18.8 ± 2.5 weeks (RFA; P = .03). The rate of cotwin death was higher in the RFA group (14.7%) vs the BCO group (10.6%; IRR, 1.38; 95% CI, 0.93-2.05; P = .11). The live birth rate was 81.3% for the RFA group and 86.7% in the BCO group (IRR, 0.93; 95% CI, 0.80-1.09; P = .41). BCO had higher neonatal death rates (8.1%) vs RFA (4.5%; IRR, 0.56; 95% CI, 0.30-1.04; P = .07). Overall survival was 76.8% for RFA and 79.1% for BCO (IRR, 0.97; 95% CI, 0.82-1.14; P = .72); however, none of these differences were statistically significant. Preterm premature rupture of membranes occurred in 17.7% of RFA cases and 28.2% of the BCO cases (IRR, 0.63; 95% CI, 0.43-0.91; P = .01). The mean median gestational age at delivery was 34.7 ± 1.7 weeks in the RFA group and 35.1 ± 1.6 weeks in the BCO group. Our data do not demonstrate clearly the superiority of 1 procedure over the other. The clinical situation and preference of the operator are important considerations. Rates of preterm delivery and preterm premature rupture of membranes remain substantial for both procedures.


Language: Do Bilinguals Think Differently in Each Language?
Whether the representation of concepts depends on the language used to express them is controversial. A new study with sign-speech bilingual participants has found that neural representations of semantic categories, such as fruit, are shared across languages but individual items, such as apple, are not.


Mobilizing and Delivering Essential Meals to Children and Families Affected by School Closures During COVID-19 and Beyond.
The closure of schools in response to COVID-19 compromised access to essential meals for many students. The Emergency Meals-to-You program, a public/private partnership, was set up to address this challenge. More than 38.7 million meals were delivered between April and August 2020. This study explores lessons learned and identifies strategies for strengthening food access and security at schools and beyond. Qualitative research methods were used. This included interviews and focus groups with participants involved in setting up and delivering the Emergency Meals-to-You program. Data were thematically analyzed using key phrases, ideas, and concepts, and interpreted. The program leveraged a multisectoral approach. Components relied on each other and included: schools, public/private partnership, eligibility, relationships, experience, centralized communication, food quality and branding, logistics, and transport. Strategies identified to strengthen food access focused on integration with emergency management structures, understanding food needs at the school level, building a fully procurable menu, and allowing distribution to be rapidly scaled. The lessons identified and strategies recommended provide a framework for working across the emergency management spectrum (school to national level) to strengthen food access and availability for students and their families affected by a pandemic, disaster, or crisis situation.


Contributions of Respiration and Heartbeat to the Pulmonary Blood Flow in the Fontan Circulation.
In the Fontan circulation, driving forces with respiration, heartbeat, and lower limb muscle pump are relevant. However, the mechanics of these forces has not been proven, and their effects on the Fontan circulation remain unclear. We performed catheter examinations and measured pressure and flow velocity simultaneously in the bilateral pulmonary arteries of 12 Fontan patients 1 year after the operation. The pulmonary pressure and flow velocity data were decomposed into respiratory and heartbeat components by discrete Fourier analysis. We then calculated respiratory and cardiac wave intensity (WI) based on the respiratory and heartbeat components of pressure and flow velocity data. Respiratory WI formed 2 negative peaks, a backward expansion wave during the inspiratory phase, and then a backward compression wave during the expiratory phase. In 2 phrenic nerve palsy cases and 1 case of a patient on a respirator, respiratory WI showed disturbed patterns and a negative pattern, respectively. Cardiac WI showed 2 or 4 negative peaks, the time phase of which matched that of the atrial contractions. WI analysis elucidated that inspiration acts as a sucking driving force and increases the pulmonary blood flow in the Fontan circulation. Respiratory complications compromise efficiency in the Fontan circulation. It was also revealed that the pulmonary blood flow was mutually dammed up and sucked in by increases and decreases in atrial pressure.


Living with chronic illness: a phenomenological study of the health effects of the patient-provider relationship.
To understand the patient-healthcare provider (HCP) relationship from the lived experience of women with chronic disease and determine how this relationship affects women's health. Narrative accounts of 25 women's relationships with HCPs in repeated group and individual interviews were audio-taped and transcribed verbatim. Interpretive phenomenology was used to explore the data using three interconnected modes of paradigm cases, exemplars, and themes. Women with chronic disease believed their health was significantly affected by their relationships with HCPs. They experienced a greater sense of well-being and security in connected relationships and had more confidence and motivation to manage their illness. This research suggests that for women with chronic disease, relationships with HCPs that are connected, and characterized by partnership, and personableness result in the women feeling better in many dimensions. The context of today's healthcare system often pushes the nurse practitioner (NP) to provide care more attuned to medical issues, leaving little time for the development of connected relationships. In spite of this pressure, NPs need to strive to develop relationships with patients that are intersubjective/connected.


The predictive value of neuroendocrine markers and p53 for response to chemotherapy and survival in patients with advanced non-small cell lung cancer.
A minority of patients (30-40%) with advanced non-small cell lung cancer (NSCLC) have objective responses to chemotherapy. Therefore, defining molecular features that determine resistance or response to chemotherapy would have important implications in this disease. Several studies have suggested that patients whose tumors have neuroendocrine features may be more responsive to chemotherapy. In addition, increased expression of p53 may play a role in chemotherapy resistance in patients with NSCLC. The objective of this study was to analyze retrospectively, the correlation between marker expression and response to chemotherapy and survival using immunohistochemistry for neuroendocrine markers and p53. Ninety patients with unresectable stage III or IV NSCLC, treated with platinum based combination chemotherapy were evaluated. The pathological specimens were obtained prior to chemotherapy. There was no statistically significant correlation between any individual marker and response to chemotherapy. However, patients with tumors with increased expression of p53 were more likely to have progressive disease following chemotherapy (P=0.02). Similarly, patients with tumors lacking neuroendocrine expression and with increased expression of p53 were more likely to have progressive disease when compared to patients with tumors with normal p53 expression and neuroendocrine differentiation (P=0.03). Normal expression of p53 along with the presence of neuroendocrine differentiation was a favorable factor for both survival (P=0.05) and time to disease progression (P=0.04) in the multivariate analysis. The presence of neuroendocrine markers alone was not predictive of response to chemotherapy and did not impact on the survival of this group of patients with advanced stage NSCLC. The normal expression of p53 together with neuroendocrine differentiation seems to impact favorably on overall survival time and time to disease progression without significant improvement in response to chemotherapy.


Long-term effects of chronic depressive symptoms among low-income childrearing mothers.
Longitudinal studies of maternal depression in the postpartum period have demonstrated that a chronic state of depressive symptoms is not rare. In spite of this, however, the characteristics of chronically depressed mothers have rarely been studied. This study examines the demographic and socioenvironmental characteristics across time of childrearing women with chronic depressive symptoms. A cohort of 476 childrearing lower-income mothers was interviewed from the first trimester of pregnancy through the tenth year postpartum. The Center for Epidemiologic Studies-Depression Scale (CES-D; Radloff, L. (1977) Appl Psychol Meas 1:385-401) was used to define depressive symptomatology. Four groups were defined based on the CES-D scores at 18 months, 3, 6 and 10 years: never-depressed (CES-D < 16), depressed only at one phase (CES-D > or = 16), chronically mildly depressed (CES-D > 16 and < or =24 at three or more phases), and chronically severely depressed (CES-D > or = 25 at three or more times). Demographic and socioenvironmental characteristics of the groups were evaluated across time. Chronically depressed women compared to never-depressed women were less likely to be married, had less education, had lower family income, and were more likely to use substances. They reported more frequent arguments with close family members or friends, separation/divorce with partners, financial problems, less social support, and more financial strain. Women who continue to be depressed across the 10 postpartum years have less optimal outcomes compared to women who are not depressed and those who are only intermittently depressed. Pregnancy and delivery and subsequent pediatric visits are important times to identify women who are depressed.


Efficacy of two topical combinations containing emodepside plus praziquantel, and emodepside plus praziquantel plus tigolaner, for the treatment of troglostrongylosis in experimentally infected cats.
Feline troglostrongylosis caused by Troglostrongylus brevior is increasingly reported in European countries. Although the disease can be severe and potentially life-threatening, especially in kittens and young cats, effective treatment options are still limited. Two administrations of emodepside 2 weeks apart have shown promising results for the treatment of T. brevior infection in single cases and in a field trial. Therefore, the present study has been conducted to evaluate the efficacy of two spot-on combinations containing emodepside (i.e. 2.14% w/v emodepside and 8.58% w/v praziquantel - Profender®, and 2.04% w/v emodepside, 8.14% w/v praziquantel and 9.79% w/v tigolaner - Felpreva®) in the treatment of troglostrongylosis under experimental conditions. Twenty-four cats were experimentally infected with T. brevior and randomly assigned to one of three groups of eight cats each, i.e. (i) Group 1 (G1) left untreated, (ii) Group 2 (G2) receiving Profender® on Days 28 and 44, and (iii) Group 3 (G3) receiving Felpreva® on Day 28 and Profender® on Day 44. Doses corresponded to the minimum effective dose of 0.140 and 0.148 ml/kg body weight, for Profender® and Felpreva®, respectively. The primary efficacy criterion was the number of viable adult T. brevior counted at necropsy conducted between Days 69 and 72. The fecal shedding of first-stage larvae (L1) was also assessed. L1 of T. brevior were detected in samples from all cats within 20 days post-infection. At necropsy, 4 of 8 G1 cats harbored adult T. brevior, while no adult T. brevior worms or other development stages were recovered from any of the G2 and G3 cats. The primary efficacy criterion was not evaluated as the worm counts in G1 did not meet VICH guideline requirements. After the first treatment (Day 28), most G2 and G3 cats were negative at the Baermann examination. After the second treatment (Day 44), L1 were found in two cats from G2 on Day 49 and in one G3 cat on Day 51. No adverse events occurred in G2 and G3 cats. These results indicate that two applications of emodepside spot-on given 2 weeks apart represent a safe and efficacious treatment regime against troglostrongylosis.


Genome-wide association mapping of ethanol sensitivity in the Diversity Outbred mouse population.
A strong predictor for the development of alcohol use disorder (AUD) is altered sensitivity to the intoxicating effects of alcohol. Individual differences in the initial sensitivity to alcohol are controlled in part by genetic factors. Mice offer a powerful tool to elucidate the genetic basis of behavioral and physiological traits relevant to AUD, but conventional experimental crosses have only been able to identify large chromosomal regions rather than specific genes. Genetically diverse, highly recombinant mouse populations make it possible to observe a wider range of phenotypic variation, offer greater mapping precision, and thus increase the potential for efficient gene identification. We have taken advantage of the Diversity Outbred (DO) mouse population to identify and precisely map quantitative trait loci (QTL) associated with ethanol sensitivity. We phenotyped 798 male J:DO mice for three measures of ethanol sensitivity: ataxia, hypothermia, and loss of the righting response. We used high-density MegaMUGA and GigaMUGA to obtain genotypes ranging from 77,808 to 143,259 SNPs. We also performed RNA sequencing in striatum to map expression QTLs and identify gene expression-trait correlations. We then applied a systems genetic strategy to identify narrow QTLs and construct the network of correlations that exists between DNA sequence, gene expression values, and ethanol-related phenotypes to prioritize our list of positional candidate genes. We observed large amounts of phenotypic variation with the DO population and identified suggestive and significant QTLs associated with ethanol sensitivity on chromosomes 1, 2, and 16. The implicated regions were narrow (4.5-6.9 Mb in size) and each QTL explained ~4-5% of the variance. Our results can be used to identify alleles that contribute to AUD in humans, elucidate causative biological mechanisms, or assist in the development of novel therapeutic interventions.


Sex differences in the pattern of esterase-active antigens in microsomes from various rat strains.
Esterase-active antigens present in male and female liver microsomes isolated from three different rat strains-(Sprague-Dawley, Wistar and Dark Agouti) were characterized in crossed immunoelectrophoresis in combination with a zymogram method for esterase activity. No qualitative but some quantitative differencies were encountered between the sexes. Thus, two out of ten antigens were present in significantly lower and one in significantly higher concentrations in male than in female microsomes, demonstrating that although the overall esterase activity in liver may be similar for males and females, the concentration of the individual antigens does vary between the sexes. No qualitative or quantitative differences in the pattern of esterase-active antigens were found between the different strains.


Plerixafor use in New Zealand 2016-2019: an observational study.
Plerixafor is used to mobilise CD34-positive stem cells for autologous transplantation to treat haematological malignancy. Funded in New Zealand since 2016, plerixafor can be used 'pre-emptively' to salvage a failing first attempt or as a 'rescue' strategy involving re-mobilising after 4 weeks. The rate of failed mobilisation and plerixafor uptake in New Zealand is not known, while international practice varies widely. To establish success rates for conditioning regimes used in New Zealand. We reviewed 203 consecutive patients with myeloma (n = 122) or lymphoma (n = 81) undergoing stem cell mobilisation between 1 January 2016 and 5 August 2019 at Christchurch hospital. We recorded demographics, conditioning regimens, harvest outcome and apheresis duration. Successful harvest was defined as collection of >2 × 106 CD34+ cells/kg. Seventeen percent of patients received plerixafor. Harvest success rates for lymphoma and myeloma respectively were 77% and 86% with standard conditioning, 95% and 100% with 'pre-emptive' plerixafor and 71% and 89% with 'rescue' plerixafor. 'Pre-emptive' plerixafor was non-inferior to standard conditioning. Following local guidelines resulted in at least one successful harvest for 96% lymphoma and 99% myeloma patients. Plerixafor strategies in New Zealand allow successful stem cell mobilisation for ≥96% of patients. Further research is required to investigate whether increased use would be cost-effective through reduced chemotherapy and apheresis duration, and improved graft quality.


ATRA ameliorates fibrosis by suppressing the pro-fibrotic molecule Fra2/AP-1 in systemic sclerosis.
Systemic sclerosis (SSc) is an autoimmune connective tissue disease that leads to irreversible fibrosis of the skin and the internal organs. The etiology of SSc is complex, its pathophysiology is poorly understood, and clinical therapeutic options are restricted. Thus, research into medications and targets for treating fibrosis is essential and urgent. Fos-related antigen 2 (Fra2) is a transcription factor that is a member of the activator protein-1 family. Fra2 transgenic mice were shown to have spontaneous fibrosis. All-trans retinoic acid (ATRA) is a vitamin A intermediate metabolite and ligand for the retinoic acid receptor (RAR), which possesses anti-inflammatory and anti-proliferative properties. Recent research has demonstrated that ATRA also has an anti-fibrotic effect. However, the exact mechanism is not fully understood. Interestingly, we identified potential binding sites for the transcription factor RARα to the promoter region of the FRA2 gene through JASPAR and PROMO databases. In this study, the pro-fibrotic effect of Fra2 in SSc is confirmed. SSc dermal fibroblasts and bleomycin-induced fibrotic tissues of SSc animals exhibit increased levels of Fra2. Inhibition of Fra2 expression in SSc dermal fibroblasts with Fra2 siRNA markedly decreased collagen I expression. ATRA reduced the expressions of Fra2, collagen I, and α-smooth muscle actin(α-SMA) in SSc dermal fibroblasts and bleomycin-induced fibrotic tissues of SSc mice. In addition, chromatin immunoprecipitation and dual-luciferase assays demonstrated that retinoic acid receptor RARα binds to the FRA2 promoter and modulates its transcriptional activity. ATRA decreases collagen I expression both in vivo and in vitro via the reduction of Fra2 expression. This work establishes the rationale for expanding the use of ATRA in the treatment of SSc and indicates that Fra2 can be used as an anti-fibrotic target.


Evaluation of a continuous noninvasive blood pressure monitor in obstetric patients undergoing spinal anesthesia.
A noninvasive blood pressure monitor (Finapres) that continuously displays the arterial waveform using the Penaz methodology has recently been introduced into clinical practice. We compared this device with an automated oscillometric blood pressure monitor (Dinamap 1846SX) in 20 patients during spinal anesthesia for nonemergency cesarean section according to a procedure suggested by the Association for the Advancement of Medical Instrumentation. After administration of the spinal anesthetic, the Finapres monitor produced systolic, mean, and diastolic pressure measurements greater than those of the Dinamap monitor (6.6 +/- 12.5, 3.3 +/- 10.4, and 7.2 +/- 9.8 mm Hg, respectively). In most patients, the Finapres measurements were similar to those determined by the Dinamap; however, in 4 patients, mean systolic differences were greater than 20 mm Hg. These patients did not differ from the others in age, height, weight, or baseline blood pressure, and the pressure values recorded by the Finapres monitor were substantially higher than those measured by auscultation in the labor room. In 30% of the patients, the offset between Dinamap and Finapres blood pressure measurements changed markedly over the course of the surgical procedure. The Finapres monitor occasionally stopped working and had to be restarted. In 1 patient (not included in this analysis), the Dinamap monitor was unable to determine the blood pressure due to patient shivering; this did not appear to interfere with the Finapres. We conclude that the Finapres monitor does not consistently provide blood pressure information equivalent to that of the Dinamap in obstetric patients undergoing spinal anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression in mammalian cells, purification and characterization of recombinant human pancreatic ribonuclease.
A synthetic cDNA coding for human pancreatic RNase, equipped with a secretion signal sequence, was cloned and stably expressed in Chinese hamster ovary cells. The recombinant RNase, secreted into the culture medium, was purified and characterized. It was found to be indistinguishable, by structural and catalytic parameters, from the enzyme isolated from human pancreas. Furthermore, the glycosylated forms were separated from the non-glycosylated form. Up until now, human RNases have been isolated only in small amounts from autopic specimens. This has hindered the exploitation of a human RNase for the construction of immunotolerated immunotoxins. On the other hand, the availability of an effective system for the expression of a human RNase may render feasible the transfer, by protein engineering, of the interesting pharmacological actions of non-human RNase [1993 Trends Cell Biol. 3, 106-109] to an immunotolerated, human RNase.


F-18 FDG PET/CT findings of metastatic ovarian tumors from gastrointestinal tract origin.
To review the F-18 FDG PET/CT findings of metastatic ovarian tumors and to determine any correlation between FDG uptake by metastatic ovarian tumors and that by the primary tumors. PET/CT performed from June 2005 to March 2011 on patients with metastatic ovarian tumors of gastrointestinal tract origin malignancies was analyzed retrospectively. The SUV(max) of metastatic ovarian tumors and primary tumors, when available, was measured. Thirty-two patients were included. Of the 32 cases, 20 had metastatic tumors in bilateral ovaries and 12 had in a single ovary. The mean SUV(max) of the 52 total lesions was 4.1 ± 3.1 (range 1.2-13.3), and 46 lesions showed a heterogeneous FDG uptake pattern. In 22 cases with available primary tumor SUV(max) values, there was a moderate positive correlation with the SUV(max) of the corresponding metastatic tumors (r = 0.559, p = 0.007). There was no significant correlation between the size and SUV(max) of metastatic ovarian tumors (p = 0.128). The mean SUV(max) of metastatic ovarian tumors from colorectal cancers was significantly higher than that of stomach cancers (p = 0.039). Metastatic ovarian tumors showed FDG uptake of variable intensity, depending on the primary tumor type. The FDG uptake pattern was heterogeneous by PET imaging in vast majority of the cases. When the primary tumor demonstrates a low FDG uptake, careful evaluation is necessary since the metastatic ovarian tumors may also show low FDG uptake.


Epidemiology of special incidents: Results from national mortality and morbidity registry and the associated factors in Iran in 2014.
Special incidents are harmful events that can result in people's death or injury. Despite registering special incidents' data in Iran, no study has yet been conducted to identify the types, rates, mortality and morbidity of such incidents and their associated factors. The present study was conducted to assess the epidemiology of incidents and their associated factors during 2014 in Iran. In this cross-sectional study, all special incidents of 2014 were examined. Data were initially collected by universities of medical sciences nationwide and then sent to the Disaster and Emergency Management Center in the Ministry of Health and Medical Education. The collected data were analyzed in this study using statistical tests of Chi-square and Pearson's correlation coefficient using SPSS ver. 14.5. Out of 6,892 special incidents that occurred during 2014 in Iran, 6,781 cases were included, of which, the most prevalent were traffic crashes (71%), carbon monoxide poisoning (14%), drowning (3.5%), and other cases (11.5%) (which included suspicious deaths, explosions, group poisoning, quarrels, fires, falls from height, and building collapses). The incidents led to 37,313 injuries and 3,259 deaths, of which 78% of injuries and 75% of deaths were due to road traffic incidents. Given to relationship between occurrence of the incidents and special holidays; such incidents can be reduced through preventive planning and education. We recommend annual monitoring of special incidents and further studies on the associated factors.


Scleral Fixation of Intraocular Lens in Aphakic Eyes without Capsular Support: Description of a New Technique.
To study the efficacy and safety of a modified trans-scleral intraocular lens (IOL) fixation technique in aphakic eyes when performed by ophthalmologists in training. The study was conducted in an institutional setting that included 43 surgeries performed by surgeons training in small incision cataract surgeries. The data were analyzed for stability and position of IOL, refractive changes, best-corrected vision, and associated complications. Mean age of the subjects was 53.8 ± 18.5yrs (range 6-81yrs). Surgical aphakia (58.14%) was the most common cause. The corrected distance visual acuity improved significantly at six weeks (p = 0.0003). The mean residual spectacle correction was +0.74 ± 1.2D spherical equivalent (cylinder -1.6±1.5D at 84 ± 50°) at the 6th-month follow-up (24.35 ± 6.71wks). Lens tilt on ultrasound biomicroscopy (kappa 0.762; p < 0.001) and the IOL centration (kappa 0.411; p = 0.001), assessed by two independent masked observers, were satisfactory at the 6th-month visit. Transient postoperative vitreous hemorrhage was the most common complication (46.5%). Cellular deposits on the IOL surface (18.6%), cystoid macular edema (11.6%), subconjunctival haptic exposure (4.66%), and haptic slippage (2.33%) were the other complications. This method of trans-scleral IOL fixation is an effective rescue procedure for eyes with deficient capsular support when ophthalmologists perform in training.


Spin Photochemistry: Electron Spin Multiplicity as a Tool for Reactivity and Selectivity Control.
Spin chemistry involving small organic molecules without heavy atoms is highly sensitive to spin-orbit-coupling (SOC) modulating biradical conformation as well as hyperfine coupling (HFC) modulating magnetic isotope interactions. Several easily available reaction properties such as chemo-, regio-, and diastereoselectivity as well as quantum yields serve as analytical tools to follow intersystem crossing (ISC) dynamics and allow titrating spin selectivities.


Enamel demineralization by snack foods.
The amount of enamel destroyed by salivary fermentation of snack foods and confections was not dependent on their sugar content; starch, flavoring agents, and other components also played a part. Most enamel destruction was produced by fruit-flavored candies in which the inherent acid or high sugar concentration or both inhibited bacterial fermentation.


Primary mucosal malignant melanoma: an immunohistochemical study of 12 cases with comparison to cutaneous and metastatic melanomas.
Immunohistochemical analysis of 40 formalin-fixed, paraffin-embedded malignant melanomas (12 primary mucosal, 16 primary cutaneous, and 12 metastatic cutaneous) was performed to study the possible differences in immunostaining profiles according to location. The majority of melanomas were reactive with a polyclonal antibody to S100 protein (P-S100; 85%), a monoclonal melanoma-specific antibody (HMB-45; 88%), and a monoclonal antibody to vimentin (90%), and there were no differences in staining profiles for these antibodies by anatomic location. In contrast, while 13 of 16 cutaneous melanomas (81%) and ten of 12 metastatic melanomas (83%) were reactive with a monoclonal antibody to S100 protein (MoAb-079), only five of 12 mucosal tumors (42%) showed positive staining for MoAb-079. Similarly, 14 cutaneous melanomas (88%) and 11 metastatic melanomas (92%) showed positive staining for neuron specific enolase (NSE), while only four mucosal melanomas (33%) were NSE-positive. Of the 40 melanomas, all but two were reactive with either P-S100, MoAb-079, or HMB-45. These findings suggest that MoAb-079 and NSE may be less sensitive markers than P-S100 and HMB-45 for routinely processed mucosal melanomas as compared with cutaneous and metastatic tumors.


Studying biological vulnerability and heterogeneity--a long way ahead.
Common diseases are usually the consequence of a variety of etiologies. This rule applies, for example, to mental retardation and epilepsy. There is evidence that genetic factors influence the propensity to utilize alcohol on an addictive basis at two levels of interaction between the drug and the body. It is doubtful that psychiatric symptoms are specific for defined etiologies. Individuals who are heterozygous for autosomal-recessive alleles may show slight deviations toward the homozygous genotype. These findings are applied to a polygenic concept of psychiatric disorders. Data are presented that would be compatible with a slightly increased incidence of heterozygotes for Wilson's disease and metachromatic leucodystrophy in psychiatric patients.


Hypertensive Emergencies: Implications for Nurses.
An acute elevation of blood pressure (BP) greater than 180/120 mm Hg associated with target organ damage is considered a hypertensive emergency. Patients with a hypertensive emergency need intravenous medications and close monitoring in the intensive care unit. Whereas an acute elevation of BP greater than 180/120 mm Hg without evidence of target organ damage is a hypertensive urgency. Patients with a hypertensive urgency are treated with oral medications and generally discharged home with outpatient follow-up. Patients with either condition need a thorough evaluation to determine cause of the acute increase in BP and education to optimize the treatment regimen long-term.


Autophagy suppression enhances DNA damage and cell death upon treatment with PARP inhibitor Niraparib in laryngeal squamous cell carcinoma.
Although poly (ADP-ribose) polymerase (PARP) inhibitors, as anti-tumor drugs targeting the DNA damage response (DDR), have been used for the therapy of various tumors, few researches reported their effect on laryngeal squamous cell carcinoma (LSCC). Here, we first discovered that the PARP-1/2 inhibitor Niraparib could simultaneously induce cell growth inhibition and autophagy in LSCC TU212 and TU686 cells. Niraparib decelerated cell cycle of LSCC by arresting G1 phase and preventing the cells from entering S phase. DNA lesions were also observed upon Niraparib treatment as evidenced by the accumulation of γH2AX and abatement of pRB expression. In addition, autophagy generation was confirmed by the observation of autophagosomes, LC3-positive autophagy-like vacuoles, and obvious conversion of LC3-I to LC3-II. Moreover, blocking autophagy enhanced Niraparib-induced growth inhibition and DNA lesions. Further studies suggested that autophagy suppression could obstruct the activation of checkpoint kinase 1 (Chk1) through elevating proteasomal activity and then impair the capacity of homologous recombination (HR), thereby improving the anti-LSCC efficiency of Niraparib. Collectively, these findings suggested that simultaneous targeting of Niraparib and autophagy might be a promising therapeutic schedule for LSCC in clinic.


Consistency and plausibility in epidemiologic analysis: application to breast cancer in relation to use of oral contraceptives.
Consistency and plausibility are fundamental criteria for judging cause and effect from observational studies. They are applied here to the interpretation of data from a population-based case-control study of oral contraceptives and breast cancer. A preliminary analysis of oral contraceptive use in young nulliparous women, who had no family history of either breast cancer or benign breast disease, showed a statistically significant dose-response, with long-term users (49 months or more) having an apparent 4-fold elevation in risk of early breast cancer. Further analyses, however, revealed striking inconsistencies which were biologically implausible. These effectively undermine cause and effect as an explanation for the initial finding.


A gigantic bizarre marine turtle (Testudines: Chelonioidea) from the Middle Campanian (Late Cretaceous) of South-western Europe.
Marine turtles were common in the subtropical Upper Cretaceous epi-continental seas that once washed the coasts of the ancient European archipelago. But unlike its contemporaneous faunas from North America, in Europe no taxon surpassed the 1.5 m shell-length. Here, the remains of a new large marine turtle, Leviathanochelys aenigmatica gen. et sp. nov., from the Middle Campanian of the Southern Pyrenees are described. Anatomical and histological evidence concur in identifying the specimen as a basal chelonioid. The new taxon autapomorphically differs from other marine turtles by possessing an additional process on the anteromedial side of the pelvis, and an acetabulum directed strongly ventrally. Based on the pelvis size, it is likely that Leviathanochelys was as large as Archelon, thus becoming one of the largest marine turtles found to ever exist. The large body size of the new taxon could have evolved as a response to the unique habitat conditions of the European Cretaceous archipelago seas. The presence of the accessory pubic process further suggests the occurrence of an additional insertion point of the Musculus rectus abdominis, which together with the paleohistologic evidences support the hypothesis that the new taxon had an open marine pelagic lifestyle.


Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock.
During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock. A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge (0, 5, 10, and 15 mug/kg/min) in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine. In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating variable for survival with the systolic blood pressure/left ventricular end-systolic volume index ratio alone among all other variables significantly improving the model. Survivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population.


Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.
Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).


Successful transfer of a bovine embryo through a cannulated fallopian tube.
The fallopian tubes of a recipient cow were surgically cannulated and the cannulae brought out through the flank. Two fertilised eggs, recovered surgically from a donor cow, were transferred to the uterus of the recipient cow through the cannulae. The recipient became pregnant and gave birth to a live normal female calf 289 days after the transfer. After the birth of the calf one cannula was found to be patent.


Structural analysis and knock-out of a Burkholderia pseudomallei homolog of the eukaryotic transcription coactivator PC4.
Homologs of the eukaryotic transcription coactivator PC4, which also functions in DNA repair and oxidative stress, were recently identified in prokaryotes. Crystallographic analysis of BPSL1147, a putative homolog from the pathogen Burkholderia pseudomallei K96243, reveals a highly conserved core structure and suggests a nucleic acid binding mode similar to that of PC4. Knock-out and complementation experiments do not reveal distinguishing phenotypes under normal growth conditions or in the presence of H2O2, arguing against a critical role in repair or the oxidative stress response of Burkholderia. These results may reflect redundancy or point at a bacteriophage origin of Burkholderia PC4 homologs.


Do the pigments differ chemotaxonomically fungi belonging to genusFusarium?
Biosynthesis of bikaverin - red pigment responsible for characteristic colour ofFusarium cultures and known as vacuolation and aging factor - by 60Fusarium isolates belonging to 9 species was examined. We observed that bikaverin is a common metabolite produced by species of Liseola, Mar tiella, Elegans and Dlaminiella sections.Twenty nine isolates of fourFusarium species (F. moniliforme, F. subglutinans, F. proliferatum andF. anthophilum), belonging to the following Liseola section were investigated on their ability to biosynthesis of secondary metabolites bikaverin, 8-methylfusarubin, 3,8-dimethylfusarubin, 8-methylbostrycoidin, nectriafurone and fusarin C. All examined isolates of section Liseola formed bikaverin and 8-methylfusarubin, while 21 isolates additionally produced 8-methylbostrycoidin. OnlyF. moniliforme isolates were able to form fusarin C. We did not observe chemotaxonomical differences betweenFusarium, species according their ability to biosynthesis of such secondary metabolites as bikaverin, 8-methylfusarubin and 8-methylbostrycoidin.


Reducing the undesirable odor of barley by cooking with superheated steam.
Superheated steam was used to cook barley and the volatile odor compounds and release of odorants from the steamed barley were analyzed. The main odor compounds in cooked barley were aldehydes (hexanal and (E,E)-2,4-decadienal) and acids (acetic acid and hexanoic acid). Compared to ordinary cooked barley, barley cooked by superheated steam had less odorants, and the release of odorants was reduced by almost half. Sensory evaluation revealed that this barley was preferred to ordinary cooked barley, because it had weaker smell and tasted less sour and less bitter. The steaming process steam distils and eliminates some odor compounds, while some water-soluble compounds (mainly acids) are washed away by water during steaming. Therefore, this steam cooking method, applied to barley for the first time here using a comprehensive analysis, improves the acceptability and palatability of this high-quality food rich in dietary fiber.


Total aneuploidy and age-related sex chromosome aneuploidy in cultured lymphocytes of normal men and women.
In PHA-cultured lymphocytes, about 8% of metaphases from 32 women were aneuploid compared to 4% of metaphases from 35 men. A significant part of this aneuploidy was characterized by sex chromosome involvement: in women, the loss of gain of X chromosomes; in men, the gain of X chromosomes and the loss or gain of Y chromosomes. The incidence of this aneuploidy was positively age-related for both sexes. Premature division of the X-chromosome centromere was closely associated with X-chromosome aneuploidy in women and men, and appeared to be the mechanism of non disjunction causing this aneuploidy. Premature centromere division (PCD) indicated a dysfunction of the X-chromosome centromere with aging, and this dysfunction was the basic cause of age-related aneuploidy. A similar mechanism of nondisjunction may operate for the Y chromosome of men, but could not be clearly demonstrated because of the low incidence of Y-chromosome aneuploidy. The balance of the aneuploidy was characterized by chromosome loss and the involvement of all chromosome groups. It was consistent with chromosome loss from metaphase cells damaged during preparation for cytogenetic examination.


Icariside Ⅱ attenuates bleomycin-induced pulmonary fibrosis by modulating macrophage polarization.
Numerous studies have provided evidence supporting the significant roles of icariin, in the prevention of multiple chronic diseases like diabetes, liver fibrosis, cardiac fibrosis, renal fibrosis, and pulmonary fibrosis. In particular, Icariside II (ISE II), a prominent flavonoid glycoside derived from Epimedium brevicornum Maxim, the principal metabolite of icariin, has demonstrated noteworthy anti-inflammatory and anti-oxidant properties, along with its ability to protect against lung remodeling. However, the research exploring ISE Ⅱ's application in treating pulmonary fibrosis remains limited. The aim of this study was to assess the therapeutic efficacy of ISE II in models of pulmonary fibrosis, while also investigating its potential mechanisms of action in cell signaling pathways. An in vitro model of pulmonary fibrosis was established by treating NIH-3T3 cells with transforming growth factor-β1 (TGF-β1). Western blot, RT-qPCR, and scratch test were performed to assess the effect of ISE Ⅱ. In addition, a murine model of pulmonary fibrosis was induced by intratracheal instillation of bleomycin, and the therapeutic effect of ISE Ⅱ was tested by orally administering ISE Ⅱ at a dose of 10 mg/kg. Three weeks later, lung function, micro-CT, hydroxyproline content, pathological staining, and cytokines detection of BALF or serum were used to assess the anti-fibrosis effects of ISE Ⅱ. Next, immunofluorescence staining, flow cytometry, and in vivo transcriptomics were used to investigate the underlying mechanisms of action. Our data revealed a significant inhibitory effect of ISE Ⅱ on the upregulation of α-smooth muscle actin (α-SMA) and collagen production induced by TGF-β1 in fibroblasts. Meanwhile, ISE Ⅱ exerted a therapeutic effect against bleomycin-induced pulmonary fibrosis in mice by improving lung function, decreasing collagen deposition, and reducing the expression of interleukin (IL)-1β, tumor necrosis factor α (TNF-α), TGF-β1 and platelet-derived growth factor (PDGF) in serum and bronchoalveolar lavage fluid (BALF). Additionally, ISE Ⅱ treatment effectively attenuated the infiltration of M2 macrophages, concurrently downregulating the expression level of M2 marker genes, such as CD206, arginase-1(Arg-1), and Chitinase-Like Protein 3 (YM-1). Importantly, we observed a statistically significant reduction in the M2 phenotype of interstitial macrophages (IMs). However, the impact of ISE Ⅱ on the M2 polarization of alveolar macrophages (AMs) did not reach statistical significance. Lastly, transcriptome sequencing results suggested that the anti-pulmonary fibrosis effects of ISE Ⅱ may be mediated by the suppression of the WNT/β-catenin signaling pathway, which modulated M2 polarization in macrophages and contributed to the amelioration of pulmonary fibrosis. By immunohistochemical analysis, it was verified that ISE Ⅱ treatment dramatically inhibited the activation of β-catenin in fibrosis murine. Our findings indicated that ISE Ⅱ exerted anti-fibrotic effects by inhibiting pro-fibrotic macrophage polarization. The underlying mechanism of action might be mediated by modulating the WNT/β-catenin signaling pathway to inhibit the M2 program in IMs.


Cytokines in Drosophila hematopoiesis and cellular immunity.
Hematopoiesis is a complex, multistep process in which progenitor cells undergo distinct cellular changes of proliferation and differentiation to give rise to mature blood cells in circulation. Many of the genetic and molecular events that drive these changes have been characterized in mammals, frogs, and zebra fish, and more recently in the insect model system Drosophila melanogaster. Blood cells in Drosophila are actively involved in fighting infections and the cellular immune responses are intimately tied to the process of hematopoiesis. In this article, we briefly review the fundamental similarities in Drosophila and mammalian hematopoiesis and highlight the potential roles of four cytokines/growth factors in Drosophila hematopoiesis and cellular immunity.