Ecological specialization in mycorrhizal symbiosis leads to rarity in an endangered orchid.
Terrestrial orchid germination, growth and development are closely linked to the establishment and maintenance of a relationship with a mycorrhizal fungus. Mycorrhizal dependency and specificity varies considerably between orchid taxa but the degree to which this underpins rarity in orchids is unknown. In the context of examining orchid rarity, large scale in vitro and in situ germination trials complemented by DNA sequencing were used to investigate ecological specialization in the mycorrhizal interaction of the rare terrestrial orchid Caladenia huegelii. Common and widespread sympatric orchid congeners were used for comparative purposes. Germination trials revealed an absolute requirement for mycorrhisation with compatibility barriers to germination limiting C. huegelii to a highly specific and range limited, efficacious mycorrhizal fungus. DNA sequencing confirmed fidelity between orchid and fungus across the distribution range of C. huegelii and at key life history stages within its life cycle. It was also revealed that common congeners could swap or share fungal partners including the fungus associated with the rare orchid but not vice versa. Data from this study provides evidence for orchid rarity as a cause and consequence of high mycorrhizal specialization. This interaction must be taken into account in efforts to mitigate the significant extinction risk for this species from anthropogenically induced habitat change and illustrates the importance of understanding fungal specificity in orchid ecology and conservation.


Effect of high-dose medroxyprogesterone acetate on tumor necrosis factor-alpha release in patients with chemotherapy-induced neutropenia.
The aim of the study was to investigate the effects of high-dose medroxyprogesterone acetate (MPA) on the tumor necrosis factor-alpha (TNF-alpha) release in patients with chemotherapy-induced neutropenia. We also evaluated the effects of high-dose MPA on hematological parameters (leukocyte, neutrophil, platelet, hemoglobin, hematocrit) and side effects of MPA. One week following the first cycle chemotherapy, 20 patients who developed neutropenia were enrolled in the study. One gram/day MPA was administered orally to the patients and was continued from one week following the first chemotherapy cycle to one week after the second chemotherapy cycle. The patients received the second chemotherapy cycle at the same dosages as the first cycle. Before MPA treatment TNF-alpha levels were lower than post-treatment levels, but the difference was not statistically significant (P > 0.05). The differences in the mean leukocyte and neutrophil counts before and after the high-dose MPA treatment were statistically significant (p < 0.05).


Use of the Geriatric Nutritional Risk Index to Assess Risk for Postoperative Complications Following Posterior Cervical Decompression/Fusion.
Posterior cervical decompression with or without fusion (PCD/F) is used to manage degenerative spinal conditions. Malnutrition has been implicated for poor outcomes in spine surgery. The aim of this study was to assess the ability of the Geriatric Nutritional Risk Index (GNRI) as a risk calculator for postoperative complications in patients undergoing PCD/F. The 2006 to 2018 American College of Surgeons National Surgery Quality Improvement Program Database was queried for patients undergoing PCD/F. Nutritional status was categorized as normal (GNRI greater than 98), moderately malnourished (GNRI 92-98), or severely malnourished (GNRI less than or equal to 92). Complications within 30 days of surgery were compared among the groups. Preoperative data that were statistically significant (P < 0.05) upon univariate χ2 analysis were included in the univariate then multivariate binary regression model to calculate adjusted ORs. All ORs were assessed at the 95% CI. Of the 7597 PCD/F patients identified, 15.6% were severely malnourished and 19.1% were moderately malnourished. Severe and moderate malnourishment were independent risk factors for mortality (OR = 3.790, 95% CI 2.492-5.763, P < 0.001; OR = 2.150, 95% CI 1.351-3.421, P = 0.011). Severe malnourishment was an independent risk factor for sepsis/septic shock (OR = 3.448, 95% CI 2.402-4.948, P < 0.001). In elderly patients undergoing PCD/F, severe malnutrition, as defined by the GNRI, was an independent risk factor for mortality and sepsis/septic shock. The GNRI may be more useful than other indices for risk stratification in elderly patients because it accounts for confounding variables such as hydration status and paradoxical malnourishment in obese patients.


Protein L. A bacterial Ig-binding protein that activates human basophils and mast cells.
Peptostreptococcus magnus strain 312 (10(6) to 10(8)/ml), which synthesizes a protein capable of binding to kappa L chains of human Ig (protein L), stimulated the release of histamine from human basophils in vitro. P. magnus strain 644, which does not synthesize protein L, did not induce histamine secretion. Soluble protein L (3 x 10(-2) to 3 micrograms/ml) induced histamine release from human basophils. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE): it was Ca2(+)- and temperature-dependent, optimal release occurring at 37 degrees C in the presence of 1.0 mM extracellular Ca2+. There was an excellent correlation (r = 0.82; p less than 0.001) between the maximal percent histamine release induced by protein L and that induced by anti-IgE, as well as between protein L and protein A from Staphylococcus aureus (r = 0.52; p less than 0.01). Preincubation of basophils with either protein L or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda-chains) blocked anti-IgE-induced histamine release but failed to block the histamine releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa-chains) blocked both anti-IgE- and protein L-induced releases, whereas human polyclonal IgG selectively blocked protein L-induced secretion. Protein L acted as a complete secretagogue, i.e., it activated basophils to release sulfidopeptide leukotriene C4 as well as histamine. Protein L (10(-1) to 3 micrograms/ml) also induced the release of preformed (histamine) and de novo synthesized mediators (leukotriene C4 and/or PGD2) from mast cells isolated from lung parenchyma and skin tissues. Intradermal injections of protein L (0.01 to 10 micrograms/ml) in nonallergic subjects caused a dose-dependent wheal-and-flare reaction. Protein L activates human basophils and mast cells in vitro and in vivo presumably by interacting with kappa L chains of the IgE isotype.


Hepatocellular carcinoma and liver pathology in tonga.
All liver histology records from Tonga during 1970-79 were reviewed, including 42 biopsy and one necropsy specimens. Primary hepatocellular carcinoma was the histological diagnosis in 13 (30 percent). The age standardised incidence rate for confirmed cases are: males 2.9 and females 1.5 per 100 000. These are unremarkable compared to some reported rates, but many of these areas have included a high percentage of unconfirmed cases. Other diagnosis included cirrhosis (14), cholangiocarcinoma (2), metastatic carcinoma (2), cholangitis (2), hepatic fibrosis (2), and actinomycosis (1). The difficulties of diagnosis and areas for further studies are discussed.


Turning your thesis into an article for Kai Tiaki Nursing Research.
Turning your thesis or work project into an article for NZNO's research magazine will ensure your findings reach a wider nursing audience.


Associations between 'valentine' heart shape, atrial enlargement and cardiomyopathy in cats.
'Valentine' heart shape is a common qualifier used in veterinary radiology to describe a cardiac silhouette with focal enlargement at the level of the base of the heart in feline patients. Anecdotally, this sign has been thought to be related to biatrial enlargement and also to hypertrophic cardiomyopathy (HCM). However, to our knowledge, there has been no study performed to assess the association between cardiac chamber enlargement and cardiac disease with the 'valentine'-shaped heart. The aim of this study was to verify the association between the 'valentine' heart shape observed in ventrodorsal thoracic radiographs and the presence of singular or combined cardiac chamber enlargement, and also the presence and type of cardiomyopathy (CM) in cats. A search of the database of the Small Animal Veterinary Hospital of the University of Florida for cats with a radiology report of thoracic radiographs that contained the words 'valentine' and 'biatrial', and echocardiography performed within 1 week, was undertaken; 41 cases met the inclusion criteria. Eighty-two percent of the cats of the study sample had some form of CM. The 'valentine' heart shape was associated with biatrial enlargement in 41% of the patients in our study sample that had some form of CM and just 8% of cases diagnosed with HCM, suggesting that the 'valentine' heart shape has a low association with HCM or biatrial enlargement; however, it should be considered a sign of feline CM.


Molecular, biochemical, and functional characterization of a Nudix hydrolase protein that stimulates the activity of a nicotinoprotein alcohol dehydrogenase.
The cytoplasmic coenzyme NAD(+)-dependent alcohol (methanol) dehydrogenase (MDH) employed by Bacillus methanolicus during growth on C(1)-C(4) primary alcohols is a decameric protein with 1 Zn(2+)-ion and 1-2 Mg(2+)-ions plus a tightly bound NAD(H) cofactor per subunit (a nicotinoprotein). Mg(2+)-ions are essential for binding of NAD(H) cofactor in MDH protein expressed in Escherichia coli. The low coenzyme NAD(+)-dependent activity of MDH with C(1)-C(4) primary alcohols is strongly stimulated by a second B. methanolicus protein (ACT), provided that MDH contains NAD(H) cofactor and Mg(2+)-ions are present in the assay mixture. Characterization of the act gene revealed the presence of the highly conserved amino acid sequence motif typical of Nudix hydrolase proteins in the deduced ACT amino acid sequence. The act gene was successfully expressed in E. coli allowing purification and characterization of active ACT protein. MDH activation by ACT involved hydrolytic removal of the nicotinamide mononucleotide NMN(H) moiety of the NAD(H) cofactor of MDH, changing its Ping-Pong type of reaction mechanism into a ternary complex reaction mechanism. Increased cellular NADH/NAD(+) ratios may reduce the ACT-mediated activation of MDH, thus preventing accumulation of toxic aldehydes. This represents a novel mechanism for alcohol dehydrogenase activity regulation.


Plasmid-mediated expression of the UmuDC mutagenesis proteins in an Escherichia coli strain engineered for human cytochrome P450 1A2-catalyzed activation of aromatic amines.
The mutagenic actions of many chemicals depend on the activities of bacterial "mutagenesis proteins", which allow replicative bypass of DNA lesions. Genes encoding these proteins occur on bacterial chromosomes and plasmids, often in the form of an operon (such as umuDC or mucAB) encoding two proteins. Many bacterial strains used in mutagenicity testing carry mutagenesis protein genes borne on plasmids, such as pKM101. Our objective was to introduce mutagenesis protein function into Escherichia coli strain DJ4309. This strain expresses recombinant human cytochrome P450 1A2 and NADPH-P450 reductase and carries out the metabolic conversion of aromatic and heterocyclic amines into DNA-reactive mutagens. We discovered that many mutagenesis-protein plasmids severely inhibit the response of strain DJ4309 to 2-amino-3,4-dimethylimid-azo[4,5-f]quinoline (MeIQ), a typical heterocyclic amine mutagen. Among many plasmids examined, one, pGY8294, a pSC101 derivative carrying the umuDC operon, did not inhibit MeIQ mutagenesis. Strain DJ4309 pGY8294 expresses active mutagenesis proteins, as shown by its response to mutagens such as 1-nitropyrene and 4-nitroquinoline 1-oxide (4-NQO), and is as sensitive as the parent strain DJ4309 to P450-dependent mutagens, such as MeIQ and 1-aminopyrene.


Cannabis use and transition to psychosis in people at ultra-high risk.
Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder. Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes. Lifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n=98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ(2)1=10.971, p=0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ(2)1=1.061, p=0.303). In people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.


Thyroid hormone effects on beta-adrenergic receptors in isolated fat cells in rats.
The effect of thyroid hormones (thyroxine and triiodothyronine) on catecholamine receptors in isolated rat fat cells was investigated. Binding of (3H)isoproterenol and (3H)norepinephrine were increased by thyroid hormones. (3H)isoproterenol binding was more enhanced than (3H)norepinephrine binding. Triiodothyronine had a more potent effect than thyroxine. (3H)isoproterenol was used to estimate the number or affinity of beta-adrenergic receptors in rat fat cells treated with thyroid hormones. The binding sites for (3H)isoproterenol were the same in untreated and with triiodothyronine treated fat cells. The equilibrium dissociation constants (KD) for the interaction of receptors with (3H)isoproterenol were altered in thyroid hormone treated cells. There was a significant difference between the untreated and triiodothyronine treated fat cells in the affinity of beta-adrenergic receptor binding sites for (3H)isoproterenol. Thyroid hormone could alter negative cooperative site-to-site interaction among the binding sites for (3H)isoproterenol.


Morphology and locomotion of individual epithelial cells in culture.
The behaviour in culture of epithelial cells derived from chick embryo pigmented retina epithelium (PRE), corneal epithelium (CE) and epidermis has been studied using time-lapse cinemicrography. The analysis concentrated on the morphology and movement of individual isolated cells, lacking contacts with other cells, during a 24h period starting 1-3 h after the cells were plated out in primary cultures. Isolated cells from all three sources could change morphology and reversibly exhibited either a poorly spread or a well-spread morphology. While poorly spread, the different cell types all appeared similar and all blebbed vigorously. In contrast, while well spread, the cells did not bleb significantly but there were other differences between them. Well-spread CE cells were always polarized by the presence of a dominant leading lamella but well-spread PRE cells were always unpolarized. Well-spread epidermal cells exhibited both a polarized and an unpolarized morphology. The tendency of individual isolated cells to change morphology varied with cell type. PRE cells were the most stable. Nearly 80% of them retained the same morphology throughout the period of analysis and only 1% of them showed three or more changes in morphology during this period. In contrast, 22% of CE cells and 37% of epidermal cells showed three or more changes in morphology during the period of observation. Isolated cells of all three types spent a greater proportion of the time exhibiting a poorly spread morphology than they spent exhibiting any alternative well-spread morphology. The analysis revealed a relationship between the morphology of isolated cells and the speed of their locomotion. Only cells with a well-spread polarized morphology showed significant movement. CE and epidermal cells with this morphology moved three to four times faster than their counter-parts with a poorly spread morphology or, in the case of epidermal cells, with a well-spread but unpolarized morphology. Actively moving PRE cells were not seen and this correlates with the absence of cells with a well-spread polarized morphology from cultures of this type. These findings are discussed in the light of similar investigations of cell behaviour in other epithelial cell types and fibroblasts.


Loss of epithelial RelA results in deregulated intestinal proliferative/apoptotic homeostasis and susceptibility to inflammation.
NF-kappaB plays a central, proinflammatory role in chronic intestinal inflammation, yet recent work suggests a predominantly protective function for this transcription factor group in some cell types of the intestine. We herein describe the conditional deletion of the NF-kappaB RelA gene in murine intestinal epithelia and determine its function in homeostatic control of enterocyte proliferation/apoptosis and susceptibility to colonic inflammation. Mice lacking RelA in ileal and colonic enterocytes were born in expected Mendelian ratios, and RelA-null epithelia differentiated normally. Spontaneous intestinal disease and death occurred with low penetrance in neonates lacking epithelial RelA. IkappaBalpha and IkappaBbeta were significantly diminished in RelA-null epithelia, and endotoxin challenge revealed elevated p50 and c-Rel DNA binding activity as compared with controls. Deletion of RelA resulted in diminished expression of antimicrobial (defensin-related cryptdin 4, defensin-related cryptdin 5, RegIIIgamma) and antiapoptotic, prorestitution genes (Bcl-x(L), RegIV, IL-11, IL-18), and basal rates of epithelial apoptosis and proliferation were elevated. Mice lacking colonic RelA were sensitive to dextran sodium sulfate-induced colitis. Although experimental colitis enhanced proliferation in cells lacking RelA, sustained epithelial cell apoptosis precluded mucosal healing and decreased animal survival. We conclude that activation of RelA is required for homeostatic regulation of cell death and division in intestinal epithelia, as well as for protection from development of severe, acute inflammation of the intestine.


Cannabis use history and characteristics of quit attempts: a comparison study of treatment-seeking and non-treatment-seeking cannabis users.
Cannabis is the most commonly used illicit substance worldwide, and cannabis use disorders (CUDs) are correspondingly high. Increased demand for treatment and relatively low rates of positive clinical outcomes has led to a large scientific investment in the development of interventions for the treatment of CUD. Much of this research is conducted with cannabis users who are not seeking treatment at the time of study participation, and it is unknown whether these individuals are representative of those who seek treatment. This study contrasted samples of cannabis users participating in screening interviews for treatment and nontreatment research studies. Several differences between groups emerged: Treatment-seekers were more likely to be female (43% vs. 29%), older (33.4 vs. 29.7 years), and have longer cannabis use histories compared with non-treatment-seekers (p = .007). Treatment-seekers were more likely to report experiencing guilt after using cannabis and to feel that cannabis use has been a problem for them. Additionally, treatment-seekers reported a greater mean number of reasons for making a quit attempt, experiencing a greater number of withdrawal symptoms, and employing more coping strategies during prior quit attempts. Despite the aforementioned differences, the 2 groups were similar on several key characteristics, particularly with regards to current levels of cannabis use and related problems.


Food in the aetiology of cancer.
During recent years much evidence has accumulated indicating that diet and nutrition may be important in the aetiology of human cancer. This paper discusses some of the components of diet that have been implicated as both causative and protective agents. Total calorie intake and overnutrition have been associated with breast and uterine cancers, high fat intake with cancer of the breast and large bowel and nitrates with gastric cancer. High fibre intakes are suggested to protect against colo-rectal cancer, and vitamin A, selenium and vitamin E have been inversely associated with various cancers.


Probing specificities of alcohol acyltransferases for designer ester biosynthesis with a high-throughput microbial screening platform.
Alcohol acyltransferases (AATs) enables microbial biosynthesis of a large space of esters by condensing an alcohol and an acyl-CoA. However, substrate promiscuity of AATs prevents microbial biosynthesis of designer esters with high selectivity. Here, we developed a high-throughput microbial screening platform that facilitates rapid identification of AATs for designer ester biosynthesis. First, we established a microplate-based culturing technique with in situ fermentation and extraction of esters. We validated its capability in rapid profiling of the alcohol substrate specificity of 20 chloramphenicol acetyltransferase variants derived from Staphylococcus aureus (CATSa ) for microbial biosynthesis of acetate esters with various exogeneous alcohol supply. By coupling the microplate-based culturing technique with a previously established colorimetric assay, we developed a high-throughput microbial screening platform for AATs. We demonstrated that this platform could not only probe the alcohol substrate specificity of both native and engineered AATs but also identify the beneficial mutations in engineered AATs for enhanced ester synthesis. We anticipate the high-throughput microbial screening platform provides a useful tool to identify novel wildtype and engineered AATs that have important roles in nature and industrial biocatalysis for designer bioester production.


Snake venom constituents: biochemistry and toxicology (Part 1).
Complicated and mystifying as the snake envenomation process may appear, the toxic principles of snake venoms are biochemical entities that could be isolated, purified and characterized. In this review, the toxicological process of envenomation and the biochemical basis of venom toxicity are presented for those not directly involved in venom research but who nevertheless have an interest in snake venom poisoning.


Neural and humoral effects on hindlimb vascular resistance of ducks during forced submergence.
Circulating catecholamines increase by three orders of magnitude in forced submerged ducks; their role in promoting vascular resistance was studied using vascular perfusion of hindlimbs. Perfusion pressure and blood flow were recorded simultaneously in hindlimbs of ducks during forced submergence. One leg was perfused with blood mixtures devoid of catecholamines (test leg) and compared with the other autoperfused leg. Perfusion pressures in test legs perfused with hyperoxic and hypocapnic blood or with hypoxic and hypocapnic blood were not significantly different from those in the matching autoperfused legs. However, when test legs were perfused with hypercapnic blood, regardless of whether blood was hypoxic or hyperoxic, perfusion pressures were significantly lower than in autoperfused legs. Adding catecholamines to test legs perfused with hypoxic and hypercapnic blood, after 3 min submergence, significantly enhanced vasoconstriction. Hypercapnia acts directly on the peripheral vascular beds and impairs the neurally mediated vasoconstriction during submergence, while circulating catecholamines restore peripheral vasoconstriction. Thus circulating catecholamines are needed to compensate for the depressant action of hypercapnia on neurally mediated vasoconstriction.


Notch signaling induces either apoptosis or cell fate change in multiciliated cells during mucociliary tissue remodeling.
Multiciliated cells (MCCs) are extremely highly differentiated, presenting >100 cilia and basal bodies. Therefore, MCC fate is thought to be terminal and irreversible. We analyzed how MCCs are removed from the airway-like mucociliary Xenopus epidermis during developmental tissue remodeling. We found that a subset of MCCs undergoes lateral line-induced apoptosis, but that the majority coordinately trans-differentiate into goblet secretory cells. Both processes are dependent on Notch signaling, while the cellular response to Notch is modulated by Jak/STAT, thyroid hormone, and mTOR signaling. At the cellular level, trans-differentiation is executed through the loss of ciliary gene expression, including foxj1 and pcm1, altered proteostasis, cilia retraction, basal body elimination, as well as the initiation of mucus production and secretion. Our work describes two modes for MCC loss during vertebrate development, the signaling regulation of these processes, and demonstrates that even cells with extreme differentiation features can undergo direct fate conversion.


[A case of Lissauer form of paretic neurosyphilis with drop attacks and dementia].
A 52-year-old man was admitted to our hospital due to drop attack accompanied with progressive right hand's clumsiness and recent memory impairment. Neurological examination revealed postural involuntary movement of the right hand, and impaired finger fine movements. He showed mild mental deterioration with lower MMSE score. Toreponema Pallidum Latex immuno Assay (TPLA) titers in serum and cerebrospinal fluid (CSF) were remarkably elevated. MRI revealed cerebral atrophy in the left hemisphere. The 99mTc-ECD SPECT analysis showed reduced cerebral blood flow in the left hemisphere. EEG showed slow background activity in the left hemisphere. Drop attacks and involuntary movement were diminished by the administration of the valproate. We diagnosed this case as Lissauer's general paresis and treated with intravenous benzylpenicillin potassium 24 million units per day for 2 weeks. After this treatment, the titer of TPLA in the serum and CSF decreased. The clinical symptoms and signs, the score of MMSE, findings of SPECT and EEG also improved. Although Lissauer's general paresis is a rare form of neurosyphilis, it is important to distinguish this disease in case of progressive dementia and focal neurological signs. Early diagnosis and treatment are the only way to prevent irreversible neurological damage in this disease.


NADPH oxidase mediates depressive behavior induced by chronic stress in mice.
Stress is a potent risk factor for depression, yet the underlying mechanism is not clearly understood. In the present study, we explored the mechanism of development and maintenance of depression in a stress-induced animal model. Mice restrained for 2 h daily for 14 d showed distinct depressive behavior, and the altered behavior persisted for >3 months in the absence of intervention. Acute restraint induced a surge of oxidative stress in the brain, and stress-induced oxidative stress progressively increased with repetition of stress. In vitro, the stress hormone glucocorticoid generated superoxide via upregulation of NADPH oxidase. Consistently, repeated restraints increased the expression of the key subunits of NADPH oxidase, p47phox and p67phox, in the brain. Moreover, stressed brains markedly upregulated the expression of p47phox to weak restress evoked in the poststress period, and this molecular response was reminiscent of amplified ROS surge to restress. Pharmacological inhibition of NADPH oxidase by the NADPH oxidase inhibitor apocynin during the stress or poststress period completely blocked depressive behavior. Consistently, heterozygous p47phox knock-out mice (p47phox(+/-)) or molecular inhibition of p47phox with Lenti shRNA-p47phox in the hippocampus suppressed depressive behavior. These results suggest that repeated stress promotes depressive behavior through the upregulation of NADPH oxidase and the resultant metabolic oxidative stress, and that the inhibition of NADPH oxidase provides beneficial antidepression effects.


Methane uptake in forest soils along an urban-to-rural gradient in Pearl River Delta, South China.
We investigated soil CH4 fluxes from six forests along an urban-to-rural gradient in Guangzhou City metropolitan area, South China. The most significant CH4 consumption was found in the rural site, followed by suburban, and then urban forest sites. The rates of CH4 uptake were significantly higher (by 38% and 44%, respectively for mixed forest and broadleaf forest) in the rural than in the urban forest site. The results indicate that soil water filled pore space (WFPS) is the primary factor for controlling CH4 consumption in subtropical forests. The reductions of soil CH4 uptake in urban forests were also influenced by the higher rates of atmospheric nitrogen (N) deposition and increases in soil nitrate (NO3(-)) and aluminum (Al(3+)) contents as a result of urbanization. Results from this work suggest that environmental changes associated with urbanization could decrease soil CH4 consumption in subtropical forests and potentially contribute to increase of atmospheric CH4 concentration.


Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 for optimal inhibition of tumor necrosis factor-{alpha}-converting enzyme.
Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the matrix metalloproteinases, the ADAMs (a disintegrin and metalloproteinase) and the ADAM-TS (ADAM with thrombospondin repeats) proteinases. There are four mammalian TIMPs (TIMP-1 to -4), and each TIMP has its own profile of metalloproteinase inhibition. TIMP-4 is the latest member of the TIMPs to be cloned, and it has never been reported to be active against the tumor necrosis factor-alpha-converting enzyme (TACE, ADAM-17). Here we examined the inhibitory properties of the full-length and the N-terminal domain form of TIMP-4 (N-TIMP-4) with TACE and showed that N-TIMP-4 is a far superior inhibitor than its full-length counterpart. Although full-length TIMP-4 displayed negligible activity against TACE, N-TIMP-4 is a slow tight-binding inhibitor with low nanomolar binding affinity. Our findings suggested that the C-terminal subdomains of the TIMPs have a significant impact over their activities with the ADAMs. To elucidate further the molecular basis that underpins TIMP/TACE interactions, we sculpted N-TIMP-4 with the surface residues of TIMP-3, the only native TIMP inhibitor of the enzyme. Transplantation of only three residues, Pro-Phe-Gly, onto the AB-loop of N-TIMP-4 resulted in a 10-fold enhancement in binding affinity; the K(i) values of the resultant mutant were almost comparable with that of TIMP-3. Further mutation at the EF-loop supported our earlier findings on the preference of TACE for leucine at this locus. Drawing together our previous experience in TACE-targeted mutagenesis by using TIMP-1 and -2 scaffolds, we have finally resolved the mystery of the selective sensitivity of TACE to TIMP-3.


Identification of signal sequence binding proteins integrated into the rough endoplasmic reticulum membrane.
An azidophenacyl derivative of a chemically synthesized consensus signal peptide has been prepared. The peptide, when photoactivated in the presence of rough or high-salt-stripped microsomes from pancreas, leads to inhibition of their activity in cotranslational processing of secretory pre-proteins translated from their mRNA in vitro. The peptide binds specifically with high affinity to components in the microsomal membranes from pancreas and liver, and photoreaction of a radioactive form of the azidophenacyl derivative leads to covalent linkage to yield two closely related radiolabelled proteins of Mr about 45,000. These proteins are integrated into the membrane, with large 30,000-Mr domains embedded into the phospholipid bilayer to which the signal peptide binds. A smaller, endopeptidase-sensitive, domain is exposed on the cytoplasmic surface of the microsomal vesicles. The specificity and selectivity of the binding of azidophenacyl-derivatized consensus signal peptide was demonstrated by concentration-dependent inhibition of photolabelling by the 'cold' synthetic consensus signal peptide and by a natural internal signal sequence cleaved and isolated from ovalbumin. The properties of the labelled 45,000-Mr protein-signal peptide complexes, i.e. mass, pI, ease of dissociation from the membrane by detergent or salts and immunological properties, distinguish them from other proteins, e.g. subunits of signal recognition particle, docking protein and signal peptidase, already known to be involved in targetting and processing of nascent secretory proteins at the rough endoplasmic reticulum membrane. Although the 45,000-Mr signal peptide binding protein displays properties similar to those of the signal peptidase, a component of the endoplasmic reticulum, the azido-derivatized consensus signal peptide does not interact with it. It is proposed that the endoplasmic reticulum proteins with which the azidophenacyl-derivatized consensus signal peptide interacts to yield the 45,000-Mr adducts may act as receptors for signals in nascent secretory pre-proteins in transduction of changes in the endoplasmic reticulum which bring about translocation of secretory protein across the membrane.


Response of puppies to canine-origin parvovirus vaccines.
Pups 9-18 1/2 weeks old were given a single dose of 1 of 4 commercial, live, canine-origin parvovirus vaccines. All 4 vaccines evoked high levels of antibody in seronegative pups, but variable response in those with low levels of maternally derived antibodies. Vaccinal virus spread to unvaccinated contact controls and elicited essentially equivalent titers. No clinical signs of parvovirus infection were observed in vaccinates or controls.


Anaplastic ependymoma: treatment of pediatric patients with or without craniospinal radiation therapy.
The authors conducted a retrospective review of the clinical and treatment characteristics and outcomes in 28 pediatric patients with anaplastic ependymoma treated with radiation therapy since the advent of computerized tomography (CT) (1978-1994). Twelve patients received craniospinal irradiation followed by a boost to the primary site, two received whole-brain radiation therapy followed by a boost to the primary site, and the remaining 14 were treated with focal radiation therapy. The mean dose to the primary site was 5486 cGy. With a median follow-up period of 86 months for the 14 surviving patients (range 31-201 months), the median disease-free survival, measured from the date of diagnosis to the time of recurrence after radiation therapy, was 40 months. The median disease-free survival measured from the start of radiation therapy was 32 months. The median overall survival rate has not been reached and the actuarial estimates of overall survival rates at 5 and 10 years were 56% and 38%, respectively. According to univariate analysis, the disease-free survival rate was significantly improved (p < 0.01) in patients who underwent a gross-total resection at diagnosis. Overall survival rates were negatively influenced by treatment with craniospinal and whole-brain irradiation. As calculated by multivariate analysis, increasing dosage to the primary site (p < 0.05), infratentorial location (p < 0.01), and gross-total resections (p < 0.02) resulted in the longest disease-free survival times. All 19 patients in whom treatment failed after radiation therapy suffered a recurrence at the primary site. In addition, one of these patients experienced subarachnoid dissemination. Radiation treatment recommendations for patients with ependymoma have been based on the tumor's location, perceived risk for dissemination, and malignant propensity. The significance of anaplastic histological classification is controversial. Differences in the disease-free and overall survival rates have been demonstrated between ependymomas and anaplastic ependymomas treated in the pre-CT era. The results of this study show that there is no benefit from craniospinal irradiation in this group of patients.


1-O-vinyl glycosides via Tebbe olefination, their use as chiral auxiliaries and monomers.
A series of anomerically pure 1-O-formyl glycosides 1 was prepared and converted into the corresponding 1-O-vinyl glycosides 2 by Tebbe olefination. The unsubstituted vinyl glycosides were obtained as anomerically pure compounds in good yields, and the method of preparation was compatible with the presence of a variety of functional groups. Remarkably, the anomeric formate group was regioselectively converted into the corresponding olefin in the presence of acetate and benzoate protecting groups. With the perspective to use the 1-O-vinyl glycosides as monomers for the preparation of glycosylated poly(vinyl alcohol) derivatives with controlled tacticity, their scope as chiral auxiliaries for a stereodifferentiation in addition reactions to the olefin function was investigated by using the [2+2] cycloaddition to dichloroketene as a model reaction. In particular, vinyl 2,3,4,6-tetra-O-benzoyl-alpha-d-mannopyranoside (2i) exhibited excellent diastereoselectivity. Finally, the 1-O-vinyl glycosides were successfully subjected to radical homopolymerization in bulk or used as electron-rich comonomers in radical copolymerizations with maleic anhydride, yielding alternating, glycosylated poly(vinyl alcohol-alt-maleic anhydride).


AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD.
The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS) handling. We determined the requirement of AMP-activated protein kinase (AMPK) for exercise training-induced increases in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p < 0.01) and superoxide dismutase 2 (MnSOD; p < 0.05) protein abundance in quadriceps muscle of wild-type (WT; n = 13-15), but not AMPK α2 kinase dead (KD; n = 12-13) mice. We also observed a strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of healthy humans (p = 0.051; n = 6). To further elucidate a role for AMPK in mediating these effects, we treated WT (n = 7-8) and AMPK α2 KD (n = 7-9) mice with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). Four weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK α2 KD mice. We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n = 9-10). Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p < 0.05). Finally, the acetylation status of SIRT3 target lysine residues on MnSOD (K122) or oligomycin-sensitivity conferring protein (OSCP; K139) was not altered in either mouse or human skeletal muscle in response to acute exercise. We propose an important role for AMPK in regulating mitochondrial function and ROS handling in skeletal muscle in response to exercise training.


The family-oriented clinical simulation: an interdisciplinary tool for professional growth.
An interdisciplinary, educational technique--the family-oriented clinical simulation--is described and compared and contrasted to other commonly used role-playing techniques. Implications for training and supervision of physical therapists and other health care professionals are discussed, including the technique's relevance as a vehicle for studying in an applied clinical context the interface of physical disease and its psychosocial manifestations. The article concludes with a description of the benefits and potential disadvantages of the technique.


Sertoli-germ cell junctions in the testis: a review of recent data.
Spermatogenesis is a process that involves an array of cellular and biochemical events, collectively culminating in the formation of haploid spermatids from diploid precursor cells known as spermatogonia. As germ cells differentiate from spermatogonia into elongated spermatids, they also progressively migrate across the entire length of the seminiferous epithelium until they reach the luminal edge in anticipation of spermiation at late stage VIII of spermatogenesis. At the same time, these germ cells must maintain stable attachment with Sertoli cells via testis-unique intermediate filament- (i.e. desmosome-like junctions) and actin- (i.e. ectoplasmic specializations, ESs) based cell junctions to prevent sloughing of immature germ cells from the seminiferous epithelium, which may result in infertility. In essence, both desmosome-like junctions and basal ESs are known to coexist between Sertoli cells at the level of the blood-testis barrier where they cofunction with the well-studied tight junction in maintaining the immunological barrier. However, the type of anchoring device that is present between Sertoli and germ cells depends on the developmental stage of the germ cell, i.e. desmosome-like junctions are present between Sertoli and germ cells up to, but not including, step 8 spermatids after which this junction type is replaced by the apical ES. While little is known about the biology of the desmosome-like junction in the testis, we have a relatively good understanding of the molecular architecture and the regulation of the ES. Here, we discuss recent findings relating to these two junction types in the testis, highlighting prospective areas that should be investigated in future studies.


Predictors, Outcomes, and Statistical Solutions of Missing Cases in Web-Based Psychotherapy: Methodological Replication and Elaboration Study.
Missing cases present a challenge to our ability to evaluate the effects of web-based psychotherapy trials. As missing cases are often lost to follow-up, less is known about their characteristics, their likely clinical outcomes, or the likely effect of the treatment being trialed. The aim of this study is to explore the characteristics of missing cases, their likely treatment outcomes, and the ability of different statistical models to approximate missing posttreatment data. A sample of internet-delivered cognitive behavioral therapy participants in routine care (n=6701, with 36.26% missing cases at posttreatment) was used to identify predictors of dropping out of treatment and predictors that moderated clinical outcomes, such as symptoms of psychological distress, anxiety, and depression. These variables were then incorporated into a range of statistical models that approximated replacement outcomes for missing cases, and the results were compared using sensitivity and cross-validation analyses. Treatment adherence, as measured by the rate of progress of an individual through the treatment modules, and higher pretreatment symptom scores were identified as the dominant predictors of missing cases probability (Nagelkerke R2=60.8%) and the rate of symptom change. Low treatment adherence, in particular, was associated with increased odds of presenting as missing cases during posttreatment assessment (eg, odds ratio 161.1:1) and, at the same time, attenuated the rate of symptom change across anxiety (up to 28% of the total symptom with 48% reduction effect), depression (up to 41% of the total with 48% symptom reduction effect), and psychological distress symptom outcomes (up to 52% of the total with 37% symptom reduction effect) at the end of the 8-week window. Reflecting this pattern of results, statistical replacement methods that overlooked the features of treatment adherence and baseline severity underestimated missing case symptom outcomes by as much as 39% at posttreatment. The treatment outcomes of the cases that were missing at posttreatment were distinct from those of the remaining observed sample. Thus, overlooking the features of missing cases is likely to result in an inaccurate estimate of the effect of treatment.


Continuous monitoring of temperature and freshness in cold chain transport based on the dual-responsive fluorescent hydrogel.
Comprehensive attention should be paid to the potential food spoilage in food transport. However, there is a problem of freshness destruction by repeated freezing and thawing during the cold chain transport. Herein, a fluorescent hydrogel with N-doped green-emitting carbon dots (N-GCDs), bovine serum albumin-gold nanoclusters (BSA-AuNCs) as fluorescent probes and polyvinyl alcohol-sodium alginate hydrogel as carrier matrix was developed to continuously detect temperature and freshness. Due to the solvatochromic effect of N-GCDs, when the temperature surpassed the threshold, the mixture of water and dimethyl sulfoxide underwent a phase transition and melted into the gel, changing the fluorescence color to realize the temperature monitoring. Then, due to the pH effect of BSA-AuNCs, the gel could respond to pH changes in food deterioration to monitor the food freshness. Thus, the changes of both fluorescence color and intensity of the hydrogel provides a new method for visual and portable authenticity of food freshness.


Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and pyridoxal are prodrugs.
Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is unknown. This was a pre-specified substudy of a randomized, placebo-controlled trial comparing the antiemetic effect of the doxylamine-vitamin B6 combination (Diclectin®) (n = 131) to placebo (n = 126) in women with nausea and vomiting of pregnancy. Serum concentrations of pyridoxine, pyridoxal, and pyridoxal 5' phosphate (PLP) and doxylamine were measured on Days 4, 8, and 15. With Diclectin® exhibiting a significant antiemetic effect in pregnancy, serum concentrations of pyridoxine were unmeasurable in almost all patients and those of pyridoxal were undetectable in half of patients. In contrast, PLP was measurable at sustained, stable steady-state levels in all patients. Our data suggest that there is a correlation between PLP levels and PUQE score of morning sickness symptoms when pyridoxine and pyridoxal levels are undetectable, and hence they might be prodrugs of PLP, which may be the active antiemetic form of vitamin B6.


Modern neurosyphilis--a critical analysis.
Neurosyphilis remains a source of perplexity for today's physicians. Controversies exist over the interpretation of serologic tests, cerebrospinal fluid (CSF) abnormalities, diagnostic criteria, and treatment regimens. Its occurrence with human immunodeficiency virus (HIV) infection has raised fears of its recrudescence. A critical analysis of the evidence behind these viewpoints leads to several conclusions: the CSF VDRL is the most appropriate diagnostic test; pleocytosis is the only reliable CSF measure of disease activity; commonly accepted diagnostic criteria do not exclude nonsyphilitic disease; and treatment requires the prolonged use of parenteral penicillin, but no superior regimen has been found. Most data do not currently support the view that concurrent HIV infection produces accelerated or resistant neurosyphilis.


Intraventricular meningioma resection and visual outcomes.
Intraventricular meningiomas (IVMs) of the lateral ventricle are rare tumors that present surgical challenges because of their deep location. Visual field deficits (VFDs) are one risk associated with these tumors and their treatment. VFDs may be present preoperatively due to the tumor and mass effect (tumor VFDs) or may develop postoperatively due to the surgical approach (surgical VFDs). This institutional series aimed to review surgical outcomes following resection of IVMs, with a focus on VFDs. Patients who received IVM resection at one academic institution between the years 1996 and 2021 were retrospectively reviewed. Diffusion tensor imaging (DTI) reconstructions of the optic radiations around the tumor were performed from preoperative IVM imaging. The VFD course and resolution were documented. Thirty-two adult patients underwent IVM resection, with gross-total resection in 30 patients (93.8%). Preoperatively, tumor VFDs were present in 6 patients, resolving after surgery in 5 patients. Five other patients (without preoperative VFD) had new persistent surgical VFDs postoperatively (5/32, 15.6%) that persisted to the most recent follow-up. Of the 5 patients with persistent surgical VFDs, 4 received a transtemporal approach and 1 received a transparietal approach, and all these deficits occurred prior to regular use of DTI in preoperative imaging. New surgical VFDs are a common neurological deficit after IVM resection. Preoperative DTI may demonstrate distortion of the optic radiations around the tumor, thus revealing safe operative corridors to prevent surgical VFDs.


Fetal beat detection in abdominal ECG recordings: global and time adaptive approaches.
We present a method for location of fetal QRS in maternal abdominal ECG recordings. This method's initial, global approach was proposed in the context of the 2013 PhysioNet/Computing in Cardiology Challenge where it was tested on the 447 four channel one-minute recordings.The first step is filtering to eliminate baseline wander and high frequency noise. Upon detection, maternal QRS is removed on each channel using a filter applied to the other three channels. Next we locate fetal QRS on each channel and select the channel with the best set of detections. The method was awarded the third-best score in the Challenge event 1 with 278.755 (beats/minute) and the fourth-best score on event 2 with 28.201 ms.The 5 min long recordings of the Abdominal and Direct Fetal ECG Database were used to further test the method. This database contains five recordings obtained from women in labor. Results in these longer recordings were not satisfactory. This appears to be particularly the case in recordings with a more clearly non-stationary nature. In a new approach to our method, some changes are introduced. Two features are updated over time: the filter used to eliminate maternal QRS and the channel used to detect fetal beats. These changes significantly improved the QRS detection performance on longer recordings, but the scores on the 1 minute Challenge recordings were degraded.


Rylene and related diimides for organic electronics.
Organic electron-transporting materials are essential for the fabrication of organic p-n junctions, photovoltaic cells, n-channel field-effect transistors, and complementary logic circuits. Rylene diimides are a robust, versatile class of polycyclic aromatic electron-transport materials with excellent thermal and oxidative stability, high electron affinities, and, in many cases, high electron mobilities; they are, therefore, promising candidates for a variety of organic electronics applications. In this review, recent developments in the area of high-electron-mobility diimides based on rylenes and related aromatic cores, particularly perylene- and naphthalene-diimide-based small molecules and polymers, for application in high-performance organic field-effect transistors and photovoltaic cells are summarized and analyzed.


BCG Vaccination Status, Age, and Gender as Risk Factors for Leprosy in Endemic Areas in the Brazilian Amazon.
In 2018, 208,619 new cases of leprosy were reported to the World Health Organization (WHO). Of these, 30,957 occurred in the Americas region and 28,660 (92.6% of the total in the Americas) were reported in Brazil. This study aimed to show the reality of the profile of a population in an endemic leprosy area in northern Brazil in relation to age, gender, and bacillus Calmette-Guérin (BCG) vaccination status through the collection of data in the field with the evaluation of the study individuals, who were recruited by spontaneous demand. A total of 405 individuals participated in the study, with 100 multibacillary, 57 paucibacillary, and 248 healthy contacts. A relationship was observed between the occurrence of the disease, as well as the multibacillary form with the largest age group. The male gender was associated with leprosy per se, with the multibacillary form and was the largest representative of the group that was not vaccinated once. BCG vaccination was effective both in protecting against leprosy per se and in the multibacillary form. These results are limited by sample size, may not be conclusive, and will need further confirmation in a larger cohort.


Seabird species vary in behavioural response to drone census.
Unmanned aerial vehicles (UAVs) provide an opportunity to rapidly census wildlife in remote areas while removing some of the hazards. However, wildlife may respond negatively to the UAVs, thereby skewing counts. We surveyed four species of Arctic cliff-nesting seabirds (glaucous gull Larus hyperboreus, Iceland gull Larus glaucoides, common murre Uria aalge and thick-billed murre Uria lomvia) using a UAV and compared censusing techniques to ground photography. An average of 8.5% of murres flew off in response to the UAV, but >99% of those birds were non-breeders. We were unable to detect any impact of the UAV on breeding success of murres, except at a site where aerial predators were abundant and several birds lost their eggs to predators following UAV flights. Furthermore, we found little evidence for habituation by murres to the UAV. Most gulls flew off in response to the UAV, but returned to the nest within five minutes. Counts of gull nests and adults were similar between UAV and ground photography, however the UAV detected up to 52.4% more chicks because chicks were camouflaged and invisible to ground observers. UAVs provide a less hazardous and potentially more accurate method for surveying wildlife. We provide some simple recommendations for their use.


Pre- and post-conception pesticide exposure and the risk of birth defects in an Ontario farm population.
The use of pesticides has enhanced the health and economies of nations around the world by improving crop production. However, pesticides may pose health risks, particularly to the fetus and young children. In a secondary analysis of the Ontario Farm Family Health Study, we explored the relationship between birth defects and parental pesticide exposure during the 3 months prior to conception and the first trimester of pregnancy. A total of 3412 pregnancies were included in the study. Logistic regression fit by maximum likelihood was used in the analysis. The results showed that pre-conception exposure to both cyanazine (odds ratio=4.99, 95% confidence interval: 1.63-15.27) and dicamba (OR=2.42, 95% CI: 1.06-5.53) were associated with increased risk of birth defects in male offspring. Nevertheless, given the self-reported nature of the exposure and outcomes in this study, the present findings should be considered primarily as hypothesis generating, requiring verification in subsequent investigations.


Immunosuppression by combined use of cyclosporine and resveratrol in a rat liver transplantation model.
Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of intraperitoneal injection of cyclosporine (CsA) and resveratrol (Res) on allograft rejection after liver transplantation in rats. Male Sprague-Dawley rats were selected as donors and male Wistar rats as recipients for a rejection model. The recipients were divided into three groups after orthotopic liver transplantation (OLTx): in the combination group both Res (100 mg/kg) and CsA (20 mg/kg) were given by intraperitoneal route once a day, whereas in the CsA group or control group CsA (20 mg/kg) or vehicle buffer was given. The survival period, serum chemistry, production of some cytokines, activation of transcription factor NF- kappaB, and histopathological findings were then compared among them. The mean survival period after OLTx in the combination group was significantly longer than that in the CsA group or control group (P < .05 and P < .01). On posttransplant day 7, the serum albumin level significantly improved, the serum total bile acid and alanine aminotransferase levels were significantly lower, the serum interleukin-2 and interferon-gamma levels were significantly lower, and the activation of transcription factor NF-kappaB in peripheral blood T lymphocytes was significantly suppressed in the combination group in comparison with those in the CsA group (all P < .05) or control group (all P < .01), and a histological examination revealed apparent difference in the severity of rejection between the combination group and CsA group (P < .05) or control group (P < .01). The combined use of CsA and Res has a stronger immunosuppressive effect on hepatocytes under allograft rejection in comparison with the sole use of CsA. Res might serve as a novel supplementary immunosuppressive agent for reducing the severity of hepatic allograft rejection in rats.


Global health and climate change: moving from denial and catastrophic fatalism to positive action.
The health effects of climate change have had relatively little attention from climate scientists and governments. Climate change will be a major threat to population health in the current century through its potential effects on communicable disease, heat stress, food and water security, extreme weather events, vulnerable shelter and population migration. This paper addresses three health-sector strategies to manage the health effects of climate change-promotion of mitigation, tackling the pathways that lead to ill-health and strengthening health systems. Mitigation of greenhouse gas (GHG) emissions is affordable, and low-carbon technologies are available now or will be in the near future. Pathways to ill-health can be managed through better information, poverty reduction, technological innovation, social and cultural change and greater coordination of national and international institutions. Strengthening health systems requires increased investment in order to provide effective public health responses to climate-induced threats to health, equitable treatment of illness, promotion of low-carbon lifestyles and renewable energy solutions within health facilities. Mitigation and adaptation strategies will produce substantial benefits for health, such as reductions in obesity and heart disease, diabetes, stress and depression, pneumonia and asthma, as well as potential cost savings within the health sector. The case for mitigating climate change by reducing GHGs is overwhelming. The need to build population resilience to the global health threat from already unavoidable climate change is real and urgent. Action must not be delayed by contrarians, nor by catastrophic fatalists who say it is all too late.


Association between C-reactive protein and risk of schizophrenia: An updated meta-analysis.
C-reactive protein (CRP) has been indicated to be associated with the pathogenesis of schizophrenia (SZ) and other psychiatric disorders. The aim of this study is to investigate whether peripheral blood CRP levels are associated with the risk of SZ. We searched literature from databases of Pubmed, Embase and the Cochrane Library from inception to November 1, 2016 for studies that reported serum or plasma CRP levels in patients with SZ and non-SZ controls. At least two reviewers decided on eligibility and extracted data from included studies. Random effects meta-analyses were performed using standardized mean difference (SMD) as the effect estimate of the differences in CRP levels between subjects with SZ and healthy controls. We identified 18 studies representing 1963 patients with SZ and 3683 non-SZ controls. Compared with non-schizophrenics, blood CRP levels were moderately increased in people with SZ (SMD 0.53, 95% CI 0.30 to 0.76) irrespective of study region, sample size of included studies, patient mean age, age of SZ onset and patient body mass index. Publication bias was not detected through Egger's linear regression test (P = 0.292). We noticed that patients in Asia or Africa (n = 6, SMD 0.73, 95% CI 0.26 to 1.21) and whose age less than 30 years (n = 5, SMD 0.76, 95% CI 0.07 to 1.58) had substantially higher CRP levels. Our study provides evidence that higher CRP levels are associated with increased risk of SZ, especially for young adult patients less than 30 years. Further large-scale studies are strongly warranted to further confirm this association.


Anti-Inflammatory Effects of Hyperbaric Oxygenation during DSS-Induced Colitis in BALB/c Mice Include Changes in Gene Expression of HIF-1α, Proinflammatory Cytokines, and Antioxidative Enzymes.
Reactive oxygen species (ROS) and nitrogen species have an indispensable role in regulating cell signalling pathways, including transcriptional control via hypoxia inducible factor-1α (HIF-1α). Hyperbaric oxygenation treatment (HBO2) increases tissue oxygen content and leads to enhanced ROS production. In the present study DSS-induced colitis has been employed in BALB/c mice as an experimental model of gut mucosa inflammation to investigate the effects of HBO2 on HIF-1α, antioxidative enzyme, and proinflammatory cytokine genes during the colonic inflammation. Here we report that HBO2 significantly reduces severity of DSS-induced colitis, as evidenced by the clinical features, histological assessment, impaired immune cell expansion and mobilization, and reversal of IL-1β, IL-2, and IL-6 gene expression. Gene expression and antioxidative enzyme activity were changed by the HBO2 and the inflammatory microenvironment in the gut mucosa. Strong correlation of HIF-1α mRNA level to GPx1, SOD1, and IL-6 mRNA expression suggests involvement of HIF-1α in transcriptional regulation of these genes during colonic inflammation and HBO2. This is further confirmed by a strong correlation of HIF-1α with known target genes VEGF and PGK1. Results demonstrate that HBO2 has an anti-inflammatory effect in DSS-induced colitis in mice, and this effect is at least partly dependent on expression of HIF-1α and antioxidative genes.


Why Temporal Inference Stimulation May Fail in the Human Brain: A Pilot Research Study.
Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal.


A Rare Presentation of Concomitant Lung Disease and Hepatitis After Rituximab Treatment: A Case Report.
Rituximab (RTX) is a chimeric monoclonal antibody that is a standard component of treatment for all B-cell malignancies. The most common adverse events related to RTX are infusion-related reactions, such as fever, chills, urticaria, flushing, and headaches. However, RTX-induced lung disease (RTX-ILD) is a rare but potentially fatal adverse reaction, and diagnosing RTX-ILD is challenging, especially when accompanied by other rare adverse reactions, such as hepatitis. Here, we report a case of RTX-ILD with concomitant RTX-induced hepatitis in a 55-year-old man with follicular B-cell non-Hodgkin lymphoma who was on maintenance RTX therapy. The patient presented with a subacute, persistent dry cough, shortness of breath, fevers, and chills shortly after having traveled. Outpatient antibiotic therapy did not relieve symptoms, and laboratory studies revealed evidence of liver injury. A computed tomography (CT) of the chest showed predominately basilar airspace disease and ground glass opacities suggestive of multifocal pneumonia. Extensive infectious and autoimmune workups were negative. RTX-ILD with concomitant RTX-induced hepatitis was considered because antibiotic therapy did not resolve symptoms or improve signs of liver damage. Prednisone (1 mg/kg) led to symptom resolution and liver enzyme improvement. The patient underwent a 30-day steroid taper and the withholding of RTX infusions. A CT of the chest three months after discharge showed nearly resolved multifocal ground glass opacities. RTX-ILD should be considered after infectious and autoimmune etiologies have been ruled out for all patients on RTX therapy who experience symptoms of lung pathology or infection.


Evaluation of phenylephrine and exercise with or without trocarization for treatment of suspected nephrosplenic entrapment in horses.
OBJECTIVE To report the outcomes of horses with suspected nephrosplenic entrapment (NSE) of the large colon treated by IV phenylephrine administration and exercise with and without trocarization (ie, medical management). DESIGN Retrospective, observational study. ANIMALS 134 horses. PROCEDURES Electronic medical records were searched to identify horses that underwent medical management for suspected NSE at a veterinary teaching hospital between 1995 and 2014. Demographic information, physical and ultrasonographic examination findings, treatment information (including the number of times the treatment was performed and patient response), surgical findings if applicable, complications, and patient outcome were recorded. Descriptive statistics were reported. RESULTS 72 horses had suspected NSE that resolved with medical treatment; 59 of 62 horses underwent laparotomy when medical management failed, and 3 were euthanized without surgery. Twenty-five of the 59 horses had confirmed NSE that was surgically corrected, and 34 had lesions other than or in addition to NSE. All horses that had surgically corrected NSE and 18 of 34 horses that had other lesions survived to hospital discharge. The odds of resolution of NSE with medical management were greater for horses that underwent ≤ 2 (vs > 2) treatments. The treatment success rate for horses that underwent trocarization was not greater than that for horses that did not have the procedure. CONCLUSIONS AND CLINICAL RELEVANCE Suspected NSE resolved with the described medical management for most horses. However, results indicated the potential for misdiagnosis was high. Timely surgical intervention is recommended for horses that fail to respond to medical treatment.


The microbiology of tonsils in khamis civil hospital, saudi arabia.
Objectives. Tonsillitis is a common infection in all age groups, especially under the age of five. Organisms causing this condition vary from place to place. Our aim is to find out the main causative agents of this condition in our hospital. Patients and Methods. Fifty-two consenting patients who needed tonsillectomy in Khamis civil hospital, Kingdom of Saudi Arabia, between September 2006 and April 2007, were enrolled for the study. Swabs were taken from their inner surfaces and cultured for anaerobes and aerobes according to standard microbiological techniques. Results. Fifty-two patients, consisting of 30 males and 22 females were enrolled. Their mean age was 9.81 ± 6.47. Nearly 65% of patients had positive cultures while 35% were negative. The commonest bacteria isolated were Staphylococcus aureus (44.1%); and Group B Streptococcus (35.3 %). Two Gram-negative bacteria, Klebsiella pneumoniae, (8.82%), and Pseudomonas aeruginosa (2.94 %), were also isolated. No anaerobe was isolated. Conclusion. Gram-positive cocci, consisting of Staphylococcus aureus and Group B Streptococcus (Streptococcus agalactiae), are the major causes of tonsillitis requiring surgery in our hospital. Antibiotic treatment of this condition should be directed largely against these organisms.


Coarse WDM networking of self-referenced fiber-optic intensity sensors with reconfigurable characteristics.
A CWDM network operating in reflective configuration for multiplexing remote Radio-Frequency (RF) self-referenced fiber-optic intensity sensors is analyzed and experimentally investigated. In the described approach, the use of fiber Bragg gratings as spectral selective mirrors allows to implement delay lines in the electrical domain, achieving more compact sensor-heads and easy-reconfigurable sensing points. Two measurement parameters for the sensing heads are defined and comparatively studied in terms of design parameters, linearity, sensitivity and resolution. The proposed sensor configuration is modeled following the Z-transform formalism, which permits an easy analysis of the system frequency response. Experimental results are presented, showing the characterization of the network performance and considering the properties of sensor self-referencing as well as sensor crosstalk.


A phase I clinical and pharmacokinetic study of fenretinide combined with paclitaxel and cisplatin for refractory solid tumors.
Fenretinide is a semi-synthetic retinoid that has pro-apoptotic effects as a single agent and synergistically with chemotherapy in vitro. We performed this study to determine the toxicity of cisplatin, paclitaxel and fenretinide in patients with advanced cancer, the recommended phase II dose of these agents together, and the pharmacokinetics (PK) of fenretinide when administered with chemotherapy. Fourteen patients (mean age 57.3) were assessable for pharmacokinetics, toxicity and response. Fenretinide was given orally in 2 divided daily doses for 7 days, starting 24 hours prior to cisplatin and paclitaxel. Cisplatin and paclitaxel were given in standard fashion. Cycles were repeated every 3 weeks. Cycle one fenretinide PK was obtained on days 2 and 8. Dose limiting toxicity (Gr 3 diarrhea and Gr 4 neutropenia) was encountered in two patients during cycle one at 80/175/1,800 mg/m(2) of cisplatin/paclitaxel/fenretinide (dose level 2), respectively. Seven patients received 2-8 cycles at the recommended level of 60/135/1,800 (dose level 1). Severe cumulative toxicities included fatigue, nausea/vomiting, neuropathy, and dehydration. Two patients had a partial response and 4 patients had stable disease for up to 8 cycles. PK analysis demonstrated a reduction in fenretinide Cmax on day 8 compared to day 2, accompanying a decrease in AUC. Cisplatin/paclitaxel/fenretinide can be administered safely at 60/135/1,800 mg/m(2) respectively on an every three-week schedule. This combination may have activity in a variety of tumors, however, the number of pills required complicates oral dosing of fenretinide, and limits the applicability of this regimen.


Spinal nerve lesion induces upregulation of constitutive isoform of heme oxygenase in the spinal cord. An immunohistochemical investigation in the rat.
The influence of carbon monoxide (CO) on chronic spinal nerve lesion induced spinal cord neurodegeneration was examined using immunohistochemical expression of the constitutive isoform of its synthesising enzyme, hemeoxygenase-2 (HO-2) in a rat model. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model of neuropathic pain and rats were allowed to survive for 8 weeks. Sham operated rats, in which the spinal nerves were exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of HO-2 expression which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, morphological investigations showed distorted neurons, membrane disruption, synaptic damage and myelin vesiculation. Sham operated rats did not show an upregulation of HO-2 expression and the structural changes in the spinal cord were absent. These observations strongly suggest that spinal nerve lesion is associated with an increased production of CO which is somehow contributing to the neurodegenerative changes in the spinal cord, not reported earlier.


Prevalence and Mortality Rate of Sepsis among Adults admitted to Hospitals in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.
Due to abundant pathogen diversity and mounting antimicrobial resistance, sepsis is more common in sub-Saharan Africa (sSA). However, there is a lack of consistent reports regarding the prevalence of adult sepsis in the region. Therefore, this study aimed to determine pooled estimates of sepsis prevalence and associated mortality among adults admitted to hospitals in sSA. Medline (through PubMed), Scopus, Embase, and Web of Science were systematically searched for studies of sepsis in sSA published before February 13, 2023. A random-effects meta-analysis of hospital-wide and intensive care unit (ICU)-based sepsis prevalence was performed with a 95% confidence interval (CI). Subgroup analysis was conducted considering geographic region and sepsis diagnostic criteria. Funnel plots and Egger's test were used to assess publication bias. The protocol was submitted to the Prospective Register for Systematic Reviews (PROSPERO) with an identifier (CRD42023396719). Overall, 14 observational studies, published between 2009 and 2022, from eight different sSA countries comprising 31,653 adult patients (5,723 with sepsis) were included in the review. Nine studies that were conducted in a hospital-wide setting showed a pooled prevalence and mortality of 17% (95% CI: 12-21%) and 15% (95% CI: 17-35%), respectively. Five studies in the ICUs presented a pooled prevalence and mortality of 31% (95% CI: 24-38%) and 46% (95% CI: 39-54%), respectively. Based on the sub-group analysis, the pooled hospital-wide prevalence of sepsis in East and Southern Africa was 18% (95% CI: 11-25%), and 20% (95% CI: 2-42%), respectively. The pooled prevalence in the ICU was 14% (95% CI: 4-23%) and 13% (95% CI: 5-20%) for East and Southern Africa, respectively. The hospital-wide and ICU-based sepsis prevalence and mortality are high in sSA. Addressing the burden of adult sepsis should be a priority for healthcare systems in sub-Saharan Africa.


[Pharmacological approaches to study of choline- and GABA-receptor sta tes in neuronal membranes after low doses irradiation].
As a result of the study of both the acetylcholine (10(-10) M; 10(-6) M) and gamma-aminobutyric acid (10(-9) M; 10(-5) M) effects on active K+ transport in rat brain cortex slices using any selective antagonists of cholinoreceptors (ChR) and GABA-receptors (GABA-R) it had been shown that after whole-body 25 cGy irradiation (1.75 mGy/min) metabotropic muscarinic ChR and GABAB-R were involved into processes of neurotransmitter modulation, whereas under the normal conditions they were mediated via ionotropic nicotinic ChR and GABAA-R. Observed changes were supposed to be an adaptive reaction. Perhaps, postirradiation structure-functional disorders in receptors were pointed as one of the reasons leading to essential changes in the interneuronal metabolic communication processes in CNS.


Factors related to depression during menopause: a study in southern Taiwan.
The purpose of this study was to survey the prevalence of women's depression during menopause and investigate the relationships between menopause depression and variables including self-concept, menopause attitudes, life-event stresses, climacteric physiological symptoms, and demographics. Research was conducted using a cross-sectional study and self-administered questionnaires. We randomly selected female participants between the ages of 45 and 55 years from Tainan City in southern Taiwan using the cluster method. Two hundred sixty-six valid questionnaires were analyzed. Results were as follows: (a) The prevalence of depression among participants was 31.2%; (b) depression was positively associated with life-event stresses and climacteric physiological symptoms (r =.23 and .34, respectively) and was negatively associated with attitude toward menopause and self-concept (r = -.31 and -.65, respectively); and (c) by logistic regression analyses, climacteric physiological symptoms and self-concept were associated with menopause depression. This preliminary survey suggests that low self-concept and increased climacteric physiological symptoms are closely related to depression among menopausal women. Larger scale follow-up studies are warranted to investigate factors that predispose women to depression during menopause.


Molecular characterization of encephalomyocarditis virus strains isolated from an African elephant and rats in a French zoo.
In November 2013, a fatal encephalomyocarditis virus (EMCV) case in a captive African elephant (Loxodonta africana) occurred at the Réserve Africaine de Sigean, a zoo in the south of France. Here we report the molecular characterization of the EMCV strains isolated from samples collected from the dead elephant and from 3 rats (Rattus rattus) captured in the zoo at the same time. The EMCV infection was confirmed by reverse-transcription real-time PCR (RT-rtPCR) and genome sequencing. Complete genome sequencing and sequence alignment indicated that the elephant's EMCV strain was 98.1-99.9% identical to the rat EMCV isolates at the nucleotide sequence level. Phylogenetic analysis of the ORF, P1, VP1, and 3D sequences revealed that the elephant and rat strains clustered into lineage A of the EMCV 1 group. To our knowledge, molecular characterization of EMCV in France and Europe has not been reported previously in a captive elephant. The full genome analyses of EMCV isolated from an elephant and rats in the same outbreak emphasizes the role of rodents in EMCV introduction and circulation in zoos.


Endothelial PAS domain protein 1 gene hypomethylation is associated with colorectal cancer in Han Chinese.
Endothelial PAS domain-containing protein 1 (EPAS1) serves a role in angiogenesis, which is important for the development of tumors, including colorectal cancer (CRC). The current study aimed to estimate whether EPAS1 methylation was associated with CRC. A two-stage association study of EPAS1 methylation and CRC was conducted. In the first phase, EPAS1 methylation was evaluated in the tumor and adjacent non-tumor tissue samples from 41 patients with sporadic CRC in Jiangsu province, China. The diagnostic value of methylation of EPAS1 for CRC in the second phase was evaluated in 79 patients with sporadic CRC and 22 normal individuals in Zhejiang province, China. The methylation assay was performed using a quantitative methylation-specific polymerase chain reaction (qMSP) method. The percentage of methylated reference (PMR) was used to quantify the methylation level. The first-stage results indicated that EPAS1 promoter methylation was significantly lower in CRC tumor tissues compared with 5-cm-para-tumor tissues (median PMR, 0.59 vs. 1.22%; P=0.027) and 10-cm-para-tumor tissues (median PMR, 0.59 vs. 1.89%; P=0.001). In addition, the second-stage results indicated that EPAS1 promoter methylation was significantly lower in tumor tissues compared with 5-cm-para-tumor tissues (median PMR, 1.91 vs. 6.25%; P=3×10-7) and normal intestinal tissues from healthy controls (median PMR, 1.91 vs. 28.4%; P=5×10-7). Receiver Operating Characteristic curve analysis of the second-stage data indicated that the highest area under the curve of EPAS1 hypomethylation was 0.851 between Zhejiang CRC tissues and Zhejiang normal intestinal tissues (sensitivity, 95.5%; specificity, 60.8%).


X-ray structure of an unusual Ca2+ site and the roles of Zn2+ and Ca2+ in the assembly, stability, and storage of the insulin hexamer.
Metal ion binding to the insulin hexamer has been investigated by crystallographic analysis. Cadmium, lead, and metal-free hexamers have been refined to R values of 0.181, 0.172, and 0.172, against data of 1.9-, 2.5-, and 2.5-A resolution, respectively. These structures have been compared with each other and with the isomorphous two-zinc insulin. The structure of the metal-free hexamer shows that the His(B10) imidazole rings are arranged in a preformed site that binds a water molecule and is poised for Zn2+ coordination. The structure of the cadmium derivative shows that the binding of Cd2+ at the center of the hexamer is unusual. There are three symmetry-related sites located within 2.7 A of each other, and this position is evidently one-third occupied. It is also shown that the coordinating B13 glutamate side chains of this derivative have two partially occupied conformations. One of these conformations is two-thirds occupied and is very similar to that seen in two-zinc insulin. The other, one-third-occupied conformation, is seen to coordinate the one-third-occupied metal ion. The binding of Ca2+ to insulin is assumed to be essentially identical with that of Cd2+. Thus, we conclude that the Ca2+ binding site in the insulin hexamer is unlike that of any other known calcium binding protein. The crystal structures reported herein explain how binding of metal ions stabilizes the insulin hexamer. The role of metal ions in hexamer assembly and dissociation is discussed.


Comparison of Spatial Modelling Approaches on PM10 and NO2 Concentration Variations: A Case Study in Surabaya City, Indonesia.
Because of fast-paced industrialization, urbanization, and population growth in Indonesia, there are serious health issues in the country resulting from air pollution. This study uses geospatial modelling technologies, namely land-use regression (LUR), geographically weighted regression (GWR), and geographic and temporal weighted regression (GTWR) models, to assess variations in particulate matter (PM10) and nitrogen dioxide (NO2) concentrations in Surabaya City, Indonesia. This is the first study to implement spatiotemporal variability of air pollution concentrations in Surabaya City, Indonesia. To develop the prediction models, air pollution data collected from seven monitoring stations from 2010 to 2018 were used as dependent variables, while land-use/land cover allocations within a 250 m to 5000 m circular buffer range surrounding the monitoring stations were collected as independent variables. A supervised stepwise variable selection procedure was applied to identify the important predictor variables for developing the LUR, GWR, and GTWR models. The developed models of LUR, GWR, and GTWR accounted for 49%, 50%, and 51% of PM10 variations and 46%, 47%, and 48% of NO2 variations, respectively. The GTWR model performed better (R2 = 0.51 for PM10 and 0.48 for NO2) than the other two models (R2 = 0.49-0.50 for PM10 and 0.46-0.47 for NO2), LUR and GWR. In the PM10 model four predictor variables, public facility, industry and warehousing, paddy field, and normalized difference vegetation index (NDVI), were selected during the variable selection procedure. Meanwhile, paddy field, residential area, rainfall, and temperature played important roles in explaining NO2 variations. Because of biomass burning issues in South Asia, the paddy field, which has a positive correlation with PM10 and NO2, was selected as a predictor. By using long-term monitoring data to establish prediction models, this model may better depict PM10 and NO2 concentration variations within areas across Asia.


Alveolar macrophage modulation via the gut-lung axis in lung diseases.
Several studies have demonstrated great potential implications for the gut-lung axis in lung disease etiology and treatment. The gut environment can be influenced by diet, metabolites, microbiotal composition, primary diseases, and medical interventions. These changes modulate the functions of alveolar macrophages (AMs) to shape the pulmonary immune response, which greatly impacts lung health. The immune modulation of AMs is implicated in the pathogenesis of various lung diseases. However, the mechanism of the gut-lung axis in lung diseases has not yet been determined. This mini-review aimed to shed light on the critical nature of communication between the gut and AMs during the development of pulmonary infection, injury, allergy, and malignancy. A better understanding of their crosstalk may provide new insights into future therapeutic strategies targeting the gut-AM interaction.


Pitfalls in the Cytological Assessment of Thyroid Nodules.
Fine needle aspiration of thyroid has been used for years in a multidisciplinary approach, to diagnose different entities, in preventing over or under treatment of thyroid nodules. The widespread use of this methodology can be confirmed if "thyroid fine needle aspiration" is searched on PubMed, which results in over 5000 papers. In this manuscript, we aimed to focus on pitfalls in the evaluation of thyroid aspirations, covering cystic, inflammatory lesions, follicular lesions, oncocytic lesions, papillary carcinoma, and medullary carcinoma of thyroid.


Sleep and endocrine regulation.
A bidirectional interaction exists between sleep electroencephalogram (EEG) and endocrine activity in various species including humans. Various hormones (peptides, steroids) were shown to participate in sleep regulation. A keyrole was shown for the reciprocal interaction between sleep-promoting growth hormone-releasing hormone (GHRH) and sleep-impairing corticotropin-releasing hormone (CRH). Changes in the GHRH:CRH ratio result in changes of sleep-endocrine activity. There is good evidence that the change of this ratio in favor of CRH contributes to aberrances of sleep during aging and depression. Besides of GHRH ghrelin and galanin promote SWS, whereas somatostatin is another sleep-impairing factor. NPY acts as a CRH antagonist and induces sleep onset. Prolactin enhances rapid eve-movement sleep (REMS) in rats. SWS is enhanced in patients with prolactinoma. Other studies on the influence of prolactin of human sleep are lacking. There is a controversy whether CRH promotes REMS. In humans vasocactive intestinal polypeptide (VIP) appears to play a role in the temporal organization of sleep, since after VIP administration the NREMS-REMS cycle decelerated. Several neuroactive steroids (pregnenolone, progesterone, allopregnanolone, dehydroepiandrosterone) exert specific effects on sleep EEG via GABAA receptors. Cortisol appears to enhance REMS. Finally gonadal hormones participate in sleep regulation. Estrogen replacement therapy and CRH-1 receptor antagonism in depression are beneficial clinical applications of the basic research presented here.


An mHealth-Based Intervention for Adolescents With Type 1 Diabetes and Their Parents: Pilot Feasibility and Efficacy Single-Arm Study.
Type 1 diabetes (T1D) affects more than 165,000 individuals younger than 20 years in the United States of America. The transition from parent management to parent-child team management, with the child taking on increased levels of self-care, can be stressful and is associated with a deterioration in self-management behaviors. Therefore, a mobile app intervention, MyT1DHero, was designed to facilitate diabetes-specific positive parent-adolescent communication and improve diabetes-related outcomes. The MyT1DHero intervention links an adolescent with T1D and their parent through 2 separate app interfaces and is designed to promote positive communication regarding T1D management. The aim of this pilot study was to determine (1) the initial efficacy of the MyT1DHero intervention in improving diabetes outcomes in adolescents, specifically the hemoglobin A1c (HbA1c) levels, diabetes care adherence, and quality of life, and (2) the adolescents' overall satisfaction with this intervention. This pilot study included 30 adolescent-parent pairs who used the MyT1DHero app in a 12-week single-arm clinical trial. Participants were recruited from the local pediatric endocrinology subspecialty clinic via snowball sampling. HbA1c levels, diabetes care adherence, quality of life, family conflict, and satisfaction levels were measured and analyzed using paired sample two-sided t tests and linear regression analyses. The final analysis included 25 families. The mean age of the adolescents was 12.28 (SD 1.62) years. Half of the participants (13/25) reported a diabetes diagnosis of less than 5 years. After 12 weeks of the intervention, diabetes care adherence significantly improved (before the study: mean 3.87 [SD 0.59]; after the study: mean 4.19 [SD 0.65]; t21=-2.52, P=.02, d=0.52) as did quality of life (before the study: mean 4.02 [SD 0.84]; after the study: mean 4.27 [SD 0.73]; t24=2.48, P=.01, d=0.32). HbA1c levels (before the study: mean 8.94 [SD 1.46]; after the study: mean 8.87 [SD 1.29]; t24=0.67, P=.51, d=0.04) and family conflict (before the study: mean 2.45 [SD 0.55]; after the study: mean 2.61 [SD 0.45]; t23=0.55, P=.14, d=0.32) changed in the hypothesized direction, but the change was not significant. However, higher use of the mobile app was associated with more improvement in HbA1c levels (F1,20=9.74, P<.005; R2=0.33). Overall, the adolescents were satisfied with the app intervention. In a 12-week pilot study of the mobile app intervention designed to facilitate parent-adolescent communication for improving diabetes outcomes, significant benefits were demonstrated in self-care adherence and quality of life. A randomized controlled trial with a longer intervention is needed to replicate these findings and to determine the stability of the intervention effects. ClinicalTrials.gov NCT03436628; https://clinicaltrials.gov/ct2/show/NCT03436628.


Leucine-rich repeat kinase-2 (LRRK2) modulates paraquat-induced inflammatory sickness and stress phenotype.
Leucine-rich repeat kinase 2 (LRRK2) is a common gene implicated in Parkinson's disease (PD) and is also thought to be fundamentally involved in numerous immune functions. Thus, we assessed the role of LRRK2 in the context of the effects of the environmental toxicant, paraquat, that has been implicated in PD and is known to affect inflammatory processes. Male LRRK2 knockout (KO) and transgenic mice bearing the G2019S LRRK2 mutation (aged 6-8 months) or their littermate controls were exposed to paraquat (two times per week for 3 weeks), and sickness measures, motivational scores, and total home-cage activity levels were assessed. Following sacrifice, western blot and ELISA assays were performed to see whether or not LRRK2 expression would alter processes related to plasticity, immune response processes, or the stress response. Paraquat-induced signs of sickness, inflammation (elevated IL-6), and peripheral toxicity (e.g., organ weight) were completely prevented by LRRK2 knockout. In fact, LRRK2 knockout dramatically reduced not only signs of illness, but also the motivational (nest building) and home-cage activity deficits induced by paraquat. Although LRRK2 deficiency did not affect the striatal BDNF reduction that was provoked by paraquat, it did blunt the corticosterone elevation induced by paraquat, raising the possibility that LRRK2 may modulate aspects of the HPA stress axis. Accordingly, we found that transgenic mice bearing the G2019S LRRK2 mutation had elevated basal corticosterone, along with diminished hippocampal 5-HT1A levels. We are the first to show the importance of LRRK2 in the peripheral neurotoxic and stressor-like effects of paraquat. These data are consistent with LRRK2 playing a role in the general inflammatory tone and stressor effects induced by environmental toxicant exposure.


Mixture genotoxicity of 2,4-dichlorophenoxyacetic acid, acrylamide, and maleic hydrazide on human Caco-2 cells assessed with comet assay.
Assessment of genotoxic properties of chemicals is mainly conducted only for single chemicals, without taking mixture genotoxic effects into consideration. The current study assessed mixture effects of the three known genotoxic chemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), acrylamide (AA), and maleic hydrazide (MH), in an experiment with a fixed ratio design setup. The genotoxic effects were assessed with the single-cell gel electrophoresis assay (comet assay) for both single chemicals and the ternary mixture. The concentration ranges used were 0-1.4, 0-20, and 0-37.7 mM for 2,4-D, AA, and MH, respectively. Mixture toxicity was tested with a fixed ratio design at a 10:23:77% ratio for 2.4-D:AA:MH. Results indicated that the three chemicals yielded a synergistic mixture effect. It is not clear which mechanisms are responsible for this interaction. A few possible interactions are discussed, but further investigations including in vivo studies are needed to clarify how important these more-than-additive effects are for risk assessment.


[Hemodynamic mechanisms of the functioning of axillofemoral shunts].
Central and regional hemodynamic parameters were investigated in experimental models of axillofemoral shunts, using electromagnetic flowmetry and electromanometry. Shunt function was shown to be based exclusively on the regional hemodynamic mechanism where blood is "borrowed" from brachycephalic branches of the arch of the aorta. Conditions were identified that contributed to the "stealing" phenomenon in the presence of axillofemoral shunting.


Lipid filling and lipolysis in adipose tissue and cells.
Fatty acids are transported from circulating blood lipoproteins to adipocytes during lipid filling of adipose tissue and from adipocytes to the capillary lumen during lipid mobilization. Our studies with chylomicrons and lipid monolayers show that ampipathic fatty acids formed by the action of lipoprotein lipase locate and move in the interface between lipid and the aqueous phase. Our studies on brown and white adipose tissue show that fatty acids formed by the action of lipoprotein lipase on chylomicrons at the capillary endothelial surface and by the action of hormone sensitive lipase on intracellular lipid droplets locate in an interfacial continuum composed of the outer leaflets of the plasma membrane of cells and the lumenal leaflets of intracellular membranes. Ampipathic fatty acids can be visualized with electron microscopy as lamellar structures. In fixed tissue fatty acids which overcrowd the interfacial continuum form lamellar extensions of the external leaflet of membranes at different sites along their transport route. In adipose tissue of fed animals lamellar structures extend from chylomicrons at the capillary endothelial surface through trans-endothelial channels to adipocytes marking the route of transport of fatty acids during lipid filling of adipose tissue. In adipose tissue of fasted animals lamellar structures extend from intracellular lipid droplets through intracellular channels to the plasma membrane of adipocytes marking the route of fatty acid transport during lipid mobilization. In adipocytes from brown adipose tissue of cold-stressed young animals lamellar structures extend from intracellular lipid droplets to the outer mitochondrial chamber marking the route of transport of fatty acids to mitochondria for oxidation and heat production.


The effect of educational program on knowledge, attitude and practice of mothers regarding prevention of febrile seizure in children.
Febrile convulsion is one of the most common problems in children aged 5 months to 6 years. The aim of this study was to explore the effectiveness of an educational program on mothers for prevention of febrile seizure in children. In this clinical trial study, 88 mothers were chosen who were divided into intervention and control groups, randomly. Data of the control and intervention groups were collected in two stages, before intervention and 1 month after intervention, by a validated and reliable questionnaire. The intervention consisted of three educational sessions, each one lasting for 60 min. Data were analyzed using chi-square, t-test and paired t-test. Age average of subjects in the intervention group and in the control group was 26.75 and 26.84 years, respectively. The results showed a significant increase in the knowledge (P < 0.001), attitude (P = 0.04) and practice (P = 0.01) in the intervention group 1 month after intervention compared with that before intervention, while such an increase was not seen in the control group. This study confirmed the efficiency of educational interventions in improving mother's knowledge, attitude and practice regarding prevention of febrile seizure in children.