ZrO2@chitosan composite for simultaneous photodegradation of three emerging contaminants and antibacterial application.
Emerging contaminants (ECs) are often detected in water bodies due to their prevalent use combined with inefficiency of the conventional wastewater treatment plants for their complete removal. Elimination of ECs using photocatalysis as a tertiary treatment can be a sustainable option for the reuse wastewater. Reported herewith is a photocatalyst, chitosan-based zirconia hybrid composite (ZrO2CTS-HC) for the individual/ simultaneous degradation of multiple ECs like Congo red (CR), Methyl orange (MO) and 4-hydroxybenzoic acid (4-HA) under visible light irradiation. Successfully synthesized ZrO2CTS-HC as confirmed by theoretical and various characterization techniques depicted photodegradation efficiency of 91.11, 69.11 and 78.40% for CR, MO and 4-HA respectively (SD 0.5-0.95; HPLC) aided by the reactive hydroxyl radical. Probable degradation mechanism supported by LC-MS/MS, COD and TOC along with reusability and antibacterial ability towards E.Coli & S.aureus is also reported. ZrO2CTS-HC can be a good option for elimination of residual ECs during tertiary treatment.


Choroidal neovascularization after laser-assisted in situ keratomileusis following penetrating keratoplasty.
To describe a case of choroidal neovascularization (CNV) after laser in situ keratomileusis (LASIK) following penetrating keratoplasty (PK). Case report. A 30-year-old man underwent PK in both eyes for bilateral keratoconus in 1997. Two years later, best-corrected visual acuity (BCVA) was 20/40 (-6=-4.50 x 170 degrees ) in RE and 20/20 (-1.50=-0.50 x 90 degrees ) in LE. To reduce the anisometropic defect, LASIK was performed in RE. After surgery, the refractive defect in RE reduced to -1.75 x 125 degrees and BCVA improved to 20/25. Six months after LASIK the patient presented loss of vision and metamorphopsia in RE due to choroidal neovascularization. BCVA was reduced to 20/200. Photodynamic therapy was performed in RE; 1 year later BCVA was stable at 20/200. Vitreoretinal complications after LASIK occur rarely. The potential relationship between CNV and LASIK is discussed.


Activation of the human transforming growth factor alpha (TGF-alpha) gene by the hepatitis B viral X protein (HBx) through AP-2 sites.
The HBx protein is known as a transactivator and potential oncogene, and TGF-alpha as a potent mitogen in hepatocellular carcinoma. By assays of serial deletion of the promoter of TGF-alpha gene and the cotransfection of HBx and AP-2 expression vectors, we observed that the HBx significantly activated the promoter activity through AP-2 sites located in the proximal region of the TGF-alpha promoter (-136 to -30). This effect was also observed in the heterologous promoter assay system containing AP-2 sites. The mutation analyses of three AP-2 sites in the promoter revealed that all three AP-2 sites contributed to the activation of the TGF-a gene in the presence of HBx. Accordingly, the mRNA level of TGF-alpha was significantly elevated in the HBx-expressing cell, HepG2-HBx and the HBV-producing cell, HepG2-K8. These results suggest that the HBx protein could increase the mitogenic effect of TGF-alpha by the transactivation of the gene through AP-2 binding sites and consequently, these interactions may accelerate the process of hepatocarcinogenesis.


Treatment stratification and prognosis assessment using circulating tumor DNA in locally advanced rectal cancer: A systematic review and meta-analysis.
Circulating tumor DNA (ctDNA) is an emerging biomarker for locally advanced rectal cancer (LARC), giving hope for stratified treatment. As the completed studies have small sample sizes and different experimental methods, systematic review and meta-analysis were performed to explore their role in predicting pathological complete response (pCR), tumor recurrence, and prognosis. PubMed, Embase, and the Web of Science were searched for potentially eligible studies published up to September 6, 2022. Pooled relative risk (RR) was calculated to predict pCR and tumor recurrence, and pooled hazard ratio (HR) was calculated to evaluate the prognosis of overall survival (OS), recurrence-free survival (RFS), and metastasis-free survival (MRS). Twelve studies published between 2018 and 2022 included 931 patients, and 2544 serum samples were eventually included in the meta-analysis. The pooled revealed that ctDNA-negative patients were more likely to have a pCR (RR = 1.64, 95% confidence interval [CI]: 1.26-2.12). The pooled revealed that ctDNA-positive patients were at high risk of recurrence (RR = 3.37, 95% CI: 2.34-4.85) and had a poorer prognosis for OS (HR = 3.03, 95% CI: 1.86-4.95), RFS (HR = 7.08, 95% CI: 4.12-12.14), and MRS (HR = 2.77, 95% CI: 2.01-3.83). ctDNA may be useful for stratifying treatment and assessing prognosis in patients with LARC, but its clinical application still needs to be confirmed in a prospective multicenter study with large samples.


Clinicopathological significance and prognostic value of the expression of the cancer stem cell marker CD133 in hepatocellular carcinoma: a meta-analysis.
To conduct a meta-analysis to assess the association between CD133 expression and clinicopathological significance and prognostic value in hepatocellular carcinoma patients. Studies were identified via an electronic comprehensive literature search through the Pubmed, Chinese CNKI, and Wanfang databases. This meta-analysis was performed using Stata statistical software version 12.0. The outcomes included various clinicopathological and survival parameters (P < 0.05 was consider to indicate a statistical significance). A total of 21 studies comprising 2592 patients were included in this meta-analysis. CD133 overexpression was significantly associated with a series of clinicopathological parameters, such as low tumor differentiation (pooled odds ratio (OR) = 2.26, 95% CI: 1.59-3.21, P < 0.00001), advanced tumor stage (pooled OR = 2.17, 95% CI: 1.70-2.77, P < 0.00001), vascular invasion (pooled OR = 2.06, 95% CI: 1.25-3.39, P = 0.005), and vascular thrombosis (pooled OR = 1.47, 95% CI: 1.08-1.99, P = 0.015). However, CD133 expression was not correlated with hepatitis, cirrhosis, α-fetoprotein level, tumor number, tumor size, encapsulation, or metastasis. Regarding survival outcome, CD133 overexpression was significantly correlated with poor overall survival (pooled hazard ratio (HR) = 2.01, 95% CI: 1.45-2.80, P = 0.00002) and poor disease-free survival (pooled HR = 1.82, 95% CI: 1.45-2.29, P < 0.00001). This meta-analysis indicated that CD133 overexpression is significantly associated with clinicopathological factors and poorer survival outcome.


Models of glycoprotein hormone receptor interaction.
The glycoprotein hormones regulate reproduction and development through their interactions with receptors in ovarian, testicular, and thyroid tissues. Efforts to design hormone agonists and antagonists useful for treat-ing infertility and hyperthyroidism would benefit from a molecular understanding of hormone-receptor interaction. The structure of a complex containing FSH bound to a fragment of its receptor has been determined at 2.9 Angstroms resolution, but this does not explain several observations made with cell-surface G protein receptors and may reflect the manner in which FSH binds a short alternate spliced receptor form. We discuss observations that must be explained by any model of the cell-surface G protein-coupled glycoprotein hormone receptors and suggest structures for these receptors that satisfy these requirements. Glycoprotein hormones appear to contact two distinct sites in the extracellular domains of their receptors, not just the leucine-rich repeat domain. These dual contacts contribute to ligand binding specificity and appear to be essential for signal transduction. As outlined in this minireview, differences in the manners in which these ligands contact their receptors explain why some ligands and ligand analogs interact with more than one class of receptor and why some receptors and receptor analogs bind more than one ligand. The unique manner in which these ligands appear to interact with their receptors may have facilitated hormone and receptor co-evolution during early vertebrate speciation.


Xylem water flow in a crack willow tree (Salix fragilis L.) in relation to diurnal changes of environment.
The diurnal course of the xylem water flow in a solitary Salix fragilis L. tree in a wet grassland was measured using the tissue heat-balance method. There was considerable variation due to meteorological factors. Maximum flow rate was 0.4 kg h-1 m-2 of crown projection area, or 5.9 kg h-1 kg-1 leaf dry weight. The daily total was 2.4 kg m-2 day-1 or 36 kg kg-1 day-1. Water flow decreased immediately at the tree base and at the branches after start of rain, and in a branch, after cutting it off: the time constant of the system was 600-700 s in both cases. The part of the crown oriented to the sun transpired up to ten times as much as the shaded part. Over 70% of the total cross-sectional area of the conductive xylem vessels of the trunk was used by the transpiration flow. The water content of the trunk tracked the diurnal changes of the xylem water flow rate with a short time-lag. During the day, 1% of the trunk volume was temporarily exploited as water reserve, an amount equalling 3% of daily water loss. The stereometric configuration of the crown significantly influenced its water loss. During the summer period, about 33 mature (polycormic) trees per ha may drain 100% of water consumed by the present-day sedge-grass marsh.


Activation of SIRT-1 Signalling in the Prevention of Bipolar Disorder and Related Neurocomplications: Target Activators and Influences on Neurological Dysfunctions.
SIRT-1 (silent mating-type information regulation 2 homolog-1) is a protein found in neuronal nuclei, microglia, and astrocyte cells of the brain. It is sometimes referred to as NAD + -dependent deacetylase (nicotinamide adenine dinucleotide). The activation of sirtuins (SIRT-1-7) has been shown to protect against a wide range of disorders, including neurodegenerative and neuropsychiatric disorders. SIRT-1 has gained considerable interest from these families because of its early link to long-life expansion and calorie restriction involvement. SIRT-1 is necessary for gene silencing, cell cycle regulation, fat and glucose metabolism, oxidative stress, ageing, and memory formation. In this review, we investigate the role of SIRT-1 downregulation in the progression of bipolar disorder (BD) and neurological abnormalities, as well as related neurological alterations such as genetic dysfunction, neurotransmitter imbalance, oxidative stress-induced apoptosis, and mitochondrial dysfunction. BD is a psychiatric disease distinguished by extreme mood fluctuations that range from depressive lows to manic highs. BD is a complicated disorder with numerous clinical signs and neurocomplications that produce significant behavioural problems. SIRT-1 deficiency in the brain has been demonstrated to affect the activity of its transcription factors and molecular changes, including genetic defects. SIRT-1 is now being studied as a potential therapeutic target for a range of brain disorders. A recent study also found that activating SIRT-1 signalling performs a protective effect in avoiding depression and mania-like behaviours. Furthermore, this review investigates the potential mechanisms by which SIRT-1 regulates neuronal transmission and neurogenesis. As a result of our review, we revealed that SIRT-1 activators have neuroprotective potential in BD and related neurological dysfunctions.


Intestinal ischemic injury following mild hypothermic stress in the neonatal piglet.
The core body temperature of unanesthetized neonatal piglets was lowered 4 +/- 1 degrees C for 4.5 h. Although systolic blood pressure, arterial blood gases, and pH were similar in hypothermic and control animals, grossly evident small intestinal injury occurred in 94% of hypothermic piglets but in none of the controls (p less than 0.01). The histopathology of the intestinal lesions in the experimental animals was characteristic of ischemic injury and ranged from superficial mucosal necrosis to transmural infarct. The lesions were more frequent in the mid- and distal small bowel and involved the muscularis propria only in the distal small bowel. The location and histopathologic characteristics of the bowel lesions in these animals support the concept that mild hypothermia could be a pathogenetic factor in the ischemic bowel lesions of human neonatal necrotizing enterocolitis.


Intermittent Hypoxia and Diet-Induced Obesity on the Intestinal Wall Morphology in a Murine Model of Sleep Apnea.
This work analyzes the impact of two conditions, intermittent hypoxia exposure and high-fat diet in rats as models of sleep apnea. We studied the autonomic activity and histological structure of the rat jejunum and whether the overlapping of both conditions, as often observed in patients, induces more deleterious effects on the intestinal barrier. We found alterations in jejunum wall histology, predominantly in HF rats, based on increased crypt depth and submucosal thickness, as well as decreased muscularis propria thickness. These alterations were maintained with the IH and HF overlap. An increase in the number and size of goblet cells in the villi and crypts and the infiltration of eosinophils and lymphocytes in the lamina propria suggest an inflammatory status, confirmed by the increase in plasma CRP levels in all experimental groups. Regarding the CAs analysis, IH, alone or combined with HF, causes a preferential accumulation of NE in the catecholaminergic nerve fibers of the jejunum. In contrast, serotonin increases in all three experimental conditions, with the highest level in the HF group. It remains to be elucidated whether the alterations found in the present work could affect the permeability of the intestinal barrier, promoting sleep apnea-induced morbidities.


Common germline MDR1/ABCB1 functional polymorphisms and haplotypes modify susceptibility to colorectal cancers with high microsatellite instability.
Altered expression of P-glycoprotein (P-gp) encoded by the multidrug resistance (MDR1/ABCB1) gene, as well as somatic mutations and hypermethylation in the MDR1/ABCB1 gene, were identified in a proportion of previously untreated colorectal cancers (CRC) exhibiting high microsatellite instability (MSI-H), which suggested that MDR1/ABCB1 acts as a candidate gene contributing to the initiation and progression of MSI-H tumors. Here we report germline functional single nucleotide polymorphisms (SNPs) and haplotypes in the MDR1/ABCB1 gene, which could contribute to genetic risk or increase susceptibility to MSI-H cancers. We have confirmed disease association by comparing the MDR1/ABCB1 genotype, allele, and haplotype frequencies between healthy controls and patients with MSI-H tumors. In particular, carriers of the T/T genotype in exon 12 (1236 C-->T) SNP and the T/T genotype in exon 21 (2677G-->T) SNP were most significantly associated with a higher risk for developing MSI-H CRC compared to controls (P=0.01, OR=3.182 and P=0.005, OR=3.594, respectively). The most significant MSI-H-associated risk haplotypes include the most frequent haplotype H1 (T-C-T-T) defined by SNPs in exon 12, intron 13 (rs2235035), exon 21, and exon 26 (3435 C-->T; P=0.004, OR= 0.476). Our results suggest that ABCB1/MDR1 is a novel low-penetrance gene for susceptibility to MSI-H tumors. The present study provides additional evidence for the role that the MDR1/ABCB1 gene plays in the initiation and progression of MSI-H CRC development.


Neuroendocrine Disruptions Following Head Injury.
This article reviews hypopituitarism after TBI, the importance of pituitary hormones, and related controversies, concluding with a suggested patient approach. While earlier studies focused on increased pituitary deficiencies after moderate-severe TBI, recent studies have focused on deficiencies after mild TBI. There has been increasing focus on the role of growth hormone after injury; growth hormone is the most frequent reported deficiency at 1 year post-TBI, and an area with unresolved questions. While more research is needed to quantify the risk of deficiencies in special populations, and establish the natural history, increasing data indicate an increase in hypopituitarism after other acquired brain injuries; the potential role of pituitary hormone deficiencies after stroke and after COVID-19 infection is an area of active inquiry. Given the negative health effects of untreated hypopituitarism and the opportunity to intervene via hormone replacement, it is important to recognize the role of pituitary hormone deficiencies after TBI.


Evidence for neurotransmitter plasticity in vivo: developmental changes in properties of cholinergic sympathetic neurons.
We have examined the cholinergic sympathetic innervation of sweat glands in footpads of adult and developing rats. Acetylcholinesterase staining reveals a plexus of heavily stained fibers in the sweat glands of adult rats. Reaction product appears among and around bundles of axons that lie at a considerable distance from the cells of the secretory tubule. Each bundle contains 8-12 axons that possess numerous varicosities and contain small clear and large dense core vesicles. The glands of the hindpaws and their innervation develop during the first three weeks after birth. Catecholamine-containing axons were associated with the forming glands. At 7 and 10 days, intensely fluorescent fibers surrounded the tubules, and all of the axon profiles associated with the glands contained small granular vesicles (SGV) after permanganate fixation to reveal vesicular stores of norepinephrine. At 14 days the sweat gland plexus was less intensely fluorescent than at earlier ages and relatively few SGV were present. By 21 days, no endogenous catecholamine fluorescence and no SGV were detectable. However, following exposure to exogenous catecholamine, fluorescent fibers were present in the sweat glands of mature rats and they corresponded in position and density to the plexus localized with acetylcholinesterase staining. Catecholamine uptake was blocked by incubation in the cold and by desmethylimipramine and was not observed in cholinergic parasympathetic fibers in the iris or salivary glands. After intraperitoneal administration of 5-hydroxydopamine and permanganate fixation, all the axons in the sweat glands contained a few SGV. Thus, the developing sweat glands appear to be innervated by noradrenergic axons that lose their stores of endogenous catecholamines but not their capacity for uptake and storage as they elaborate an axonal plexus in the maturing glands. These observations support the hypothesis that cholinergic sympathetic neurons appear to undergo a transition from noradrenergic to cholinergic function during development in vivo similar to that previously described in cell culture.


A stable cell line with a proportion of cells persistently infected with bovine viral diarrhoea virus.
Bovine turbinate (BTu) and lamb testis (LT) cell lines persistently infected with bovine viral diarrhoea virus (BVDV) arose as a result of a single change of medium containing commercial foetal calf serum. Infected cells comprise 30% and 50% respectively, of the total cell population, determined by immunohistochemical staining. The ratio of positive cells has remained unchanged during successive passages. Characterization of the persistently-infected BTu cells (BTuI) showed that only full length viral RNA was detected by northern blot hybridisation, indicating that DI particles were not involved. Secreted and intracellular virus from these cells was fully infectious for fresh BTu and LT cells. The BTuI cell line was fully permissive for a cytopathic BVDV isolate and a bovine herpesvirus, but non-permissive for two non-cytopathic BVDV isolates. Attempts to induce the permissive state in the BVDV-negative cells of the BTuI culture by treatment with actinomycin D and 5'-aza-cytidine failed. These cells provide a convenient model to study aspects of BVDV pathogenesis and replication.


Flow-injection chemiluminescence determination of chrysin and baicalein assisted by theoretical prediction of chemiluminescence behavior of chrysin and baicalein.
In this paper, the molecular connectivity indices were applied to theoretically predict the direct chemiluminescence (CL) behavior of chrysin and baicalein with our recently proposed discriminant function. Then, combined with flow-injection analysis, a new CL system for determination of chrysin and baicalein was proposed. The method was based on the oxidation of chrysin and baicalein by acidic KMnO(4) in the presence of formaldehyde to produce strong CL emission. The present paper suggested a new model to discover new CL analytical system: first, to theoretical predict the CL behavior, and the second, to suggest analytical system.


Malaria surveillance, outbreak investigation, response and its determinant factors in Waghemra Zone, Northeast Ethiopia: unmatched case-control study.
Malaria is a major global public health concern, with around half of the world's population at risk of infection. It is one of the most common epidemic-prone diseases, resulting in on-going epidemics and significant public health problems. On September 12, 2022, Waghemra Zone malaria monitoring data revealed that the district was suffering an unusually high number of malaria cases. Therefore, the aim of this study was to assess the occurrence of malaria outbreaks and investigate contracting factors in Waghemra Zone, Northeast Ethiopia. A community-based case-control study with a 1:1 ratio was employed at Waghemra Zone from September 14 to November 27, 2022. A total of 260 individuals (130 cases and 130 controls) were included in the study. A structured questionnaire was used to collect the data. Malaria cases were confirmed by either microscopy or malaria rapid diagnostic tests. The magnitude of the outbreak was described by place, person, and time. A multivariable logistic regression analysis was conducted to identify malaria risk factors. A total of 13,136 confirmed cases of malaria were detected in the Waghemra zone, with an overall attack rate of 26.5 per 1000 and slide positivity rate was 43.0%. The predominant species was Plasmodium falciparum accounting for 66.1%. Children under five years old (AOR = 5.1; 95% CI 2.6-23.0), the presence of artificial water-holding bodies (AOR: 2.7; 95% CI 1.340-5.420), intermittent rivers closer to the living house (AOR = 4.9; 95% CI 2.51-9.62), sleeping outside a home (AOR = 4.9; 95% CI 2.51-9.62), and a lack of knowledge about malaria transmission and prevention (AOR: 9.7; 95% CI 4.459-20.930) were factors associated with malaria contraction. The overall attack rate for malaria during this outbreak was high. Children less than five years, the presence of mosquito breeding sites, staying outdoors overnight, and a lack of knowledge on malaria transmission and prevention were predictors of malaria. Early management of local vector breeding places, as well as adequate health education on malaria transmission and prevention methods, should be provided to the community to prevent such outbreaks in the future.


Neck circumference as an indicator of elevated blood pressure independent from body composition: implications from the China nation health survey (CNHS).
The independent association of neck circumference (NC) on elevated blood pressure is still uncertain in adults of China. The aim of this study is to explore such association and investigate the predictive value of NC on hypertension. A total of 4279 adults aged 20-80 years participated in the cross-sectional study in 2014. Anthropometric information, NC, body composition indexes such as waist circumference, hip circumference and body fat percentage, and blood pressure were measured. General linear regression model was used to explore the association between NC and blood pressure; Logistic regression models were fitted to calculate the multi-variable adjusted prevalence, and the association of NC with hypertension. The overall prevalence of hypertension and pre-hypertension were 11.05 and 23.63%, respectively. NC was positively associated with both SBP and DBP (p < 0.001). The adjusted prevalence of hypertension increased with elevated NC quartiles in both sexes (p for trend < 0.001), from 17.81 to 42.93% in male and 9.72 to 21.31% in female. For male, NC was only associated with hypertension (OR: 1.15, 95% CI: 1.05-1.25) but not with pre-hypertension (OR: 0.97, 95% CI: 0.88-1.06). However, in female, NC was associated with both pre-hypertension and hypertension, the BMI adjusted ORs were 1.15 (1.03-1.28) and 1.24 (1.14-1.34). The sex-specific AUCs for NC predicting hypertension were 0.633 in male and 0.663 in female, similar with AUCs of other body fat indexes. NC was associated with both pre-HTN and HTN independent from other body composition indexes. NC is a simple and useful anthropometric index to identify elevated blood pressure in Chinese adults.


On the development of the cerebellum of the trout, Salmo gairdneri. II. Early development.
The early histogenesis of the cerebellum of Salmo gairdneri RICHARDSON, 1836 has been studied in fish ranging in length from about 5 to 14 mm, both with light microscopical and electron microscopical techniques. Structurally, the matrix cells correspond to those of other vertebrates. Mitoses occur predominantly at the ventricular surface, but peripheral mitoses are found as well, particularly in the period of highest mitotic activity. Mantle cell somata can be distinguished from the elongated matrix cells on the basis of their rounded shape. The neurogenetic and gliogenetic periods overlap considerably. Presumably the first mantle cells are all neuroblasts: as soon as the mantle layer starts to form, axonal profiles are found. In a slightly later stage glial differentiation is manifest in the radial processes contacting the meningeal surface. In young stages a distinction between neuroblasts and glioblasts can only be made on the basis of the structure of their processes. Processes of glioblasts can be distinguished from axons and dendrites by their paucity of microtubules. Dendrites, appearing in late-embryonic stages, contain the same organelles as axons, but in larger amounts. The first differentiation of mantle cell somata is an increase of rough endoplasmic reticulum, and that to a lesser degree in glioblasts than in neuroblasts. Neuronal nuclei are rounded and more electronlucent than those of mantle cells. Apart from zonulae adhaerentes between the internal processes of matrix cells, puncta adhaerentia occur frequently in the cerebellar anlage. However, they rarely occur on young neuron;. The possible significance of these junctions is discussed. The present study indicates that growth cones and filopodia are characteristic of most and probably of all types of cells in the early developing cerebellum. Growth cones contain much vesicular and tubular endoplasmic reticulum and in filopodia a fine filamentous network is present. In the somata of mantle cells growth areas were found, i.e. areas under the cell membrane with a similar content as growth cones. It is suggested that these areas anticipate the outgrowth of a new process.


[The use of indomethacin in acute intestinal infections].
The dynamics of the level of prostaglandins E and F was studied in 45 patients with bacterial intestinal infections. It was established that during the acute period of the disease their content showed a significant increase. Inclusion of the indomethacin (a prostaglandin inhibitor) in the complex pathogenetic treatment of intestinal infections promotes early disappearance of pathological symptoms of the disease.


Clonal structure of Staphylococcus aureus colonizing children with sickle cell anaemia and healthy controls.
Children with sickle cell anaemia (SCA) might carry hospital-associated bacterial lineages due to frequent hospital stays and antibiotic treatments. In this study we compared Staphylococcus aureus from SCA patients (n=73) and healthy children (n=143) in a cross-sectional study in Gabon. S. aureus carriage did not differ between children with SCA (n=34, 46∙6%) and controls matched for age, residence and sex (n=67, 46∙9%). Both groups shared similar S. aureus genotypes. This finding points towards a transmission of S. aureus between both groups in the community. We conclude that resistance rates from population-based studies with healthy participants could therefore also be used to guide treatment and prophylaxis of endogenous infections in children with SCA despite a different selection pressure.


Projections of excess deaths related to cold spells under climate and population change scenarios: A nationwide time series modeling study.
Future climate change is likely to alter cold spell-related disease burden. Few projection studies have considered the potential impact of the aging population with changing population size on cold spell-related disease burdens. We derived the association between cold spells and daily mortality for 272 main cities in mainland China. We combined these associations with modeled daily temperatures from three different climate models under two climate change scenarios and three population scenarios to project excess deaths related to cold spells. Furthermore, we used the factor separation method to calculate the independent contribution of future population size, age structure, and climate change on projected deaths attributable to cold spells. Compared to the baseline period, future excess deaths related to cold spells are expected to increase over most of the decades under RCP 2.6 (81.5% in 2050 s and 37% in 2090 s) and RCP 4.5 (55.5% in 2050 s and -19% in 2090 s). The factor analysis indicated that the rise of the aged population (≥65) substantially would amplify the excess deaths related to cold spells (increase by 101.1% in the 2050 s and 146.2% in the 2090 s). For the near future (2021-2040), population aging could fully offset the influence of decreased cold-spell days. In the middle of this century (2051-2070), the total excess deaths will exhibit significant variation across three scenarios. By the end of 21 century (2081-2100), the population shrinking would reduce the total excess deaths. Excess deaths related to cold spells may still increase in a warming climate and future demographic shifts would produce considerable influences in this increase for different periods.


An extruded encircling band straddling the cornea and corneal groove formation.
The authors report a rare consequence of an anteriorly migrated encircling silicone band. The extruded encircling band, which "cheesewired" forward through the superior and medical rectus insertions straddled the cornea firmly and formed a corneal groove. Corneal groove is an extremely rare complication of scleral buckling surgery.


Research Partnerships with Patients Living with Type 2 Diabetes: Practices and Challenges in Quebec Among People New to Canada.
Patients are increasingly encouraged to participate in health research programs as partners, with the aim to ensure that studies address their priorities. In response, the Strategy for Patient-Oriented Research (SPOR) has been created in Canada to transform the patient's role in research from a passive beneficiary to a more proactive partner of change within the healthcare system. This research investigates what people new to Canada living with type 2 diabetes think about participating in research partnerships. Using an ethnographic approach, 31 people new to Canada with a diagnosis of type 2 diabetes were interviewed. Findings indicated that few people new to Canada were represented among the Diabetes Action Canada (DAC) Network's Circles of Patient Partners in Quebec. Barriers to engagement in research were: lack of information; competing priorities; language barrier and privacy concerns; preconceptions about being a patient partner; prejudices on research engagement as something demanding and binding; and the matter of religious and gender differences. Some participants questioned the extent to which involvement in research can really meet their expectations considering institutional control over research, funding requirements that often dictate priorities and the biomedical approach which still, in many respects, dominates health research. Implications for achieving equity, diversity, and inclusion of patient partners in research are discussed.


Extreme lateral lumbar disc herniations. Clinical syndrome and computed tomography recognition.
The clinical histories of four patients with extreme lateral lumbar disc herniations are presented to demonstrate the ineffectiveness of myelography and the value of computed tomography.


Detection of intra-amniotic infection in a rabbit model by proteomics-based amniotic fluid analysis.
This study was undertaken to identify intra-amniotic infection caused by several different organisms in a rabbit model by using proteomics. Twenty infected and 18 uninfected amniotic fluid samples were subjected to proteomic analysis by surface-enhanced laser desorption ionization (SELDI-TOF, Ciphergen Biosystems, Fremont, Calif), 1- and 2-dimensional gel electrophoresis, and tandem mass spectrometry (MS/MS). Detailed SELDI-TOF spectra revealed a constitutive 4.0 kd peak in all animals. Infected samples also displayed a signature double peak at 3.6 kd. A SELDI-TOF signature profile for intra-amniotic infection predicted positive amniotic fluid and/or fetal cultures with a sensitivity of 90% and specificity of 83%. Similar proteomic profiles were obtained regardless of the infecting organism. The 3.6 kd peak appeared to contain rabbit calgranulin C and rabbit calcyclin, members of the S100 family of calcium binding proteins. Amniotic fluid proteomic analysis was able to detect intra-amniotic infection in this experimental rabbit model. S100 proteins may be involved in the host inflammatory response to intra-amniotic infection.


Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke.
A reversible model of focal thrombotic stroke was developed in the rat and examined for histological evidence of reperfusion injury after clinically relevant times of recanalization. The distal middle cerebral artery of 28 male Sprague-Dawley rats was occluded by 562-nm laser-driven photothrombosis for 0.5, 2, and 3 hours or permanently (each n=7) and was recanalized by 355-nm UV laser irradiation. Occlusive material was examined by transmission electron microscopy. Cortical cerebral blood flow was monitored by laser-Doppler flowmetry. Brain infarcts were examined histologically at 3 days. After occlusion, cortical cerebral blood flow was reduced to 33+/-4% of baseline for all groups and was restored to 82+/-9%, 75+/-3%, and 93+/-7% of baseline for the 0.5-, 2-, and 3-hour groups, respectively, following recanalization after 29+/-8, 38+/-20, and 70+/-33 minutes of UV laser irradiation. The thrombotic occlusion contained compactly aggregated platelets but no fibrin, with length (1.2 to 1.8 mm) proportional to the ischemic period. During recanalization, microchannels containing erythrocytes and scattered leukocytes and bordered by intact disaggregated platelets infiltrated the thrombus. Infarct volumes (mm3) at 3 days were 12+/-3 for the permanent case and 8+/-4, 24+/-3, and 30+/-9 for the 0.5-, 2-, and 3-hour cases, respectively, thus demonstrating reperfusion injury histologically in the latter 2 groups. No hemorrhage was seen. UV laser-facilitated dissolution of a conventionally refractory platelet thrombus provides a novel and effective method for restoring blood flow without hemorrhagic complications during thrombotic stroke. This was the first observation of histologically confirmed reperfusion injury in such a model.


ABL1 regulates spindle orientation in adherent cells and mammalian skin.
Despite the growing evidence for the regulated spindle orientation in mammals, a systematic approach for identifying the responsible genes in mammalian cells has not been established. Here we perform a kinase-targeting RNAi screen in HeLa cells and identify ABL1 as a novel regulator of spindle orientation. Knockdown of ABL1 causes the cortical accumulation of Leu-Gly-Asn repeat-enriched-protein (LGN), an evolutionarily conserved regulator of spindle orientation. This results in the LGN-dependent spindle rotation and spindle misorientation. In vivo inactivation of ABL1 by a pharmacological inhibitor or by ablation of the abl1 gene causes spindle misorientation and LGN mislocalization in mouse epidermis. Furthermore, ABL1 directly phosphorylates NuMA, a binding partner of LGN, on tyrosine 1774. This phosphorylation maintains the cortical localization of NuMA during metaphase, and ensures the LGN/NuMA-dependent spindle orientation control. This study provides a novel approach to identify genes regulating spindle orientation in mammals and uncovers new signalling pathways for this mechanism.


A general approach for automatic segmentation of pneumonia, pulmonary nodule, and tuberculosis in CT images.
Proposing a general segmentation approach for lung lesions, including pulmonary nodules, pneumonia, and tuberculosis, in CT images will improve efficiency in radiology. However, the performance of generative adversarial networks is hampered by the limited availability of annotated samples and the catastrophic forgetting of the discriminator, whereas the universality of traditional morphology-based methods is insufficient for segmenting diverse lung lesions. A cascaded dual-attention network with a context-aware pyramid feature extraction module was designed to address these challenges. A self-supervised rotation loss was designed to mitigate discriminator forgetting. The proposed model achieved Dice coefficients of 70.92, 73.55, and 68.52% on multi-center pneumonia, lung nodule, and tuberculosis test datasets, respectively. No significant decrease in accuracy was observed (p > 0.10) when a small training sample size was used. The cyclic training of the discriminator was reduced with self-supervised rotation loss (p < 0.01). The proposed approach is promising for segmenting multiple lung lesion types in CT images.


Solution NMR structure of the DNA-binding domain from Scml2 (sex comb on midleg-like 2).
Scml2 is a member of the Polycomb group of proteins involved in epigenetic gene silencing. Human Scml2 is a part of a multisubunit protein complex, PRC1 (Polycomb repressive complex 1), which is responsible for maintenance of gene repression, prevention of chromatin remodeling, preservation of the "stemness" of the cell, and cell differentiation. Although the majority of PRC1 subunits have been recently characterized, the structure of Scml2 and its role in PRC1-mediated gene silencing remain unknown. In this work a conserved protein domain within human Scml2 has been identified, and its structure was determined by solution NMR spectroscopy. This module was named Scm-like embedded domain, or SLED. Evolutionarily, the SLED domain emerges in the first multicellular organisms, consistent with the role of Scml2 in cell differentiation. Furthermore, it is exclusively found within the Scm-like family of proteins, often accompanied by malignant brain tumor domain (MBT) and sterile α motif (SAM) domains. The domain adopts a novel α/β fold with no structural analogues found in the Protein Data Bank (PDB). The ability of the SLED to bind double-stranded DNA was also examined, and the isolated domain was shown to interact with DNA in a sequence-specific manner. Because PRC1 complexes localize to the promoters of a specific subset of developmental genes in vivo, the SLED domain of Scml2 may provide an important link connecting the PRC1 complexes to their target genes.


Full publication of abstracts of randomised controlled trials published at International Continence Society meetings'.
To find out how many abstracts reporting randomised controlled trials (RCTs) that are submitted to scientific meetings of the International Continence Society (ICS) are later published in full, and any predictors of full publication. The appropriate issues of "Neurourology and Urodynamics" and the Proceedings of the ICS for 1998 and 1999 were hand-searched for the abstracts reporting RCTs. Bibliographic databases (Cochrane Controlled Trials Register, MEDLINE, EMBASE, Healthstar, Psychlit, CINAHL) were searched, using the authors' names, to find full publications. Authors were contacted when no full publication was found to check that all full publications had been found. This was repeated for 1987. Sixty-three abstracts reporting RCTs were found in 1998 and 1999. Twenty-five of these (40%) were followed by full publication. The only characteristic that predicted full publication was the use of a no treatment control group. In 1987, 16 of 19 abstracts (84%) went on to be published in full. The rate of full publication of abstracts reporting RCTs submitted to recent ICS meetings is low. It is lower than the rate of 56% found in other meetings. As it is widely regarded as unethical not to publish in full, ICS members should make every effort to write-up studies for peer-reviewed publication.


Insight into the specificity and severity of pathogenic mechanisms associated with missense mutations through experimental and structural perturbation analyses.
Most pathogenic missense mutations cause specific molecular phenotypes through protein destabilization. However, how protein destabilization is manifested as a given molecular phenotype is not well understood. We develop here a structural and energetic approach to describe mutational effects on specific traits such as function, regulation, stability, subcellular targeting or aggregation propensity. This approach is tested using large-scale experimental and structural perturbation analyses in over thirty mutations in three different proteins (cancer-associated NQO1, transthyretin related with amyloidosis and AGT linked to primary hyperoxaluria type I) and comprising five very common pathogenic mechanisms (loss-of-function and gain-of-toxic function aggregation, enzyme inactivation, protein mistargeting and accelerated degradation). Our results revealed that the magnitude of destabilizing effects and, particularly, their propagation through the structure to promote disease-associated conformational states largely determine the severity and molecular mechanisms of disease-associated missense mutations. Modulation of the structural perturbation at a mutated site is also shown to cause switches between different molecular phenotypes. When very common disease-associated missense mutations were investigated, we also found that they were not among the most deleterious possible missense mutations at those sites, and required additional contributions from codon bias and effects of CpG sites to explain their high frequency in patients. Our work sheds light on the molecular basis of pathogenic mechanisms and genotype-phenotype relationships, with implications for discriminating between pathogenic and neutral changes within human genome variability from whole genome sequencing studies.


Additive manufacturing of multi-material parts - Design guidelines for manufacturing of 316L/CuCrZr in laser powder bed fusion.
Additive manufacturing (AM) can be used to produce multi-material parts in which the material can be varied voxel-wise in all three spatial directions. This means that the paradigm of the homogeneous material can be abandoned and local effects such as heat conduction or damping can be selectively adjusted in the part. Recently, continuous development of machine technology has allowed the production of multi-metal materials in laser powder bed fusion (PBF-LB/MM). Compared to other additive manufacturing processes for multi-material production, this allows greater design freedom and detail accuracy to be realized. However, due to the novel character of multi-material manufacturing in PBF-LB, the process knowledge for successful and reproducible fabrication is currently lacking. This paper focuses on establishing design guidelines for manufacturing the material pairing of stainless steel 316L (1.4404) and copper alloy CuCrZr (CW106C). The article is accompanied by the development of a specific process chain. As a result of this work, design guidelines for multi-material parts are available for the first time, in regard to arrangement, size, overhangs, economy, powder quality and laser scanning.


Internal standardization combined with dilute-and-shoot preparation of distilled alcoholic beverages for Cu determination by high-resolution continuum source flame atomic absorption spectrometry.
Internal standardization (IS) and dilute-and-shoot preparation of distilled alcoholic beverages were evaluated for the direct determination of Cu by high-resolution continuum source flame atomic absorption spectrometry. Among Bi, In, Sn and Te evaluated as internal standards, Bi and Te furnished best results. Calibration curves were built up by plotting A(Cu)/A(Bi) and A(Cu)/A(Te)versus Cu concentration (0.05-4.0 mg L(-1)) and linear correlation coefficients were 0.9994 and 0.9990, respectively. Contents of Cu in 22 commercial distilled beverages analyzed by the proposed method varied in the 0.029-3.608 mg L(-1) interval. These results were in agreement (paired t-test) at 95% confidence level with those obtained by line source FAAS using standard addition calibration. Recoveries improved from 77-83% (without IS) to 99-101% (with IS) intervals. The relative standard deviation (n=12) was 0.8-3.7% (IS-Bi), 0.4-4.4% (IS-Te), and 0.5-9.1% (without IS) and the limit of detection was ca. 5 μg L(-1) using Bi or Te.


Mesothelial primary cilia of peritoneal and other serosal surfaces.
The conspicuous presence of primary cilia, a small immotile cilium present on most cell types, left researchers with little doubt of their functional relevance. Recently mechanosensitive functional significance was established and a link with the pathogenesis of polycystic kidney disease. Together these discoveries have raised the profile of this, previously considered "vestigial", organelle. Primary cilia are expressed on the apical surface of serosal mesothelium and display regional variation but are more abundant on biosynthetically active cells. Adult mesothelial cells are highly biosynthetic producing a phospholipid rich surfactant that lubricates and protects the visceral organs. The mesothelium is utilized as a semipermeable membrane during peritoneal dialysis for patients with end stage renal failure. However, little is known about the functional role of primary cilia on this highly specialized cell type. The present review, examines the significance of the primary cilium in serosal mesothelial cell biology with an emphasis on ciliary location, structure, form and function. Future research is identified and discussed in view of the emerging role cilia have in other cells and the established function of the serosal mesothelium in development, normal function, peritoneal dialysis and pathology of the serosal membranes.


A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics.
Despite the growing threat of antimicrobial resistance, pharmaceutical and biotechnology firms are reluctant to develop novel antibiotics because of a host of market failures. This problem is complicated by public health goals that demand antibiotic conservation and equitable patient access. Thus, an innovative incentive strategy is needed to encourage sustainable investment in antibiotics. This systematic review consolidates, classifies and critically assesses a total of 47 proposed incentives. Given the large number of possible strategies, a decision framework is presented to assist with the selection of incentives. This framework focuses on addressing market failures that result in limited investment, public health priorities regarding antibiotic stewardship and patient access, and implementation constraints and operational realities. The flexible nature of this framework allows policy makers to tailor an antibiotic incentive package that suits a country's health system structure and needs.


Neonatal cardiac output measurement using pulsed Doppler ultrasound.
Recent developments in range-gated pulsed Doppler ultrasound velocimetry have offered a noninvasive technique for the quantitative measurement of blood flow and cardiac output that can be applied to the neonate and small infant. If used appropriately, pulsed Doppler ultrasound can be useful in clinical management of the ill neonate and can improve our understanding of cardiovascular physiology in both normal developmental and pathologic states.


Allorecognition proteins in an invertebrate exhibit homophilic interactions.
Sessile colonial invertebrates-animals such as sponges, corals, bryozoans, and ascidians-can distinguish between their own tissues and those of conspecifics upon contact [1]. This ability, called allorecognition, mediates spatial competition and can prevent stem cell parasitism by ensuring that colonies only fuse with self or close kin. In every taxon studied to date, allorecognition is controlled by one or more highly polymorphic genes [2-8]. However, in no case is it understood how the proteins encoded by these genes discriminate self from non-self. In the cnidarian Hydractinia symbiolongicarpus, allorecognition is controlled by at least two highly polymorphic allorecognition genes, Alr1 and Alr2 [3, 5, 9-12]. Sequence variation at each gene predicts allorecognition in laboratory strains such that colonies reject if they do not share a common allele at either locus, fuse temporarily if they share an allele at only one locus, or fuse permanently if they share an allele at both genes [5, 9]. Here, we show that the gene products of Alr1 and Alr2 (Alr1 and Alr2) are self-ligands with extraordinary specificity. Using an in vitro cell aggregation assay, we found that Alr1 and Alr2 bind to themselves homophilically across opposing cell membranes. For both proteins, each isoform bound only to itself or to an isoform of nearly identical sequence. These results provide a mechanistic explanation for the exquisite specificity of Hydractinia allorecognition. Our results also indicate that hydroids have evolved a molecular strategy of self-recognition that is unique among characterized allorecognition systems within and outside invertebrates.


Bioavailability and impacts of estrogenic compounds from suspended sediment on rainbow trout (Oncorhynchus mykiss).
Numerous environmental pollutants have the potential to accumulate in sediments, and among them are endocrine-disrupting chemicals (EDCs). It is well documented that water-borne exposure concentrations of some potent EDCs, more specifically estrogenic- active compounds (ECs), can impair the reproduction of fish. In contrast, little is known about the bioavailability and effects of sediment-associated ECs on fish. Particularly, when sediments are disturbed, e.g., during flood events, chemicals may be released from the sediment and become bioavailable. The main objectives of this study were to evaluate a) whether ECs from the sediment become bioavailable to fish when the sediment is suspended, and b) whether such exposure leads to endocrine responses in fish. Juvenile rainbow trout (Oncorhynchus mykiss) were exposed over 21 days to constantly suspended sediments in the following treatments: i) a contaminated sediment from the Luppe River, representing a "hotspot" for EC accumulation, ii) a reference sediment (exhibiting only background contamination), iii) three dilutions, 2-, 4- and 8-fold of Luppe sediment diluted with the reference sediment, and iv) a water-only control. Measured estrogenic activity using in vitro bioassays as well as target analysis of nonylphenol and estrone via LC-MS/MS in sediment, water, fish plasma, as well as bile samples, confirmed that ECs became bioavailable from the sediment during suspension. ECs were dissolved in the water phase, as indicated by passive samplers, and were readily taken up by the exposed trout. An estrogenic response of fish to Luppe sediment was indicated by increased abundance of transcripts of typical estrogen responsive genes, i.e. vitelline envelope protein α in the liver and vitellogenin induction in the skin mucus. Altered gene expression profiles of trout in response to suspended sediment from the Luppe River suggest that in addition to ECs a number of other contaminants such as dioxins, polychlorinated biphenyls (PCBs) and heavy metals were remobilized during suspension. The results of the present study demonstrated that sediments not only function as a sink for ECs but can turn into a significant source of pollution when sediments are resuspended as during flood-events. This highlights the need for sediment quality criteria considering bioavailability sediment-bound contaminants in context of flood events.


Keratoacanthoma formation after skin grafting: A brief report and pathophysiological hypothesis.
Keratoacanthoma formation after skin grafting is rare. We report the third case in the literature of multiple keratoacanthomas developed at both split-thickness skin graft donor and recipient sites. We provide possible explanations for this poorly understood phenomenon and highlight its implications on treatment options.


Assessment of global fish footprint reveals growing challenges for sustainable production and consumption.
Globalization faces a tradeoff between meeting fish consumption demand for nutritious & healthy living and reducing the ecological footprint to achieve sustainable development. Here, we document drivers, historical trends, and mitigation options for global fish footprint using unevenly spaced data spanning 1961 to 2021 from over 200 economies while accounting for income classifications. We report a decline in fish production in developed countries, yet, their increased consumption demand per capita is met through overexploited stocks of fish imported from developing economies. Besides, global fish price volatility has no effect on fish distribution in high-income nations but highly influences fish production, consumption, import, and export in developing nations. The evidence of purchasing economies of scale in urbanized countries and the potential threat of embodied price in fish distribution and trade affect global fish footprint. The persistent increase in fish footprint can be attributed to affluence, choice of technology, urbanization, human development, marine trophic levels, emission intensity, and time-invariant & unobserved country-specificities. We highlight that aligning development and choices along the targets of sustainable development goals augments the achievement of sustainable fish production and consumption.


The Medical Research Council Hypertension Trial: the smoking patient.
Tobacco smoking is a powerful risk predictor for coronary disease. In the recent Medical Research Council (MRC) Hypertension Trial, which this article discusses, it also proved to be an important predictor of stroke. The MRC trial had two active treatment groups, one of which received bendrofluazide and the other propranolol. The main positive result of the trial was a 45% reduction in stroke events in the actively treated groups. Propranolol appeared to be much less effective than bendrofluazide in the prevention of stroke in smokers, although both active drugs were equally effective in nonsmokers. Possible explanations for this lack of efficacy in smokers are discussed. Coronary events were not reduced by treatment, although there was a trend toward their reduction in nonsmoking men treated with propranolol. The lack of effect of propranolol in reducing coronary morbidity and mortality rates was a surprise in view of the positive results from trials with both short-term and long-term treatment with beta-adrenergic blockade after myocardial infarction.


Hepatocyte growth factor fusion protein having collagen-binding activity (CBD-HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.
Hepatocyte growth factor (HGF) is known to stimulate endothelial cell proliferation. However, re-endothelialization is not enhanced when the native protein is administered to the injured artery, probably due to the short half-life of HGF at the site of injury. Therefore, the effects of an HGF fusion protein having collagen-binding activity (CBD-HGF) on re-endothelialization and neointimal formation was studied in the balloon-injured rat carotid artery. The left common carotid artery of male Sprague-Dawley rats was injured with an inflated balloon catheter, and then treated with CBD-HGF 10 microg/mL), HGF (10 micro g/mL) or saline (control) for 15 min. After 14 days, the rats were injected with Evans blue and sacrificed. The re-endothelialized area was significantly greater in the CBD-HGF- treated rats than in the control or HGF -treated rats. Neointimal formation was significantly more pronounced in the CBD-HGF treated rats than in other rat groups. Both HGF and CBD-HGF stimulated proliferation of vascular smooth muscle cells as well as endothelial cells in vitro. Consistent with this, cultured smooth muscle cells were shown to express the HGF receptor (c-Met). CBD-HGF accelerates re-endothelialization and neointimal formation in vivo. CBD fusion protein is a useful vehicle to deliver vascular growth factors to injured arteries.


Primary treatment of nasolacrimal duct obstruction with balloon catheter dilation in children younger than 4 years of age.
To report the outcome of nasolacrimal duct balloon catheter dilation as the primary treatment of congenital nasolacrimal duct obstruction (NLDO) in children younger than 4 years of age. One hundred two children (151 eyes) ages 12 to <48 months (mean, 23 months) at the time of surgery, who previously had not undergone a nasolacrimal surgical procedure and who presented with at least one of the following clinical signs of NLDO--epiphora, increased tear lake, and/or mucous discharge--were enrolled in a prospective, nonrandomized observational multicenter study (20 sites). All children received balloon catheter dilation of the nasolacrimal system of the affected eye(s). Treatment success was defined as no epiphora, increased tear lake, and/or mucous discharge present at the outcome visit at 1 month after surgery. The proportion of eyes treated successfully was 82% (95% CI: 74%-88%). The dye disappearance test at outcome was normal in 105 (73%), indeterminate in 15 (10%), and abnormal in 23 (16%) of the 143 eyes tested. In children 12 to <48 months of age, balloon catheter dilation as a primary treatment of NLDO was successful in approximately 80% of cases. Because we did not perform a randomized trial with a comparison group, we were unable to determine how this procedure's success rate compares with that of simple probing or nasolacrimal intubation in this age group.


Homozygous familial hypobetalipoproteinemia: A Turkish case carrying a missense mutation in apolipoprotein B.
The autosomal co-dominant disorder familial hypobetalipoproteinemia (FHBL) may be due to mutations in the APOB gene encoding apolipoprotein B (apoB), the main constituent peptide of chylomicrons, very low and low density lipoproteins. We describe an 11month-old child with failure to thrive, intestinal lipid malabsorption, hepatic steatosis and severe hypobetalipoproteinemia, suggesting the diagnosis of homozygous FHBL, abetalipoproteinemia (ABL) or chylomicron retention disease (CMRD). The analysis of candidate genes showed that patient was homozygous for a variant (c.1594 C>T) in the APOB gene causing arginine to tryptophan conversion at position 505 of mature apoB (Arg505Trp). No mutations were found in a panel of other potential candidate genes for hypobetalipoproteinemia. In vitro studies showed a reduced secretion of mutant apoB-48 with respect to the wild-type apoB-48 in transfected McA-RH7777 cells. The Arg505Trp substitution is located in the βα1 domain of apoB involved in the lipidation of apoB mediated by microsomal triglyceride transfer protein (MTP), the first step in VLDL and chylomicron formation. The patient's condition improved in response to a low fat diet supplemented with fat-soluble vitamins. Homozygosity for a rare missense mutation in the βα1 domain of apoB may be the cause of both severe hypobetalipoproteinemia and intestinal lipid malabsorption.


Human heat shock protein 60 stimulates vascular smooth muscle cell proliferation through Toll-like receptors 2 and 4.
Heat shock proteins (HSPs) of endogenous and exogenous origin are suspected contributors to the initiation and aggravation of vascular pathologies like atherosclerosis and restenosis. Toll-like receptors (TLRs) 2 and 4 are well-known receptors for exogenous pathogen-associated molecular patterns and have recently been thought to play a role in HSP60-induced cellular activation. We hypothesized that human HSP60 directly stimulates venous smooth muscle cell (VSMC) proliferation through a TLR-dependent mechanism. Localization of HSP60, TLR2 and TLR4 was studied in failed venous grafts and normal venous tissue by double immunostaining. In vitro VSMCs were incubated for 48 h with recombinant human HSP60. In other experiments, VSMCs were pre-incubated for 30 min with specific anti-TLR2 and anti-TLR4 antibodies. VSMC proliferation was determined by Ki67 immunoreactivity, and mean values were compared between experimental and control groups. In addition, human embryonic kidney (HEK) cells transfected with human TLR2 or TLR4/MD-2 were exposed to HSP60 for 48 h, and proliferation was determined by using a hemocytometer. Co-localization of HSP60 and TLRs was detected in all neointimal lesions but was virtually absent in normal veins. Human HSP60 stimulated VSMC proliferation in a concentration-dependent fashion. In addition, TLR2 and TLR4 antibodies attenuated VSMC proliferation. The role of TLR-mediated stimulation of cell proliferation by HSP60 was supported by the significant increase in proliferation of transfected HEK cells. These findings provide supporting evidence for the role of HSP60 and TLR2 and TLR4 in vascular disease. Moreover, our data surpass the infection- and autoimmunity-based hypotheses of cardiovascular disease and suggest an additional HSP60-related autocrine process.


[The current status and place of open surgery in treating urolithiasis].
Within the concept of treatment of urinary calculosis, open surgery still occupies a firm place. At present, however, the indications for open surgical interventions have been considerably narrowed, and only a small group of patients with urinary calculosis are subject of open surgery, which requires experienced operators and special instruments for optimally sparing performance of the operation. Often intraoperative echography makes useless the application of intraoperative hypothermia and intraoperative X-ray diagnosis.


Association of 11 variants of the dopaminergic and cognitive pathways genes with major depression, schizophrenia and bipolar disorder in the Pakistani population.
Background: The dopaminergic pathways control neural signals that modulate mood and behaviour along and have a vital role in the aetiology of major depression (MDD), schizophrenia (SHZ) and bipolar disorder (BD). Genome-wide association studies (GWAS) have reported several dopaminergic and cognitive pathway genes association with these disorders however, no such comprehensive data was available regarding the Pakistani population.Objective: The present study was conducted to analyse the 11 genetic variants of dopaminergic and cognitive system genes in MDD, SHZ, and BD in the Pakistani population.Methods: A total of 1237 subjects [MDD n = 479; BD n = 222; SHZ n = 146; and controls n = 390], were screened for 11 genetic variants through polymerase chain reaction (PCR) techniques. Univariant followed by multivariant logistic regression analysis was applied to determine the genetic association.Results: Significant risk associations were observed for rs4532 and rs1799732 with MDD; and rs1006737 and rs2238056 with BD. However, after applying multiple test corrections rs4532 and rs1799732 association did not remain significant for MDD. Moreover, a protective association was found for three variants; DRD4-120bp, rs10033951 and rs2388334 in the current cohort.Conclusions: The present study revealed the risk association of single nucleotide polymorphisms (SNPs) rs1006737 and rs2238056 with BD and the protective effect of the DRD4-120bp variant in MDD and BD, of rs2388334 in BD and of rs10033951 in MDD, BD, and SHZ in the current Pakistani cohort. Thus, the study is valuable in understanding the genetic basis of MDD, BD and SHZ in the Pakistani population, which may pave the way for future functional studies.


Prey selection by a stonefly: the influence of hunger and prey size.
The influences of hunger and prey size on prey selection by the stonefly Hesperoperla pacifica (Perlidae) were explored in the laboratory by observing behavioral responses toward ten prey taxa and three nonprey taxa. Patterns of behavior were consistent with most assumptions and predictions of optimal foraging theory predicting sizebased prey selection by pursuing predators. Handling time appeared to increase as an exponential function of prey mass, and prey profitability (mg/s) was highest for small and intermediate-sized prey. Fasted stoneflies consumed a wide range of prey sizes, whereas well-fed stoneflies concentrated their attacks on intermediate-sized prey. Responses of H. pacifica to nonprey taxa, however, suggest that prey recognition and selection are not based on size alone.


Central mu-opioid receptors are down-regulated in a rat model of cholestasis.
Ameliorations of the pruritus of cholestasis by opioid antagonists are consistent with this form of pruritus being centrally mediated by the opioid system. To determine whether the central opioid system is altered in cholestasis, the specific binding of a selective mu-opioid receptor ligand, 3H-DAMGO, to mu-opioid receptors was studied in rats with acute cholestasis due to bile duct resection. Using whole brain membranes and subcellular mitochondrial-synaptosomal fractions the density of mu-receptor sites was 30% (p less than 0.01) and 22% (p = 0.03) less in bile-duct-resected rats than in sham-resected rats. Using membranes from individual brain regions specific binding of 3H-DAMGO was reduced by 43-53% in the cerebral cortex, hippocampus and caudate nucleus of bile-duct-resected rats. Thus mu-opioid receptors in the brain are down-regulated in a classical model of cholestasis. This alteration of the central opioid system could be a consequence of increased exposure of opioid receptors to endogenous opioids in cholestasis and may reflect an important mechanism in the pathogenesis of the pruritus of cholestasis.


Sitagliptin as an Initial Therapy and Differential Regulations of Metabolic Parameters Depending on its Glycemic Response in Subjects with Type 2 Diabetes.
The aim of this study is to investigate whether sitagliptin can be used as an initial drug for T2DM and to evaluate its effects on metabolic parameters in relation to its glycemic efficacies. The subjects received 25-50 mg/day sitagliptin monotherapy (n=69). At 3 months, they were divided into three groups (n=23 each) according to the novel parameter called "A1c index" which is designed to assess glycemic efficacy. The metabolic parameters were compared between good-responders and poor-responders. These two groups acted as a control each other. In the overall subjects, efficient reductions of HbA1c (10.16-8.22%) were observed with few adverse events. Significant correlations were seen between the A1c index and changes of (∆)nonHDL-C (R=0.250) or ∆LDL-C (R=0.368). At baseline, T-C, nonHDL-C and BMI levels were significantly lower in good-responders than poor-responders. At 3 months, in good-responders, HbA1c levels effectively decreased (11.03-7.00%). Indexes for insulin sensitivity/resistance [HOMA-R and 20/(C-peptide x FBG)] and beta-cell function (HOMA-B and CPR-index) ameliorated. T-C, nonHDL-C and LDL-C significantly decreased, while BMI increased. However, in poor-responders, no changes in these parameters were noted. Collectively, these results suggest that 1) Sitagliptin can be used as a first-line drug for T2DM and its glycemic efficacy is linked to some atherogenic lipids. 2) Those with lower T-C, nonHDL-C and BMI appear to respond better with this drug. 3) Good glycemic efficacy of sitagliptin is medicated through reduced insulin resistance as well as enhanced beta-cell functions. Body weight increased, while some atherogenic cholesterol decreased in good-responders.


Congenital hypoplastic thumb in the Silver syndrome--a case report and review of upper extremity anomalies in the world literature.
A case of classical Silver syndrome presented with a congenital hypoplastic thumb, absent thenar musculature, and partial index ankylosis. No previous association of congenital hypoplastic thumb and the Silver syndrome has been noted by Dr. Silver or described in the world literature. Restoration of thumb function was achieved in this particular case by the abductor digiti minimi transfer described by Huber. The upper extremity anomalies thus far reported with Silver syndrome in the world literature are summarized.


Corrigendum to "The Effect of Sanggua Drink Extract on Insulin Resistance through the PI3K/AKT Signaling Pathway".
[This corrects the article DOI: 10.1155/2018/9407945.].


A comparative study on flavor trapping techniques from the viewpoint of odorants of hot-pressed rapeseed oil.
Rapeseed oil, as one of the three major vegetable oils in the world, its matrix effect makes the decoding flavor a challenge. Solid-phase microextraction (SPME), SPME-Arrow, headspace stir bar sorptive extraction (HSSE), direct thermal desorption (DTD), and solvent-assisted flavor evaporation (SAFE) were compared based on the odorants in hot-pressed rapeseed oil. Besides, methodological validation for 31 aroma standards was conducted to compare reliability and robustness of these approaches. DTD showed the largest proportion of acids, while the other techniques extracted a majority of nitriles. The highest number of odorants was detected by SAFE (31), followed by HSSE (30), SPME-Arrow (30), SPME (24), and DTD (14). SPME-Arrow showed the best performance in linearity, recovery, and reproducibility followed by SPME, HSSE, DTD, and SAFE. Results reveal the advantages and limitations of diverse methodologies and provide valuable insights for the selection of extraction methods in an oil matrix and flavor decoding.


The importance of preoperative imaging methods in reduction mammoplasty.
Breast reduction surgery is a common procedure in plastic surgery clinics, and there are varying practices regarding preoperative mammography and breast ultrasound in patients who have no history of cancer and no symptoms other than those caused by macromastia. In this study, we retrospectively analyzed the imaging findings of patients who presented to the plastic surgery outpatient clinic due to macromastia between January 1, 2006 and June 1, 2020 and underwent mammography and/or breast ultrasound for preoperative screening and breast magnetic resonance imaging for further examination. Patients with a history of breast cancer diagnosed prior to preoperative screening or any other breast disease were excluded. Radiologically suspicious findings were significantly more common in patients over 40 years of age and significantly less frequent in the group under 50 years of age. When the patients were grouped by the decade of life, the frequency of radiologically suspicious findings was significantly lower in the 20-29 group and significantly higher in the 40-49 and 50-59 groups. Malignancy was not detected by histopathological examination in any patient. Proliferative lesions were detected in 10 reduction mammoplasty specimens (2.4%) of 7 patients (3.1%). The correlation between radiological and histopathological findings may be weak in macromastia patients. Most suspicious radiological findings appear to be the population between 40 and 59 years of age .


Synthesis of 5-Aminoimidazole-4-Carboxamide Riboside (AICAR) and Its Derivatives Using Inosine as Starting Material.
This unit contains four basic protocols describing the synthesis of 5-aminoimidazole-4-carboxamide riboside (AICAR), 5-aminoimidazole-4-carboxamide riboside (ZPM), their 4-N functionalized derivatives, and two sugar-modified analogs of AICAR. The first and second basic protocols reveal the importance of solid-phase synthesis to obtain novel AICAR and ZMP imidazole-modified analogs in a short time, whereas the third and fourth basic protocols allow for the rapid preparation of 5'-F-AICAR and D-ribityl AICA.


Does variant luteinizing hormone (V-LH) predispose to improper testicular position in late pregnancy?
Undescended testes are a common urogenital malformation affecting 2-9% of newborn boys. The etiology of cryptorchidism is probably heterogeneous, but insufficient androgen effect has been recognized as one cause of the condition. A common genetic variant (V) form of LH occurs in apparently healthy individuals universally. Compared with wild-type (WT) LH, the V-LH molecule has increased bioactivity in vitro but shorter half-life in vivo. In the present study, we screened 93 cryptorchid (59 uni- and 34 bilateral) and 211 healthy boys for the occurrence of V-LH to evaluate whether it is related to testicular descent. Two immunofluorometric assays with different combinations of MAb, one detecting WT-LH, the other detecting both WT- and V-LH, were used to measure LH concentrations. The ratio of two LH measurements was used to assess the V-LH status. The prevalence of V-LH was similar in the control and cryptorchid groups, and the total prevalence of V-LH corresponded well to the prevalence of V-LH in general Finnish population. Among cryptorchid boys, the prevalence of V-LH was dependent on gestational age: 6.7% at GA <37, 20.9% at GA 37-39, and 42.9% at GA of 40-42 wk. In contrast, the percentage of V-LH status was similar at different gestational ages in all control groups. We conclude that V-LH is not critical for normal testicular descent but the increased prevalence of V-LH among cryptorchid boys with GA >40, suggests that the lower hormonal efficacy of V-LH predisposes for improper testicular descent in late pregnancy.


Application of a transition metal oxide/carbon-based nanocomposite for designing a molecularly imprinted poly (l-cysteine) electrochemical sensor for curcumin.
In this study an electrochemical sensor was fabricated for detection of curcumin, as a functional herbal food, using molecularly imprinted polymer and highly conductive transition metal oxide/carbon-based nanocomposite. In this way, CuCo2O4/nitrogen-doped carbon nanotubes/phosphorus-doped graphene oxide nanocomposite was dropped on the electrode. This nanocomposite synergically possesses conductivity features of copper and phosphorus-doping sites, specific surface area of carbon nanotubes, and carbons Fermi level of graphene oxide. In the following, l-Cystein electropolymerized on the electrode in presence of curcumin. The sensor was produced by removing curcumin from poly (L- cystein) matrix. The sensor was successfully used for detection of curcumin in the ranges of 0.1-1 µmol L-1 and 1-30 µmol L-1, with acceptable detection limit (30 nmol L-1). Finally, the proposed method was used for detection of curcumin in serum samples with recoveries of 80-110.87%. The results demonstrated that aforementioned method can be used for detection of curcumin in biological samples.


Reliability of graph analysis of resting state fMRI using test-retest dataset from the Human Connectome Project.
The exploration of brain networks with resting-state fMRI (rs-fMRI) combined with graph theoretical approaches has become popular, with the perspective of finding network graph metrics as biomarkers in the context of clinical studies. A preliminary requirement for such findings is to assess the reliability of the graph based connectivity metrics. In previous test-retest (TRT) studies, this reliability has been explored using intraclass correlation coefficient (ICC) with heterogeneous results. But the issue of sample size has not been addressed. Using the large TRT rs-fMRI dataset from the Human Connectome Project (HCP), we computed ICCs and their corresponding p-values (applying permutation and bootstrap techniques) and varied the number of subjects (from 20 to 100), the scan duration (from 400 to 1200 time points), the cost and the graph metrics, using the Anatomic-Automatic Labelling (AAL) parcellation scheme. We quantified the reliability of the graph metrics computed both at global and regional level depending, at optimal cost, on two key parameters, the sample size and the number of time points or scan duration. In the cost range between 20% to 35%, most of the global graph metrics are reliable with 40 subjects or more with long scan duration (14min 24s). In large samples (for instance, 100 subjects), most global and regional graph metrics are reliable for a minimum scan duration of 7min 14s. Finally, for 40 subjects and long scan duration (14min 24s), the reliable regions are located in the main areas of the default mode network (DMN), the motor and the visual networks.


Increased renal threshold of bicarbonate due to carbon dioxide retention associated with proximal renal tubular acidosis.
We report a neonate who manifested type II (proximal) renal tubular acidosis (RTA). Hypoventilation secondary to hypothalamic dysfunction led to carbon dioxide retention. The consequent changes in acid base regulation are detailed and discussed.


β-Glucan from mushrooms and dates as a wall material for targeted delivery of model bioactive compound: Nutraceutical profiling and bioavailability.
Rutin was nano-encapsulated in date [En-Ru(D)] and mushroom [En-Ru(M)] β-glucan matrix to protect it from the harsh gastrointestinal environment and to enhance its bioavailability and biological activity upon digestion. The encapsulation was carried using green technology i.e., ultra-sonication. The En-Ru(D) and En-Ru (M) showed the hydrodynamic diameter of 314.04 and 482.21 nm with polydispersity index of 0.21 and 0.33. The in vitro release behaviour followed the Higuchi model. The antimicrobial activity of En-Ru(D) and En-Ru(M) were evaluated against gram negative E. coli (ATCC 25922) and gram positive (Staphylococcus aureus) bacteria. Furthermore, En-Ru(D) and En-Ru(M) exhibited increased bioavailability of rutin in intestinal fluid with retention of anti-obesity and antioxidant activities after digestion (p < 0.05). Therefore, β-glucan matrix can efficiently encapsulate flavonoids and regulate the release of functional bioactive ingredients in the simulated human digestive conditions.


Safety and efficacy of Vecchietti vaginoplasty in vaginal agenesis: cohort study. Medellín, Colombia 2007-2012
To describe the Vecchietti vaginoplasty technique (VVT) in patients diagnosed with secondary vaginal agenesis and to analyze the safety and efficacy of this technique. Historical cohort of patients with vaginal agenesis secondary to Mayer- Rokitansky-Kuster-Hauser and androgen insensitivity syndromes, subjected to vaginoplasty using the Vecchietti technique at San Vicente Fundación University Hospital, a high complexity referral institution located in the city of Medellín, during the time period between 2007 and 2012. Patients with functional a vagina for intercourse were excluded. Sampling was consecutive. Sociodemographic, clinical, safety and efficacy variables were measured. Descriptive statistics were used. The main complaint was primary amenorrhea (69.2%). Associated malformations included right renal agenesis (15.4%) and skeletal malformations (15.4%). There was one intra-operative bladder perforation and, postoperatively, there were three (23.1%) minor complications. At 1-year follow-up, a functional vagina had been obtained in 84.6% of cases. Vecchietti vaginoplasty is a simple surgical technique resulting in satisfactory functional outcomes with only minor complications. Further studies with control groups are required in order to better assess the efficacy of the various techniques used for neovagina creation.


Sleep propensity at daytime as assessed by Multiple Sleep Latency Tests (MSLT) in patients with schizophrenia increases with clozapine and olanzapine.
Sleep propensity at daytime has not been investigated in untreated patients with schizophrenia. Furthermore, while the antipsychotics clozapine and olanzapine are considered to frequently cause 'sleepiness' or 'sedation', this has not been objectified yet. Therefore, 30 patients with schizophrenia were included in this randomized, double-blind study. Sleep propensity was assessed before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine using a Multiple Sleep Latency Test (MSLT); in the MSLT, sleep latencies of 5 nap opportunities of 20 min during daytime are averaged. In addition, the number of sleep onsets was recorded. Mean sleep latency in untreated schizophrenic patients was 16.2 ± 0.8 min at baseline. Both antipsychotics induced an increase of sleep propensity as indicated by a shortened sleep latency and more sleep onsets during the treatment period as compared to baseline. These effects were strongest in the morning. Four patients receiving clozapine and 3 patients receiving olanzapine reported subjective sleepiness, in all but one commencing in the first treatment week and persisting until study end. While the mean sleep latency during treatment was significantly shorter in these patients (12.3 ± 0.8 min) than in those without subjective sleepiness (14.9 ± 0.7 min), a short sleep latency was not necessarily associated with subjective sleepiness. In conclusion, mean sleep latency was >36% longer (i.e. sleep propensity was lower) in untreated patients with schizophrenia than in healthy subjects previously consistently reported. Furthermore, clozapine and olanzapine increased sleep propensity in schizophrenic patients. A minority of patients reported subjective sleepiness.


Therapy-resistant foreign body giant cell granuloma at the periapex of a root-filled human tooth.
Although the primary etiological factor of periapical lesions is microbial, there are other independent factors that can adversely affect the outcome of endodontic treatment. In this communication, we present morphological evidence in support of the role of a foreign body reaction of periapical tissue to root-filling materials. The specimen consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted after a decade of postendodontic follow-up. The biopsy was processed for correlated light and electron microscopy and was analyzed by various microtechniques. The unique feature of the lesion was the presence of vast numbers of large multinucleated cells and their cytoplasmic inclusion bodies. Morphologically, these multinucleated cells resembled foreign body giant cells. They contained characteristic birefringent cytoplasmic inclusions which on electron-probe X-ray microanalysis consistently revealed the presence of magnesium and silicon. The magnesium and silicon are presumably the remnants of a root-filling excess which protruded into the periapex and had been resorbed during the follow-up period. These observations strongly suggest that in the absence of microbial factors, root-filling materials which contain irritating substances can evoke a foreign body reaction at the periapex, leading to the development of asymptomatic periapical lesions that may remain refractory to endodontic therapy for long periods of time.


Prevalence and severity of liver disease in patients with b thalassemia major. A single-institution fifteen-year experience.
During the last years, liver disease has emerged as a major cause of mortality in patients with b thalassemia major (TM). In spite of its clinical relevance, TM-associated liver damage has been insufficiently characterized. We therefore retrospectively analyzed all TM patients of our Department who underwent liver biopsy since 1990.


Development of a heterogeneous phantom to measure range in clinical proton therapy beams.
In particle therapy, determination of range by measurement or calculation can be a significant source of uncertainty. This work investigates the development of a bespoke Range Length Phantom (RaLPh) to allow independent determination of proton range in tissue. This phantom is intended to be used as an audit device. RaLPh was designed to be compact and allows different configurations of tissue substitute slabs, to facilitate measurement of range using radiochromic film. Fourteen RaLPh configurations were tested, using two types of proton fluence optimised water substitutes, two types of bone substitute, and one lung substitute slabs. These were designed to mimic different complex tissue interfaces. Experiments were performed using a 115 MeV mono-energetic scanning proton beam to investigate the proton range for each configuration. Validation of the measured film ranges was performed via Monte Carlo simulations and ionisation chamber measurements. The phantom was then assessed as an audit device, by comparing film measurements with Treatment Planning System (TPS) predicted ranges. Varying the phantom slab configurations allowed for measurable range differences, and the best combinations of heterogeneous material gave agreement between film and Monte Carlo on average within 0.2% and on average within 0.3% of ionisation chamber measurements. Results against the TPS suggest a material density override is currently required to enable the phantom to be an audit device. This study found that a heterogeneous phantom with radiochromic film can provide range verification as part of a dedicated audit for clinical proton therapy beams.


Emergence of zoonotic Cryptosporidium parvum in China.
Zoonotic cryptosporidiosis is a major public health problem in industrialized nations; in those countries it is caused mainly by Cryptosporidium parvum IIa subtypes that are prevalent in dairy calves. Because of the short history of intensive animal farming in China, strains of C. parvum are found only on some dairy farms in this country and are the IId subtypes. However, the prevalence of C. parvum is increasing rapidly, with IIa subtypes recently detected in a few grazing animals, and both IIa and IId subtypes are emerging in humans. As animal farming intensifies, China may follow in the footsteps of industrialized nations where zoonotic cryptosporidiosis is rampant. One Health and biosecurity measures are urgently needed to slow down the dispersal of autochthonous IId subtypes and imported IIa subtypes.


Ligand recognition by vitamin D receptor: total alanine scanning mutational analysis of the residues lining the ligand binding pocket of vitamin D receptor.
We performed total alanine scanning mutational analysis (ASMA) of the residues lining the ligand binding pocket (LBP) of the human vitamin D receptor (hVDR) to investigate allosteric effects of ligands in the function of nuclear receptors (NRs). This was accomplished for the first time in the NR superfamily. The effects of ligand structure were also examined in this system (termed 2D-ASMA) using 8 representative VDR ligands. The results clearly revealed the role and importance of all amino acid residues lining the LBP and the relationships between ligand binding and transcriptional potency. 2D-ASMA indicated ligand-specific ligand-protein interactions, which are essential in determining the transactivation potency of the ligand. Taking the results as a whole, we suggest a ligand-mediated allosteric network, which allows transmission of information from ligands to the interfaces of the VDR in association with protein cofactors and was shown to be linked to a part of the network identified by statistical coupling analysis (SCA).


Down-regulation of Gi sub-types by prolonged incubation of adipocytes with an A1 adenosine receptor agonist.
We have reported previously that prolonged incubation of adipocytes with (-)-N6-phenylisopropyl adenosine (PIA) (an A1 adenosine receptor agonist) down-regulates A1 adenosine receptors. There was a concomitant decrease in pertussis toxin catalyzed ADP-ribosylation of a 41-kDa peptide thought to be the alpha-subunit of Gi. To determine whether this represents true down-regulation of the G-protein, and if so which of the three known forms of Gi are down-regulated, we have used antipeptide antisera specific for Gi alpha-subunits. Serum SG1 recognizes alpha i1 and -2, I1C recognizes only alpha i1, and I3B recognizes alpha i3. Rat adipocytes were maintained in primary culture for up to 7 days with 0-1000 nM PIA. Crude membrane preparations were analyzed by Western blots. There was almost complete loss of alpha i1 and -3, and about 50% loss of alpha i2 from PIA-treated cells. The loss of each alpha i was detectable after 24 h with 300 nM PIA and maximal by 4 days. After 4 days, down-regulation was detectable with 3 nM and maximal with 100 nM PIA. Antiserum BN2 demonstrated approximately 50% loss of G-protein beta-subunits in cells treated with 300 nM PIA for 4 days. When cells were incubated for 4 days with 300 nM PIA and then washed to remove PIA, alpha i1, -2, and -3 and beta-subunits returned to control levels within 5 days. Antiserum CS1 detected normal amounts of both the 43- and 47-kDa forms of Gs alpha in PIA-treated cells. We conclude that Gi alpha-subunits are down-regulated along with the adenosine receptor in rat adipocytes.


An analysis of the bovine genome by density gradient centrifugation: fractionation in Cs2SO4/3,6-bis(acetatomercurimethyl)dioxane density gradient.
The fractionation of calf thymus DNA by centrifugation in density gradients of Cs2SO4/BAMD, where BAMD = 3,6-bis(acetatomercurimethyl)dioxane, is described. A large-scale separation of (dG+dC)-rich DNA fractions has been obtained, allowing the relative amounts of minor and satellite components in the bovine genome to be precisely assessed.


Hepatitis C virus and intracellular antiviral response.
To establish successful infection in cells, it is essential for hepatitis C virus (HCV) to overcome intracellular antiviral responses. The host cell mechanism that fights against the virus culminates in the production of interferons (IFNs), IFN-stimulated genes (ISGs) and pro-inflammatory cytokines as well as the induction of autophagy and apoptosis. HCV has developed multiple means to disrupt the host signaling pathways that lead to these antiviral responses. HCV impedes signaling pathways initiated by pattern-recognition receptors (PRRs), usurps and uses the antiviral autophagic response to enhance its replication, alters mitochondrial dynamics and metabolism to prevent cell death and attenuate IFN response, and dysregulates inflammasomal response to cause IFN resistance and immune tolerance. These effects of HCV allow HCV to successful replicate and persist in its host cells.


Understanding childrens' health behaviour: the implications for health promotion for young people.
Understanding the causes and determinants of young people's health behaviour is central to the development of relevant and effective health promotion programmes. This paper traces the development of health education programmes in the past two decades, identifying the influence of a range of concepts and theories which emerged during that period. Drawing on results from a WHO Cross-National Study of children's health behaviour, the relationships between individual behaviours and a range of social and environmental influences are illustrated, together with the inter-relationship between individual behaviours as 'lifestyles'. The implications for health education programmes from the results are identified and special emphasis is given to the need to communicate effectively with young people through a range of networks and through the media, as well as through traditional school health education. The need to continue research into 'lifestyles' is also stressed.


An immunization method for generation of high affinity antisera against glucose transporters useful in immunohistochemistry.
Antipeptide antisera from unique amino acid sequences of proteins, predicted from their cDNA, are useful to study cellular distribution of these proteins, but such peptides often are poorly immunogenic. We describe a secondary immunization method with repeated intravenous administration of KLH-conjugated peptides to boost the immune response rapidly and transiently as high as 60-fold to peptides of low immunogenicity (glucose transporters, GLUT3 and GLUT4). Such antisera are suitable for immunocytochemistry with excellent anatomic detail. This method may be generally useful as it is reproducible and can yield progressive titer increases when repeated.


Adenosinergic regulation of the cardiovascular system in the red-eared slider Trachemys scripta.
Few studies have investigated adenosinergic regulation of the cardiovascular system in reptiles. The haemodynamic effect of a bolus intra-arterial adenosine injection (2.5 μM kg⁻¹) was investigated in nine anaesthetised red-eared sliders (Trachemys scripta). Adenosine caused a transient bradycardia, which was accompanied by systemic vasodilatation as evidenced by an increase in systemic flow and a decrease in systemic pressure. Meanwhile, pulmonary flow fell significantly. Both the bradycardia and increase in systemic conductance were significantly attenuated by theophylline (4 mg kg⁻¹), demonstrating an involvement of P₁ receptors. These results suggest that adenosine is likely to play a significant role in reptile cardiovascular physiology. In turtles specifically, adenosinergic regulation may be particularly relevant during periods of apnoea.


Femoral tunnel enlargement after anterior cruciate ligament reconstruction using RigidFix compared with extracortical fixation.
The aim of this study was to compare femoral tunnel enlargement after anterior cruciate ligament (ACL) reconstruction surgery using hamstring autograft tendons fixed by bioabsorbable femoral trans-tunnel pins with that in patients in which the graft was fixed with extracortical fixation. Forty-three patients were randomly selected from our database and included in the study. Femoral tunnel diameter was measured by computed tomography in 20 patients who underwent ACL reconstruction via anteromedial portal technique using autologous quadruple hamstrings, fixed with two bioabsorbable trans-tunnel pins, RigidFix, on the femoral side and compared with 23 patients in whom extracortical fixation, EndoButton CL, was used. The diameter of the femoral tunnel was measured at a distance of 5 mm from the tunnel entrance and at the largest diameter along the tunnel axis. Data were compared with the diameter of the drill used during surgery. Clinical evaluation was performed using the Lysholm score, IKDC subjective score and anterior knee laxity measurements. Femoral tunnel enlargement 5 mm from the entrance and at the largest diameter was greater in the RigidFix group than the EndoButton group. There were no significant differences between the two groups regarding age, gender, post-operative Lysholm score, IKDC subjective score or knee laxity measurements. The present study showed greater enlargement of the femoral bone tunnel when a bioabsorbable trans-tunnel pin system was used with the medial portal technique when compared to extracortical fixation. These findings confirm that femoral tunnel widening should be considered when RigidFix was used in ACL reconstruction by anteromedial portal technique. III.


Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure occurring during pregnancy. Its prevalence seems more frequent in Africa but its epidemiological, clinical and evolutionary particularities remain unknown. This study aimed to evaluate the epidemiological features and mortality risk factors of PPCM. We conducted a retrospective cross-sectional study over 38 months (January 2018 to March 2021) in 3 hospitals in the city of Douala(Cameroon). We included all patients with heart failure between the last month of pregnancy and 5 months after delivery without an identified cause. Were excluded, files not containing data on echocardiography, patients with heart failure without dilation or with LVEF≥ 45% and patients with a history of heart disease of known aetiology. Chi² tests and binary logistic regression were used for data analysis; the survival curve according to Kaplan Meier was drawn for the evolution. The threshold of significance was set at 0.05. A total of 2102 medical records of women with heart failure were searched. In these records, a total of 59 patients showed signs of peripartum heart failure and only 29 fulfilled the inclusion criteria. From a socio-demographic point of view, the average age was 29 ± 7 years and 51.7% of patients were over 30 years old. Among these patients, 79.3% of patients lived in urban areas and 10.3% of patients had a low socio-economic level. The hospital frequency of PPCM was 1.3%. Clinically, primiparous and pauciparous women were the most affected; the diagnosis was made after more than a month of progression in 65.5% of patients. Dyspnea was present in all patients. In addition, 89.7% of patients had a left ventricular end-diastolic diameter ≥ 62 m, 48.3 % had a left ventricular ejection fraction (LVEF) between 30% and 45%, and 51.7% had an LVEF < 30%. The associated mortality rate was 27.7%. The only prognostic factor independently associated with mortality was age < 30 years. The frequency of PPCM is relatively low in Cameroonian urban settings. Moreover, its diagnosis is generally delayed and it induces high mortality. Its occurrence in a woman under the age of 30 is a factor of poor prognosis.


One bone forearm with vascularized fibular graft. Clinical experience and literature review.
One-Bone-Forearm (OBF) is a procedure in which the proximal stump of the ulna is fixed to the distal stump of the radius. Historically, the indications for OBF have been represented by forearm instability due to trauma, infection, tumor resection, and congenital deformities with severe radius and ulna bone loss. When major bone loss prevents direct fixation between ulna and radius a Vascularized Fibular Bone Graft (VFBG) may allow forearm bone reconstruction and fixation. In this study we report our clinical experience in 4 cases of OBF with VFBG performed in 3 patients. Compared to standard OBF technique with direct osteodesis, OBF with VFBG showed similar clinical results and high rate of healing even in case of bone infection. Moreover, composite osteocutaneous VFBG might concurrently allow to treat local soft tissue defects.