HLA-G, pre-eclampsia, immunity and vascular events.
Pre-eclampsia, one of the main complications in pregnancy, is characterised by shallow cytotrophoblast invasion of decidua as well as by vascular endothelial cell dysfunction, leading to a poor perfusion of placenta. A striking feature of pre-eclamptic pregnancies is that expression of HLA-G protein is reduced in term placentas compared with normal pregnancy. How such HLA-G deficient expression may be related to the pre-eclamptic pathology is unknown. Here, we review the major structural characteristics of HLA-G and some of its functions that have been recently characterised. Soluble HLA-G1 isoform down-regulates both CD8(+) and CD4(+) T cell reactivity. HLA-G also modulates innate immunity by binding to several NK and/or decidual receptors, inducing particular cytokine secretion. HLA-G was shown to be less susceptible to human cytomegalovirus-derived US protein down-modulation. Finally, soluble HLA-G1 down-regulates endothelial cell proliferation and migration. In view of these different HLA-G properties, we will briefly discuss how defective HLA-G function may contribute to the low trophoblast invasion and vascular abnormalities observed in pre-eclamptic placentas.


[Evaluation of the therapeutic efficacy and tolerance of a new thiamine compound (benzoyloxymethylthiamine) in the treatment of postoperative pain symptomatology in odontostomatological surgery].
The therapeutic effectiveness of benzoyloxymethyl-thiamin in controlling post-operative pain in odontostomatological surgery has been examined. The double blind study used a placebo and concerned 100 patients subjected to avulsion of the third molar in dysodontiasis on an out-patient basis. The results point to the effectiveness of benzoyloxymethyl-thiamin in the symptomatic treatment of post-operative pain symptomatology both as regards its duration and intensity; the drug also proved to be very well tolerated and its administration was not accompanied by any unwanted side-effects.


Pathologic Response to Preoperative Therapy as a Novel Prognosticator for Ampullary and Duodenal Adenocarcinoma.
The prognostic impact of pathologic response to preoperative therapy on patients with duodenal adenocarcinoma (DA) and ampullary adenocarcinoma (AMPA) has not been established. A retrospective review of 266 patients who underwent curative resection for DA (n = 97) or AMPA (n = 169) during 1993-2015 was performed. For patients who underwent preoperative therapy, the pathologic response was systematically evaluated and classified as major (0-49% of viable residual tumor cells) or minor (≥ 50% of viable residual tumor cells). Uni- and multivariable analyses were performed to identify predictors of pathologic response and disease-specific survival (DSS). For the 79 patients treated with preoperative therapy (DA: n = 34; AMPA: n = 45), concomitant use of radiation (80%, 67/79) was the sole independent predictor of major pathologic response (odds ratio [OR] 8.17; 95% confidence interval [CI] 1.85-58.2; P = 0.005). The patients with major pathologic response had a better 5-year DSS rate than the patients with minor pathologic response (DA: 65 vs 25%; P = 0.028; AMPA: 85 vs 43%; P = 0.016). In the multivariable analysis of DSS for the 79 patients who underwent preoperative therapy, major pathologic response was the sole predictor of improved DSS (hazard ratio [HR] 2.88; 95% CI 1.41-5.98; P = 0.004). In the multivariable analysis of DSS for the entire cohort, pathologic stage 2 or lower was the sole predictor of better DSS. The major pathologic response to preoperative therapy predicted improved DSS after resection of DA and AMPA and might represent a new prognosticator after resection of DA and AMPA.


Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica.
The aim of the present study was to evaluate the effect of release rate from ordered mesoporous silica materials on the rate and extent of absorption of the poorly soluble drug fenofibrate. Three ordered mesoporous silica materials with different pore diameter (7.3 nm, 4.4 nm and 2.7 nm) were synthesized and loaded with fenofibrate via impregnation. Release experiments were conducted under sink conditions and under supersaturating conditions in biorelevant media, simulating the fasted and the fed state. Subsequently, all silica-based formulations were evaluated in vivo (rat model). The release experiments under sink conditions indicated a clear increase in release rate with increasing pore size. However, under supersaturating conditions (FaSSIF), the, pharmaceutical performance (in terms of both the degree and duration of supersaturation), increased with decreasing pore size. The same trend was observed in vivo (fasted state): the area under the plasma concentration-time profile amounted to 102 ± 34 μMh, 86 ± 19 μMh and 20 ± 13 μMh for the materials with pore diameter of 2.7 nm, 4.4 nm and 7.3 nm, respectively. The results of this, study demonstrate that a decrease in drug release rate - and thus, a decrease of the rate at which supersaturation is created - is beneficial to the absorption of fenofibrate.


NPHS2 mutations.
To uncover the frequency and the spectrum of NPHS2 mutations in Egyptian children with non familial steroid-resistant nephrotic syndrome (SRNS). Sixteen patients were screened by PCR-single-strand conformation polymorphism analysis of NPHS2 gene followed by direct sequencing. NPHS2 mutations were evident in four patients (25%) who were bearing four novel mutations including two frame shift mutations (R238fs and P45fs) and two missense mutations (I136L and F216Y). There were no phenotypic or histological characteristics of patients bearing NPHS2 mutations, apart from the earlier onset of the disease, compared to those who were not bearing mutations. NPHS2 mutations are prevalent in Egyptian children with non-familial SRNS and this may in part explain the less favorable prognosis reported in these patients.


Needle-free jet injection of small doses of Japanese encephalitis DNA and inactivated vaccine mixture induces neutralizing antibodies in miniature pigs and protects against fetal death and mummification in pregnant sows.
Japanese encephalitis (JE) virus causes abortion and stillbirth in swine, and encephalitis in humans and horses. We have previously reported that immunogenicity of a DNA vaccine against JE was synergistically enhanced in mice by co-immunization with a commercial inactivated JE vaccine (JEVAX) under a needle-free injection system. Here, we found that this immunization strategy was also effective in miniature pigs. Because of the synergism, miniature pigs immunized twice with a mixture of 10 μg of DNA and a 1/100 dose of JEVAX developed a high neutralizing antibody titer (1:190 at 90% plaque reduction assay). Even using 1 μg of DNA, 3 of 4 pigs developed neutralizing antibodies. Following challenge, all miniature pigs with detectable neutralizing antibodies were protected against viremia. Pregnant sows inoculated with 10 or 1 μg of DNA mixed with JEVAX (1/100 dose) developed antibody titers of 1:40-1:320. Following challenge, fetal death and mummification were protected against in DNA/JEVAX-immunized sows.


Ionothermal Synthesis of Imide-Linked Covalent Organic Frameworks.
Covalent organic frameworks (COFs) are an extensively studied class of porous materials, which distinguish themselves from other porous polymers in their crystallinity and high degree of modularity, enabling a wide range of applications. COFs are most commonly synthesized solvothermally, which is often a time-consuming process and restricted to well-soluble precursor molecules. Synthesis of polyimide-linked COFs (PI-COFs) is further complicated by the poor reversibility of the ring-closing reaction under solvothermal conditions. Herein, we report the ionothermal synthesis of crystalline and porous PI-COFs in zinc chloride and eutectic salt mixtures. This synthesis does not require soluble precursors and the reaction time is significantly reduced as compared to standard solvothermal synthesis methods. In addition to applying the synthesis to previously reported imide COFs, a new perylene-based COF was also synthesized, which could not be obtained by the classical solvothermal route. In situ high-temperature XRPD analysis hints to the formation of precursor-salt adducts as crystalline intermediates, which then react with each other to form the COF.


Efficacy of rodenticide baits with decreased concentrations of brodifacoum: Validation of the impact of the new EU anticoagulant regulation.
Anticoagulants are the most frequently used rodenticides at the global scale. Because of their persistency, bioaccumulation and potential for secondary intoxication, they have faced increasing legislative regulations. Recently, the European Union Regulation (EU) 2016/1179 resulted in the production and application of rodenticides with nearly half dose (<30 ppm) of anticoagulants. However, published data on the biological efficacy of rodenticides with decreased doses are scarce in the EU. Therefore, this work compared the efficacy of the original high-dose (50 ppm) and new low-dose (25 ppm) brodifacoum-based baits in the offspring of wild-caught house mice (Mus musculus L.). In the no-choice laboratory feeding tests, 100% animals died in all treated groups and 0% died in the control groups. The achieved time to death did not differ between the original and low-dose baits across both types of feeding trials/regimes. The low-dose baits (25 ppm) were consequently tested under field conditions in two populations showing 95.7% and 99.8% efficacy. The obtained results highlighted the good efficacy of the new baits based on low-dose brodifacoum in non-resistant mouse populations. However, further validation is required regarding the remaining anticoagulant compounds and resistant rodent populations.


Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case-control study.
Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.


[Lengthening temporalis myoplasty: A new approach to facial rehabilitation with the "mirror-effect" method].
Peripheral facial paralysis often reveals two conditions that are hard to control: labial occlusion and palpebral closure. Today, there are efforts to go beyond the sole use of muscle stimulation techniques, and attention is being given to cerebral plasticity stimulation? This implies using the facial nerves' efferent pathway as the afferent pathway in rehabilitation. This technique could further help limit the two recalcitrant problems, above. We matched two groups of patients who underwent surgery for peripheral facial paralysis by lengthening the temporalis myoplasty (LTM). LTM is one of the best ways to examine cerebral plasticity. The trigeminal nerve is a mixed nerve and is both motor and sensory. After a LTM, patients have to use the trigeminal nerve differently, as it now has a direct role in generating the smile. The LTM approach, using the efferent pathway, therefore, creates a challenge for the brain. The two groups followed separate therapies called "classical" and "mirror-effect". The "mirror-effect" method gave a more precise orientation of the patient's cerebral plasticity than did the classical rehabilitation. The method develops two axes: voluntary movements patients need to control their temporal smile; and spontaneous movements needed for facial expressions. Work on voluntary movements is done before a "digital mirror", using an identical doubled hemiface, providing the patient with a fake copy of his face and, thus, a 7 "mirror-effect". The spontaneous movements work is based on what we call the "Therapy of Motor Emotions". The method presented here is used to treat facial paralysis (Bell's Palsies type), whether requiring surgery or not. Importantly, the facial nerve, like the trigeminal nerve above, is also a mixed nerve and is stimulated through the efferent pathway in the same manner.


Enhancing insecticidal efficacy of Bacillus thuringiensis Cry1Ab through pH-sensitive encapsulation.
Nanotechnology is a promising way to enhance the stability of Bacillus thuringiensis (Bt) insecticidal proteins under environmental conditions. In this work, two emulsions were prepared through the Pickering emulsion technique, stabilized by Cu2+-SQDs/S-CN nanocomposites and by GO nanosheets. In addition, a pH-sensitive polymer was incorporated into these emulsions, allowing the Bt protein, Cry1Ab, to be released in an alkaline pH environment, as it occurs in the lepidopteran pests' gut. The effectiveness of these two nanomaterials in protecting Cry1Ab from degradation, and therefore enhancing its pesticidal activity, was assessed by exposing samples of the purified unprotected protein and encapsulated protein to high-intensity UV light and 40°C temperature treatments. The UV treatment results were evaluated using SDS-PAGE analysis and pointed out that Cry1Ab could be structurally protected by the emulsions. The bioassays with first instar larvae of the lepidopteran pest Ostrinia nubilalis confirm the nanomaterial protection to UV and temperature treatments, i.e., decreasing about half the degradation rate and increasing up to 12-fold the residual activity after UV treatment. Our results indicate that encapsulation could be an effective strategy to improve the effectiveness of Cry1Ab under environmental conditions. KEY POINTS: • Pickering emulsions are effective for solubilized Cry1Ab encapsulation. • Structural and toxicity Cry1Ab properties are enhanced by pH-sensitive encapsulation. • Cu2+-SQDs/S-CN and GO nanomaterials improve the efficacy of Bt insecticides.


Indication, selection of patients and timing for pancreatic transplantation.
For more than 20 years pancreas transplantation has been advocated as a therapeutic modality in patients with insulin-dependent diabetes mellitus. When successful, this procedure is the only method for attaining long-term normoglycaemia in diabetic recipients. However, because of the potential morbidity and mortality, pancreas transplantation should be restricted to diabetic patients in whom the complications of the diabetic state are more serious than those of surgery and chronic immunosuppression. Currently three recipient categories have been identified in which pancreas transplantation would seem justifiable. The first includes diabetic patients with end-stage nephropathy who are already obligated to life-long immunosuppressive therapy because of the kidney replacement. In this recipient category the main benefit of receiving a pancreas transplant in addition to a kidney is that the quality of life is markedly improved. In addition, it seems that a functioning pancreas transplant prevents the recurrence of diabetic nephropathy in the simultaneously transplanted kidney. Since the success rate with combined pancreas-kidney transplantations is approaching that of renal transplantation alone, there is little controversy about performing the combined procedure in diabetic uraemic patients. However, if the main objective of pancreas transplantation, namely to prevent the late diabetic microvascular complications, were to be fulfilled this intervention would have to be performed earlier in the course of the disease. Therefore, single pancreatic transplantations have recently been conducted in diabetic patients with early signs of clinical nephropathy which, currently, is the most powerful predictor of susceptibility to detrimental diabetic complications. Preliminary findings indicate that, in this second recipient category, single pancreatic transplantation and subsequent euglycaemia may prevent the progression of diabetic neuropathy and nephropathy; with regard to diabetic retinopathy the results remain obscure.(ABSTRACT TRUNCATED AT 250 WORDS)


Understanding embryonic development for cell-based therapies of intervertebral disc degeneration: Toward an effort to treat disc degeneration subphenotypes.
Chronic low back and neck pain are associated with intervertebral disc degeneration and are major contributors to the global burden of disability. New evidence now suggests that disc degeneration comprises a spectrum of subphenotypes influenced by genetic background, age, and environmental factors, which may be contributing to the mixed outcomes seen in clinical trials of cell-based therapies that aim to treat disc degeneration. This problem is further compounded by the fact that disc degeneration and aging coincide with an exhaustion of endogenous progenitor cells, imposing limitations on the regenerative capacity of the disc. At the bench-side, current work is focused on applying our knowledge of embryonic disc development to direct and refine differentiation of adult and human-induced pluripotent stem cells into notochord-like and nucleus pulposus-like cells for use in novel cell-based therapies. Accordingly, this review presents the salient features of intervertebral disc development, post-natal maintenance, and regeneration, with emphasis on recent advancements. We also discuss how a stratified approach can be undertaken for the development of future cell-based therapies to bring emerging subphenotypes into consideration.


Abalone water-soluble matrix for self-healing biomineralization of tooth defects.
Enamel cannot heal by itself if damaged. Hydroxyapatite (HAP) is main component of human enamel. Formation of enamel-like materials for healing enamel defects remains a challenge. In this paper, we successfully isolated the abalone water-soluble matrix (AWSM) with 1.53wt% the abalone water-soluble protein (AWSPro) and 2.04wt% the abalone water-soluble polysaccharide (AWSPs) from abandoned abalone shell, and self-healing biomineralization of tooth defects was successfully achieved in vitro. Based on X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), hot field emission scanning electron microscopy (HFESEM) and energy dispersive spectrometer (EDS) analysis, the results showed that the AWSM can efficiently induce remineralization of HAP. The enamel-like HAP was successfully achieved onto etched enamel's surface due to the presence of the AWSM. Moreover, the remineralized effect of eroded enamel was growing with the increase of the AWSM. This study provides a solution to the resource waste and environmental pollution caused by abandoned abalone shell, and we provides a new method for self-healing remineralization of enamel defects by AWSM and develops a novel dental material for potential clinical dentistry application.


Detrusor myectomy: long-term results with a minimum follow-up of 2 years.
To assess the long-term results of detrusor myectomy, which has obvious theoretical advantages over enterocystoplasty for refractory detrusor overactivity (DO), and for which the early results have been encouraging. The medical records were reviewed of 30 consecutive patients (median age 33 years, range 10-62) who had a detrusor myectomy between November 1992 and April 2002 in our unit. Twenty-four patients (80%) had idiopathic DO (six males and 18 females) and six (20%) had neurogenic DO (four males and two females). The median (range) follow-up was 79 (28-142) months. All patients were confirmed to have DO on urodynamics before surgery and 26 (87%) had urodynamics afterward. Nineteen (79%) of those with idiopathic DO and two with neurogenic DO showed a continued overall improvement. The cystometric capacity improved in 80% of patients after surgery, whilst the detrusor pressure at maximum flow and the bladder contractility index decreased in 60% and 78% of the patients, respectively. Ten patients (45%) had to start clean intermittent self-catheterization after surgery. Detrusor myectomy is successful in approximately 80% of patients with idiopathic DO, although detrusor contractility is affected in most and almost half of the patients required clean intermittent self-catheterization afterward. This procedure should be offered as an alternative to enterocystoplasty as it is less morbid and does not preclude subsequent surgery if required. However, further evaluation of this technique is required in neuropathic patients.


Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas.
Perfluorooctanoic acid (PFOA) is used in the manufacture of many industrial and commercial products. PFOA does not readily decompose in the environment, and is biologically persistent. Human epidemiologic and animal studies suggest that PFOA exposure elicits adverse effects on the pancreas. While multiple animal studies have examined PFOA-mediated toxicity in the liver, little is known about the potential adverse effects of PFOA on the pancreas. To address this, we treated C57Bl/6 mice with vehicle, or PFOA at doses of 0.5, 2.5 or 5.0 mg/kg BW/day for 7 days. Significant accumulation of PFOA was found in the serum, liver and pancreas of PFOA-treated animals. Histopathologic examination of the pancreas revealed focal ductal hyperplasia in mice treated with 2.5 and 5.0 mg/kg BW/day PFOA, while inflammation was observed only in the high dose group. Elevated serum levels of amylase and lipase were observed in the 2.5 mg/kg BW/day PFOA treatment group. In addition, PFOA exposure resulted in a dose-dependent increase in the level of the lipid peroxidation product 8-iso-PGF2α and induction of the antioxidant response genes Sod1, Sod2, Gpx2 and Nqo1. Our findings provide additional evidence that the pancreas is a target organ for PFOA-mediated toxicity and suggest that oxidative stress may be a mechanism through which PFOA induces histopathological changes in the pancreas.


Development of an oral mucosal irritation test using a three-dimensional human buccal oral mucosal model.
The oral mucosa can become irritated by oral care products and lip cosmetics. Therefore, it is important to determine the irritation potential of their ingredients and products during safety evaluations. We developed a method for oral mucosal irritation test using EpiOral, which is a three-dimensional cultured model. Exposure of sodium lauryl sulphate (SLS) to EpiOral showed a dose-dependent decrease in cell viability. Under 120 min exposure conditions, SLS irritation was detected when 60% cell viability was set as a criterion. Evaluation of the irritancy of SLS and four other raw materials used in oral products at three laboratories under the above conditions confirmed good transferability of the test. Focused on the similarity of the oral and eye mucous, 32 chemicals categorised by the UN-GHS eye-irritation classification were evaluated to ensure the reliability of our criteria at these laboratories. The concordance rate between the UN-GHS classification and our test results was 100% for irritants and 60% for non-irritants. The good intra-laboratory reproducibility of our test was confirmed from the evaluation results of negative and positive controls, and the good inter-laboratory reproducibility was confirmed from the results of 32 chemicals. These findings showed that oral mucosal irritation can be evaluated using EpiOral.


Organic causes of dyspepsia, and discriminating functional from organic dyspepsia.
A wide variety of disorders affecting the upper gastrointestinal tract, as well as systemic disorders, are associated with symptoms of dyspepsia. The more important of these conditions are considered in this chapter, with particular reference to their symptom patterns on presentation. The differentiation, on clinical grounds, between these organic causes of dyspepsia and functional dyspepsia remains an important area of research. Those aspects of the history and physical examination most relevant to this distinction are also considered.


Newcastle disease virus infection triggers HMGB1 release to promote the inflammatory response.
High mobility group box 1 (HMGB1) is a key member of the "danger associated molecular patterns" (DAMPs) which plays important roles in systemic inflammation and has a pathogenic role in infectious diseases like viral or bacterial infections. Newcastle disease virus (NDV) infection is proved to cause intense inflammatory responses that result in excessive cellular apoptosis and tissue damage, but the function of HMGB1 in NDV-induced cytokine storm has not been elucidated. Here, we report that HMGB1 is a significant inflammation factor in NDV infection. HMGB1 is widely distributed in chicken tissues, and the secretion of it was induced by NDV infection both in DF-1 and A549 cells. Moreover, inhibiting the secretion of HMGB1, NDV replication was not significantly reduced, but it is involved in NDV-induced NF-κB activation and the inflammatory response. Further investigation showed that HMGB1 promotes inflammatory cytokine production through the RAGR, TLR2, and TLR4 receptors. HMGB1-RAGE interaction also takes parts in activation of ERK1/2 and JNK induced by NDV infection. Neutralizing HMGB1 in vivo, chicken viability was increased. Pathological changes and inflammatory cytokines expression were reduced under NDV infection, which further confirmed the pathogenic roles of HMGB1 in inflammatory responses. Thus, our findings show that HMGB1 contributes to the inflammatory cytokine storm induced by NDV infection, which played a critical role in viral pathogenesis.


Melatonin alleviates cadmium-induced nonalcoholic fatty liver disease in ducks by alleviating autophagic flow arrest via PPAR-α and reducing oxidative stress.
Cadmium (Cd) is an important environmental pollutant that causes liver damage and induces nonalcoholic fatty liver disease (NAFLD). NAFLD is a fat accumulation disease and has significant effects on the body. Melatonin (Mel) is an endogenous protective molecule with antioxidant, anti-inflammatory, antiobesity, and antiaging effects. However, whether Mel can alleviate Cd-induced NAFLD and its mechanism remains unclear. First, in vivo, we found that Mel maintained mitochondrial structure and function, inhibited oxidative stress, and reduced Cd-induced liver injury. In addition, Mel alleviated lipid accumulation in the liver induced by Cd. In this process, Mel inhibits fatty acid production and promotes fatty acid oxidation. Interestingly, Mel regulated PPAR-α expression and alleviated Cd-induced autophagy blockade. In vitro model, the oil Red O staining, and WB results showed that Mel alleviated Cd-induced lipid accumulation. In addition, RAPA was used to activate autophagy to alleviate Cd-induced lipid accumulation, and TG was used to block autophagy flux to aggravate Cd-induced autophagy accumulation. After knocking down PPAR-α, the autophagosome fusion with lysosomes, and autophagic flux was inhibited and increased Cd-induced lipid accumulation. Mel alleviates mitochondrial damage and oxidative stress, and attenuates Cd-induced NAFLD by restoring the expression of PPAR-α and restoring autophagy flux.


Organ-specific analysis of the anaerobic primary metabolism in rice and wheat seedlings. I: Dark ethanol production is dominated by the shoots.
During anaerobiosis in darkness the main route for ATP production in plants is through glycolysis in combination with fermentation. We compared the organ-specific anaerobic fermentation of flooding-tolerant rice (Oryza sativa) and sensitive wheat (Triticum aestivum) seedlings. A sensitive laser-based photoacoustic trace gas detection system was used to monitor emission of ethanol and acetaldehyde by roots and shoots of intact seedlings. Dark-incubated rice seedlings released 3 times more acetaldehyde and 14 times more ethanol than wheat seedlings during anaerobiosis. Ninety percent of acetaldehyde originated from shoots of both species. In comparison to wheat shoots, the high ethanol production of rice shoots correlated with larger amounts of soluble carbohydrates, and higher activities of fermentative enzymes. After 24 h of anaerobiosis in darkness rice shoots still contained 30% of aerated ATP level, which enabled seedlings to survive this period. In contrast, ATP content declined almost to zero in wheat shoots and roots, which were irreversibly damaged after a 24-h anaerobic period. When plants were anaerobically and dark incubated for 4 h and subsequently transferred back to aeration, shoots showed a transient peak of acetaldehyde release indicating prompt re-oxidation of ethanol. Post-anoxic acetaldehyde production was lower in rice seedlings than in wheat. This observation accounts for a more effective acetaldehyde detoxification system in rice. Compared to wheat the greater tolerance of rice seedlings to transient anaerobic periods is explained by a faster fermentation rate of their shoots allowing a sufficient ATP production and an efficient suppression of toxic acetaldehyde formation in the early re-aeration period.


Use and efficacy of mouthwashes in elderly patients: A systematic review of randomized clinical trials.
A higher prevalence of oral problems has been observed in the elderly population. One of the treatment options for some of these pathologies is the administration of mouthwashes combined with mechanical removal techniques. Besides, each type of oral rinse treats certain oral diseases, and it should be selected for each specific situation. To determine the use and efficacy of mouthwashes in the elderly as a treatment for various pathologies, to indicate the most common kinds of mouth-rinses used, the diseases treated with them, their efficacy in each treatment, and their effectiveness when they are combined with other treatments. The review has been carried out following the PRISMA 2020 Statement. Individualized bibliographic searches were performed in five databases. Randomized clinical trials are included in patients over 60 years old where mouthwashes were administered to treat or prevent specific diseases. The PICO question aimed to assess what type of mouthwashes elderly patients use, what they use them for, and their efficacy. Study selection, data extraction, and quality analysis were achieved using the RoB-2 guide. Thirteen articles were chosen to perform the qualitative analysis. The bibliometric analysis was carried out. We have eleven randomized controlled clinical trials and two uncontrolled. The mouthwash more used was chlorhexidine, followed by essential oils and fluorides. The most studied pathologies were a periodontal disease, caries, candidiasis, denture stomatitis, and xerostomia. Chlorhexidine used weekly is effective as antiplaque and antigingivitis. Fluorides effectively prevent and reverse caries; nystatin and essential oils to treat candidiasis; and pilocarpine rinse to manage xerostomia. The included studies show that mouthwashes are widely extended in the elderly population, and each sort is specifically designed for treating a particular condition.


Efficacy of bronchodilators administered by nebulizers versus spacer devices in infants with acute wheezing.
The aim of this study was to compare the response of infants with acute wheezing to treatments with inhaled terbutaline when administered by nebulizer or by metered-dose inhaler and spacer device (MDI-spacer). Thirty-four infants between the ages of 1 and 24 months who were seen in our emergency department for acute wheezing were studied in a double-blind, randomized trial. The participants received two treatments of terbutaline at 20-min intervals, either by a nebulizer (2 mg/dose in 2.8 mL of 0.9% saline solution) or by an MDI-spacer device (0.5 mg/dose). The outcome measure was a clinical score, based on respiratory rate, degree of wheezing, retractions, degree of cyanosis, color, and pulse oximetry data measured before treatment, 20 min after the first treatment, and again 20 min after the second treatment. There was no difference in the rate of improvement in the clinical score between infants who received terbutaline by nebulizer and those who received it by MDI-spacer. We conclude that MDI-spacers and nebulizers are equally effective means of delivering beta-2 agonists to infants and small children with acute wheezing.


Acute glucocorticoid effects on response inhibition in borderline personality disorder.
Growing evidence suggests inhibition dysfunctions in borderline personality disorder (BPD). Moreover, abnormalities in hypothalamic-pituitary-adrenal (HPA) axis functioning have also been found in BPD patients. In healthy individuals, response inhibition has been sensitive to acute stress, and previous research indicates that effects mediated by the HPA axis become particularly apparent when emotional stimuli are processed. This study aimed to explore the influence of acute hydrocortisone administration on response inhibition of emotional stimuli in BPD patients compared to healthy control participants. After a single administration of 10mg hydrocortisone or placebo, 32 female BPD patients and 32 healthy female participants performed an adapted emotional go/no-go paradigm to assess response inhibition for emotional face stimuli in a cross-over study. Acute cortisol elevations decreased the reaction times to target stimuli in both BPD patients and healthy controls. Patients and controls did not differ in task performance; however, BPD patients with comorbid posttraumatic stress disorder (PTSD) displayed longer reaction times than patients without PTSD. In contrast, the occurrence of comorbid eating disorder had no significant impact on go/no-go performance. No significant interaction effect between the treatment condition and the emotional valence of the face stimuli was found. Acute hydrocortisone administration enhances response inhibition of face stimuli in BPD patients and healthy controls, regardless of their emotional valence. Our results agree with the suggestion that moderate cortisol enhancement increases the inhibition of task-irrelevant distracters.


Practice of Health Care Governance among South Wollo Department Heads and Managers of Public Health Institutions, Northeast Ethiopia.
Governance in health care generally means strengthening leadership and governance functions, improving systems, and having both central and local governments jointly take responsibility for overall health system performance. More than half of the world's population has expressed distrust of state institutions including the health sector. Ethiopia, like other African countries, faces many challenges in the process of good governance building. The aim of this study was to assess the practices health care governance in the South Wollo Zone health sectors, Northeast Ethiopia. A facility-based cross-sectional study design was conducted in the South Wollo from 15 May to 15 June 2021. A simple random sampling technique was used, and the data were collected using a structured survey. The data were entered into Epi data version 4.6 for cleaning and exported to SPSS v.25 for further analysis. We performed binary and multivariable logistic regression analysis to identify factors of governance practices. Variables with p values less than 0.05 during multivariable logistic regression analysis were declared statistically significant. A 96.75% (387) of the study participants completed the study questionnaires. Out of these, 37.98% (95% confidence interval: 33.1%, 42.9%) have been found practicing good governance in the health sector. Having had training (adjusted odds ratio = 7.92, 95% confidence interval: 4.04, 15.51), having job descriptions (adjusted odds ratio = 2.05, 95% confidence interval: 1.03, 4.09), opportunity to share with peers (adjusted odds ratio = 6.64, 95% confidence interval: 3.02, 14.62), political interference (adjusted odds ratio = 0.40, 95% confidence interval: 0.22, 0.71), and age < 25 years (adjusted odds ratio = 0.13, 95% confidence interval: 0.02, 0.77) were found to have a statistically significant association with the governance practice of managers. The overall practice of governance was found poor in light of the national and World Health Organization standards for health sector Governance. Having had training, having job descriptions and the opportunity to share with peers significantly increased the odds of good governance while political interference and young age significantly decreased the odds of good governance. Managers could implement training, write job descriptions, and encourage sharing with peers to improve governance.


The Olfactory Mucosa of Butter Catfish Clupisoma garua (Siluriformes, Ailiidae): An Ultrastructural Study.
The olfactory system is one of the most important chemosensory systems for teleosts. The olfactory epithelium of freshwater catfish Clupisoma garua (Siluriformes, Ailiidae) was studied by the aid of light microscopy and transmission electron microscopy. Mature sex-independent fish species were collected from Hooghly River, a distributary channel of river Ganga. Following routine procedure of ultrastructural techniques, different sensory and nonsensory cells lining the olfactory epithelium were described. The lamella contained two epithelia, with a central core sandwiched in between. Based on distribution pattern and structural characteristics of cell, each olfactory lamella was differentiated into sensory and nonsensory epithelium. The smaller sensory epithelium contained morphologically distinct ciliated, microvillous, and rod receptor cells, distinguished based on staining patterns, characteristic length, and architecture of their dendritic terminals. The nonsensory epithelium comprising the greater surface area was made up of labyrinth cells, mast cells, supporting cells, ciliated nonsensory cells, and basal cells. The cilia furnished a characteristic 9 + 2 microtubule arrangement. The functional significance of various cells on the olfactory epithelium was correlated with behavior of the fish concerned.


Accumulation of polybrominated diphenyl ethers (PBDEs) in mudsnails (Cipangopaludina cahayensis) did not increase with age.
In this study, we examined concentrations of polybrominated diphenyl ethers (PBDEs) in mudsnails (Cipangopaludina cahayensis) and sediment samples from an electronic waste recycling area to investigate the correlation between PBDE accumulation and age. The results showed that PBDE accumulation did not increase with age, suggesting a dynamic balance between the uptake, depuration and biotransformation of PBDEs relative to growth dilution in mudsnails. We infer that this phenomenon is associated with low absorption efficiencies, rapid depuration rates and high biotransformation rates of PBDEs. BDE-209 contributed only up to about 5 %, whereas BDE-209 was the dominant congener and contributed up to 90 % of the total PBDEs in surface sediments. The difference in PBDE congener pattern between mudsnails and sediments showed a low bioaccumulation potential for these compounds in mudsnails.


Early postoperative complications in patients with Crohn's disease given and not given preoperative total parenteral nutrition.
The effect of preoperative total parenteral nutrition (TPN) on the rate of early (within 30 days) postoperative complications in patients with moderate to severe Crohn's disease (CD) was examined. A series of 15 consecutive patients with CD (mean CD activity index score, 270) given preoperative TPN for 18-90 days (mean, 46 days) and undergoing bowel resection and primary anastomosis was compared with matching controls (105 patients) consecutively selected from all CD patients operated in Stockholm County during a preceding 20-year period without preoperative TPN. During the preoperative TPN, all the patients studied displayed clinical remission of CD as reflected in improvement in their general well-being, relief of abdominal pain, and abatement of fever and diarrhea. There was no significant early postoperative complication in the TPN-treated group, whereas there were 29 patients with early postoperative complications in the control group, which means a significantly higher rate of postoperative complications when preoperative TPN was not provided. During the preoperative TPN, some crucial variables increased such as the body weight, the serum concentrations of albumin and triiodothyronine reflecting improved nutritional state, whereas the serum concentration of haptoglobin and the white cell count decreased reflecting decreased inflammatory activity. This study shows that preoperative TPN for at least 18 days may be recommended to be given to patients with moderate to severe CD until clinical remission is achieved in order to minimize the risk of early postoperative complications.


Enhanced intestinal stability and pH sensitive release of quercetin in GIT through gellan gum hydrogels.
The objective of the work was to improve the intestinal stability and pH sensitive release of quercetin in the gastrointestinal tract. To achieve this aim, novel quercetin loaded pH sensitive hydrogel beads of gellan gum were developed through an ionic cross-linking technique using calcium chloride (CaCl2) as cross-linking agents. Field emission scanning electron microscopy (FESEM) was used to characterize the morphological appearance of the prepared hydrogel beads. Drug-polymer and drug-CaCl2 interaction were studied by using infrared spectroscopy. The important finding of the study was the formation of stable hydrogel beads at a very low concentration of CaCl2 (0.3 % w/v). There was a drug polymer interaction in addition to polymer and CaCl2 interaction that is confirmed by infrared spectroscopy. All the formulation shows good entrapment efficiencies within the range of 58.56-93.71 %. The prepared beads exhibited a pH responsive swelling behavior with maximum swelling at the simulated intestinal fluid (pH 7.4) (SIF). Hydrogel beads also showed a pH responsive release behavior and sustained release of drug at SIF. Moreover, the intestinal stability of quercetin was improved when encapsulated in gellan gum hydrogel beads in comparison to the solution containing quercetin.


Researchers' experiences, positive and negative, in integrative landscape projects.
Integrative (interdisciplinary and transdisciplinary) landscape research projects are becoming increasingly common. As a result, researchers are spending a larger proportion of their professional careers doing integrative work, participating in shifting interdisciplinary teams, and cooperating directly with non-academic participants. Despite the growing importance of integrative research, few studies have investigated researchers' experiences in these projects. How do researchers perceive the outcomes of integrative projects, or career effects? Do they view the projects generally as successes or failures? This study analyses researchers' experiences in integrative landscape studies and investigates what factors shape these experiences. The data stems from 19 semi-structured qualitative interviews and a Web-based survey among 207 participants in integrative landscape research projects. It finds that researchers experience participation in integrative projects as positive, in particular discussions among participants, networking, teamwork, and gaining new insights and skills. Furthermore, most researchers perceive the projects as successful and as having a positive effect on their careers. Less positive aspects of integration relate to publications and merit points. Factors found to contribute to positive experiences include reaching a high degree of integration amongst the involved disciplines, common definitions of integrative research concepts, and projects that include a large share of fundamental research as well as projects with many project outcomes. Based on these findings, we advise future projects to plan for integration, facilitate discussions, and reach agreement on integrative concepts. We suggest that aspects of fundamental research be included in integrative projects. We also suggest that planning be done at an early stage for peer-reviewed publications, to ensure that participants gain merit points from their participation in integrative research efforts.


Impact of generic substitution of anticonvulsants on the treatment of epilepsy.
Two anticonvulsants, namely phenytoin and carbamazepine, are susceptible to bioavailability problems as a result of very low water solubility and a low therapeutic ratio. In addition, phenytoin has nonlinear pharmacokinetics that exaggerate the effects of changes in the fraction of the dose absorbed. There are many published reports of bioinequivalence with different formulations of phenytoin, but fewer with carbamazepine. However, regulatory bodies have developed criteria that have to be satisfied before a new formulation is licensed, and it is therefore considered unlikely that important incidents of bioinequivalence following generic substitution will occur with these drugs in the future. As an overall source of variation in therapeutic response, bioinequivalence is negligible.However, generic substitution may cause confusion and anxiety in patients' minds when it occurs without prior warning. These effects can be allayed by information given by prescribing physicians, pharmacists and patient organisations.Given a positive approach to the issues that arise, the financial benefits of generic prescribing can be enjoyed by patients and by healthcare systems. The pharmaceutical industry should be expected to meet the challenge of fair competition in trading.


Endoscopic assisted excision of a retroclival arachnoid cyst presenting as hysterical breathlessness.
Arachnoid cysts are benign developmental cysts occurring most commonly in the middle fossa. Posterior fossa arachnoid cysts are less common, with retroclival arachnoid cysts especially in the pediatric age group being rare. We present a case of a retroclival interpeduncular farachnoid cyst in a 10-year-old boy who presented with left-sided ptosis and episodes of hysterical breathlessness. The surgical treatment involved endoscopic assisted microsurgical excision of the cyst and the child made an uneventful and complete recovery with complete cessation of breathlessness. The clinical presentation, etiopathogenesis, imaging characteristics and treatment modalities are discussed and the relevant literature reviewed.


LIBS analysis of artificial calcified tissues matrices.
In most laser-based analytical methods, the reproducibility of quantitative measurements strongly depends on maintaining uniform and stable experimental conditions. For LIBS analysis this means that for accurate estimation of elemental concentration, using the calibration curves obtained from reference samples, the plasma parameters have to be kept as constant as possible. In addition, calcified tissues such as bone are normally less "tough" in their texture than many samples, especially metals. Thus, the ablation process could change the sample morphological features rapidly, and result in poor reproducibility statistics. In the present work, three artificial reference sample sets have been fabricated. These samples represent three different calcium based matrices, CaCO3 matrix, bone ash matrix and Ca hydroxyapatite matrix. A comparative study of UV (266 nm) and IR (1064 nm) LIBS for these three sets of samples has been performed under similar experimental conditions for the two systems (laser energy, spot size, repetition rate, irradiance, etc.) to examine the wavelength effect. The analytical results demonstrated that UV-LIBS has improved reproducibility, precision, stable plasma conditions, better linear fitting, and the reduction of matrix effects. Bone ash could be used as a suitable standard reference material for calcified tissue calibration using LIBS with a 266 nm excitation wavelength.


Parents' experiences of care decisions about children with life-limiting illnesses.
To understand the 'lived experience' of parents throughout the process of making and revising end of life care decisions for their child. Three mothers who had been bereaved participated in semi-structured interviews. These were recorded, transcribed and analysed using interpretative phenomenological analysis. Two overarching themes were identified: making decisions and revising and implementing end of life care plans. Sub-themes included: who should be the decision maker; when discussions should be initiated; the values underpinning the plans; revisiting the plans; and barriers and facilitators to their implementation. Parents understand the importance of planning for the end of their child's life but find the process difficult. They also find it a challenge to verbalise their decisions at the end of their child's life and value having the decision partly taken away from them. Professionals can assist parents by using a non-dissent model of decision making. The parents' values are important in these decisions and should be elicited by professionals during the initial stages of decision making.


HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial.
The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Reported are final data up to 144 weeks of follow-up. The ISS T-002 trial was conducted in 11 clinical centers in Italy on 168 HIV positive subjects under Highly Active Antiretroviral Therapy (HAART), anti-Tat Antibody (Ab) negative at baseline, with plasma viremia <50 copies/mL in the last 6 months prior to enrollment, and CD4(+) T-cell number ≥200 cells/μL. Subjects from a parallel observational study (ISS OBS T-002, Clinicaltrials.gov NCT0102455) enrolled at the same clinical sites with the same criteria constituted an external reference group to explore biomarkers of disease. The vaccine was safe and well tolerated and induced anti-Tat Abs in most patients (79%), with the highest frequency and durability in the Tat 30 μg groups (89%) particularly when given 3 times (92%). Vaccination promoted a durable and significant restoration of T, B, natural killer (NK) cells, and CD4(+) and CD8(+) central memory subsets. Moreover, a significant reduction of blood proviral DNA was seen after week 72, particularly under PI-based regimens and with Tat 30 μg given 3 times (30 μg, 3x), reaching a predicted 70% decay after 3 years from vaccination with a half-life of 88 weeks. This decay was significantly associated with anti-Tat IgM and IgG Abs and neutralization of Tat-mediated entry of oligomeric Env in dendritic cells, which predicted HIV-1 DNA decay. Finally, the 30 μg, 3x group was the only one showing significant increases of NK cells and CD38(+)HLA-DR(+)/CD8(+) T cells, a phenotype associated with increased killing activity in elite controllers. Anti-Tat immune responses are needed to restore immune homeostasis and effective anti-viral responses capable of attacking the virus reservoir. Thus, Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy.


Cross sectional, comparative study of serum erythropoietin, transferrin receptor, ferritin levels and other hematological indices in normal pregnancies and iron deficiency anemia during pregnancy.
To test the correlation of the serum erythropoietin levels, serum transferrrin receptor levels and serum ferritin levels along with other hematological parameters in normal pregnant and anemic pregnant patients. In a prospective study, 120 pregnant women were recruited between 18 and 36 weeks of gestation; 53 normal pregnant patients, 67 anemic pregnant patients, in which, 17 had mild, 30 had moderate anemia, 20 had severe anemia. A blood sample was taken. The various hematological parameters, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), total iron binding capacity (TIBC), serum ferritin, percentage saturation of iron, serum erythropoietin (SEPO) levels, serum transferrin receptors (STfRS) were performed. For statistics, Student's 't' test, Pearson's Chi test, Mann Whitney test and Bartlett test were used as per data. MCV was significantly reduced in anemic pregnancies as compared to non-anemic pregnancies (80.2±9.6 vs 94.12±9.8fl, p=0.001), MCHC was also reduced in them (30.2±3.38% vs 34.2±2.33%, p=0.176), TIBC was significantly increased in anemic pregnancies (343.31±28.54% vs 322.88±23.84%, p=0.001), serum ferritin was significantly reduced (24.9±10.48μg/L vs 31.03±9.98μg/L, p=0.001), percentage saturation of iron was also reduced (53.85±13.21% vs 62.04±15.79%, p=0.0024), serum erythropoietin levels were significantly higher in anemic women (26.24±26.61mU/ml vs 18.12±19.08mU/ml, p=0.064). The levels were significantly higher in severe anemia (46.5±46.8mU/ml than in moderate anemia 27.4±28.1mU/ml and mild anemia 22.8±22.8mU/ml. Serum transferrin receptors were significantly higher in anemic pregnancies than in non-anemic pregnancies (1.40±0.0802μg/ml vs 1.08±0.641μg/ml, p=0.019) with rise being higher in severe anemia (2.28±0.986μg/ml) than in moderate (1.4±0.816μg/ml) and mild anemia (1.16±0.702μg/ml). Various hematological parameters especially sTfR, serum erythropoietin, serum ferritin and sTfR/log ferritin levels correlate with the severity of anemia.


Isolation and partial characterization of a broad specificity aminotransferase from Leishmania mexicana promastigotes.
A broad specificity aminotransferase (BSAT), with high activity with both, aromatic amino acids and aspartate as substrates, was purified to homogeneity from promastigotes of Leishmania mexicana by a method involving chromatography on DEAE-cellulose, Red-120-Sepharose and Mono Q, and gel filtration on Sephacryl S-200. The purified enzyme showed a single band in SDS-polyacrylamide gel electrophoresis, with an apparent molecular mass of 45 kDa. Since the apparent molecular mass of the native enzyme, determined by gel filtration, was 90 kDa, the native enzyme is a dimer of similar subunits. The amino acid composition was determined, as well as the sequence of four internal peptides obtained by tryptic digestion. Two of these peptides, consisting of 49 amino acid residues in total, showed high similarity (57%) with corresponding sequences of plant aspartate aminotransferases, whereas they had only 33% identity with the aromatic aminotransferase of Escherichia coli, and 16% identity with the tyrosine aminotransferase from the related parasite Trypanosoma cruzi. The BSAT contained only one 1/2 Cys residue per monomer. The optimal pH for the enzyme reaction, with tyrosine and alpha-oxoglutarate as substrates, was 7.0. The apparent Km values for tyrosine, phenylalanine, tryptophan and glutamate, with oxaloacetate as co-substrate, were 1.3, 0.9, 0.9 and 171.8 mM, respectively; the value for aspartate with alpha-oxoglutarate as co-substrate was 2.5 mM, and that for alanine with alpha-oxoglutarate as co-substrate was 216 mM. The values for pyruvate, alpha-oxoglutarate and oxaloacetate, with tyrosine as co-substrate, were 5.6, 0.71 and 0.12 mM, respectively. These results suggest that the enzyme is a broad-specificity aminotransferase, able to transaminate the aromatic amino acids, aspartate, and to a lower extent alanine, with high sequence similarity to aspartate aminotransferases.


Epiphyseal growth plate: evaluation with modified coronal CT.
A method of modified coronal computed tomography (CT) was developed for examination of epiphyseal growth plate arrest and neoplasms near the growth plate. Twenty-four patients were examined with this technique (26 examinations). In all cases, the growth plate and adjacent regions were well demonstrated.


Hirschsprung's disease: a comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro.
Specimens from aganglionic (constricted) and ganglionic (dilated) gut were obtained from nine patients with Hirschsprung's disease. Transmural nerve stimulation of ganglionic smooth muscle in vitro evoked an initial relaxation followed by a contraction. This contraction was reduced but not abolished by atropine and it was further reduced by substance P antagonists. Guanethidine did not affect the electrically evoked responses. In aganglionic smooth muscle, an atropine-sensitive contraction but no initial relaxation was registered. Tetrodotoxin abolished all responses to electrical stimulation in both ganglionic and aganglionic specimens. Application of carbachol or substance P produced contraction and the adrenergic agonist isoprenaline or vasoactive intestinal peptide produced relaxation in ganglionic as well as aganglionic specimens. Two other gut neuropeptides, neuropeptide Y and galanin, were without effect. The results do not indicate a different receptor set up in ganglionic v aganglionic gut. The results are compatible with a lack of noncholinergic nonadrenergic inhibitory neurons in the aganglionic gut.


Microvessel endothelial cells and pericytes increase proliferation and repress osteoblast phenotypic markers in rat calvarial bone cell cultures.
To investigate the influence of microvessel cells on osteoblasts, we exposed osteoblast-enriched cultures of rat calvarial cells to cultured endothelial cells and pericytes using feeder-layer co-cultures, co-culture dish inserts, and conditioned media experiments. When co-cultured with growth-arrested feeder-layers of endothelial cells or pericytes for 10 days, bone cell cultures showed an increase in cell number and reduction in alkaline phosphatase activity. The response of bone cells to endothelial cells was nearly twice their response to pericytes. A similar response was demonstrated by exposure to microvessel cells in co-culture dish inserts and by exposure to media conditioned by microvessel cells. In long-term cultures of bone cells, the levels of osteocalcin and the number of mineralized nodules both were reduced by exposure to media conditioned by the microvessel cells. Transient exposure to conditioned media from the microvessel cell cultures for 3 days, during the period from initial plating to cell confluence, produced nearly the same effect on the cultures of bone cells as did continuous exposure to these conditioned media. The influence of isolated microvessel cells on osteoblast-enriched calvarial cells was found to be primarily mitogenic, mediated by soluble factors, independent of cell contact, and a cause of prolonged reduction in the expression of early and late markers of the osteoblast phenotype.


A Plaque-Like CD34-Positive Dermal Fibroma Presenting as an Acquired Papule.
CD34-positive dermal fibromas (PDFs) are cutaneous neoplasms that display a characteristic pattern of superficial dermal spindle cell proliferation on histopathology evaluation. They are clinically heterogenous in presentation and thought to follow a benign course. CD34-PDFs have features that overlap with dermatofibrosarcoma protuberans (DFSP), a locally aggressive low-grade superficial sarcoma. Cytogenetic studies are essential to distinguish the two. This report presents the case of a 38-year-old female with a CD34-PDF on the right antecubital fossa.


Neonatal-onset multiple acyl-CoA dehydrogenase deficiency (MADD) in the ETFDH gene: A case report and a literature review.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting fatty acid, amino acid, and choline metabolism. The clinical manifestation of MADD is heterogeneous, from severe neonatal forms to mild late-onset forms. Here, we report a patient who presented with severe hypoglycemia and exercise intolerance suggestive of MADD. Serum tandem mass spectrometry analysis indicated elevated levels of various acyl carnitines at 25 days of age. Exome sequencing of the proband revealed compound heterozygous mutations, c. 413T>G (p.Leu138Arg) and c.1667C > G (p.Pro556Arg), in the ETFDH gene as the probable causative mutations. Based on the patient's clinical presentation and test results, the patient was diagnosed with MADD. A high-calorie and reduced-fat diet was given together with oral supplements of L-carnitine (150 mg/day). He passed away at the age of 4 months because of severe respiratory distress accompanied by muscle weakness. He passed away at the age of 4 months because of severe respiratory distress accompanied by muscle weakness. Clinicians should consider MADD in the differential diagnosis when patients present with muscle weakness and biochemical abnormalities. Gene testing plays a critical role in confirming the diagnosis of MADD and may not only prevent the need for invasive testing but also allow for timely initiation of treatment.


Risk of Intraoperative Hyperthermia and Outcomes in Adults Undergoing Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC).
Hyperthermic intraperitoneal chemotherapy (HIPEC) is commonly used to treat peritoneal surface malignancies. We aimed to identify risk factors of intraoperative patient hyperthermia and the postoperative outcome of adults undergoing HIPEC PATIENTS AND METHODS: A retrospective, IRB approved, single center cohort study was conducted. Adults treated with cytoreductive surgery and HIPEC between 2006 and 2021 were included. The primary outcome was bladder hyperthermia during perfusion, stratified by severity and duration. Secondary outcomes were postoperative complications and recurrence-free (RFS) and overall (OS) survival. Multivariable logistic regression models were fit to estimate the effects of important covariates. Out of 214 patients, 114 had mild hyperthermia (≥ 38 °C) at any time, and in 73 of these it lasted for ≥ 30 min. Independent prognostic factors of mild hyperthermia ≥ 30 min were age (OR = 0.958, 95% CI 0.933-0.984), body mas index (BMI; OR = 0.959 95% CI 0.917-1.002), gender (OR = 0.199, 95% CI 0.092-0.431), and type of chemotherapy [cisplatin versus mitomycin (OR = 0.186, 95% CI 0.070-0.491; oxaliplatin versus mitomycin (OR = 0.430, 95% CI 0.163-1.139)]. Prognostic factors of moderate-to-severe hyperthermia (≥ 39 °C) at any time were perfusion duration (OR = 1.094, 95% CI 1.018-1.177) and blood transfusion (OR = 5.689, 95% CI 1.784-18.137). Intraoperative hyperthermia was not associated with increased postoperative complications but was associated with better RFS and OS. Our study demonstrates age, gender, BMI, and chemotherapy type to be associated with hyperthermia ≥ 38 °C for ≥ 30 min, whereas longer perfusion time and blood transfusion were associated with hyperthermia ≥ 39 °C. Mild hyperthermia at the end of perfusion is associated with better RFS and OS.


Chondrogenesis in scaffolds with surface modification of elastin and poly-L-lysine.
A tissue engineering cartilage is of great importance in the current diarthrodial surgery. This study presents the formation of neocartilage by cultivating chondrocytes in elastin- and poly-L-lysine-modified scaffolds. The hybrid bulk biomaterials used contained polyethylene oxide, chitin, and chitosan and were fabricated by crosslinking, pre-freezing, and lyophilization. Bovine knee chondrocytes were seeded in the scaffolds and cultured in a spinner-flask bioreactor over 4 weeks. Surface elastin showed a better efficiency in the adhesion and proliferation of bovine knee chondrocytes in the scaffolds than surface poly-L-lysine. In addition, elastin-modified constructs yielded higher quantities of secreted glycosaminoglycans and produced collagen than poly-L-lysine-modified constructs. The surface morphology demonstrated a thriving chondrogenesis in the two kinds of constructs. The staining images revealed that elastin induced larger amounts of regenerated bovine knee chondrocytes, glycosaminoglycans, and type II collagen in the constructs than poly-L-lysine. Elastin- and poly-L-lysine-grafted polyethylene oxide/chitin/chitosan scaffolds are effective in producing cartilaginous components.


Quality of life and survival of septuagenarians and octogenarians after repair of descending and thoracoabdominal aortic aneurysms.
We assessed quality of life and survival in elderly patients after complex aortic operations to aid in surgical decision making. A retrospective review was performed of 93 patients who underwent descending thoracic aneurysm or thoracoabdominal aortic aneurysm (TAAA) repair from 2002 to 2008. A Cox model was used for survival analysis. The SF-36 Item Health Survey was administered to assess postoperative quality of life in 39 patients and was compared with age- and gender-matched normal scores. The mean age at operation was 75 ± 4.1 years; 51% of patients were male. In-hospital mortality was 15%. One-year survival was 69%, and 5-year survival was 45%. Only acute respiratory distress syndrome was a predictor of in-hospital mortality (hazard ratio = 3.75; P < .01) and 1-year mortality (hazard ratio = 4.61; P < .001). After 1 year, patients enjoyed longevity equivalent to that of a normal age- and gender-matched population (standardized mortality ratio = 1.06; P = .81). Being male is a predictor of long-term survival (hazard ratio = 0.18; P < .05). For women, extremely low and high body mass indexes (quadratic term = 0.020; P < .05) with an inflection point of body mass index of 28 is a risk factor of long-term survival. Quality of life scores were similar to those of the general population except for lower vitality scores, (s-score = -0.67, 95% CI, -1.09 to -0.26). TAAA repair in this selected older surgical population yields acceptable survival beyond the first year. Among 1-year survivors, quality of life is similar to that of an age- and gender-matched population.


In vivo investigation of tolerance and antitumor activity of cisplatin-loaded PLGA-mPEG nanoparticles.
The tolerance of BALB/c mice to different doses of blank and cisplatin-loaded PLGA-mPEG nanoparticles and the in vivo anticancer activity of these nanoparticles on SCID mice xenografted with colorectal adenocarcinoma HT 29 cells were investigated. Nanoparticles with an average size of 150-160 nm and approximately 2% w/w cisplatin content were prepared by a modified emulsification and solvent evaporation method. Normal BALB/c mice tolerated three weekly intravenous injections of a relatively high dose of blank PLGA-mPEG nanoparticles (500 mg/kg, equivalent to about 10mg nanoparticles/mouse) and three weekly intravenous injections of a high dose of nanoparticle-entrapped cisplatin (10 mg/kg). Also, histopathology examination indicated that there were no differences in the kidneys or spleens from animals treated with cisplatin-loaded nanoparticles or blank nanoparticles compared to the untreated control group. A moderate granulation of protoplasm of hepatic cells was observed in the livers from mice treated with cisplatin-loaded nanoparticles and blank nanoparticles, however, both the hepatic lobe and the portal hepatis maintained their normal architecture. The cisplatin-loaded PLGA-mPEG nanoparticles appeared to be effective at delaying tumor growth in HT 29 tumor-bearing SCID mice. The group of mice treated with cisplatin-loaded nanoparticles exhibited higher survival rate compared to the free cisplatin group. The results justify further evaluation of the in vivo antitumor efficacy of the PLGA-mPEG/cisplatin nanoparticles.


Frustrative nonreward and emotional self-medication:Factors modulating alcohol consumption following reward downshift in rats.
Life experience involving unexpected incentive loss (e.g., loss of job or a significant other) may result in negative emotional reactions (frustration) and promote alcohol drinking. Similarly, animals exposed to a frustrative 32-to-4% sucrose downshift increase their preference for alcohol (2%) vs. water. This result was interpreted as reflecting emotional self-medication-the consumption of substances that reduce negative emotions. We conducted three experiments examining parametric manipulations of the animal model: (1) effects of a severe reward downshift (32-to-4% sucrose) on consumption of various alcohol concentrations (Experiment 1); (2) effects of different magnitudes of reward downshifts on consumption of 32% alcohol (Experiment 2); and (3) effects of partial reinforcement (an intervention that increases resistance to frustration) on 2% alcohol intake induced by a 32-to-4% sucrose downshift (Experiment 3). The results show that (1) a 32-to-4% sucrose downshift leads to an increase in alcohol intake over a wide range of alcohol concentrations; (2) the greater the reward downshift, the higher the relative increase in alcohol consumption; and (3) a treatment that increases resistance to frustration (partial reinforcement) also attenuates alcohol consumption after a sucrose downshift. These data are discussed in relation to the role of frustrative nonreward in alcohol consumption.


Biliary sludge and hyperbilirubinemia associated with ceftriaxone in an adult: case report and review of the literature.
Ceftriaxone is a commonly used third-generation cephalosporin that has antimicrobial activity against many gram-positive and gram-negative organisms. Generally, ceftriaxone is a safe antibiotic; however, symptomatic biliary sludge has been reported in rare instances, most of which have involved children. It is uncommon for ceftriaxone to cause increases in laboratory indexes, such as bilirubin levels. We describe the case of a 53-year-old man who was treated with intravenous ceftriaxone 2 g every 12 hours. After 7 days of therapy, the patient's liver function test results, including total, direct, and indirect bilirubin levels, increased significantly from baseline, and the patient became jaundiced. A right upper quadrant ultrasound examination revealed biliary sludge and cholelithiasis without sonographic evidence of cholecystitis. Ceftriaxone was thought to be the responsible agent, and it was discontinued. The patient's jaundice subsided, and his liver function test results improved, returning to baseline within 14 days. Clinicians need to be aware of the association of ceftriaxone and biliary pseudolithiasis and hyperbilirubinemia, and monitor accordingly.


Effect of an acid mine drainage effluent on phytoplankton biomass and primary production at Britannia Beach, Howe Sound, British Columbia.
We investigated the effect of acid mine drainage (AMD) from an abandoned copper mine at Britannia Beach (Howe Sound, BC, Canada) on primary productivity and chlorophyll a levels in the receiving waters of Howe Sound before, during, and after freshet from the Squamish River. Elevated concentrations of copper (integrated average through the water column >0.050 mgl(-1)) in nearshore waters indicated that under some conditions a small gyre near the mouth of Britannia Creek may have retained the AMD from Britannia Creek and from a 30-m deep water outfall close to shore. Regression and correlation analyses indicated that copper negatively affected primary productivity during April (pre-freshet) and November (post-freshet). Negative effects of copper on primary productivity were not supported statistically for July (freshet), possibly because of additional effects such as turbidity from the Squamish River. Depth-integrated average and surface chlorophyll a were correlated to copper concentrations in April. During this short study we demonstrated that copper concentrations from the AMD discharge can negatively affect both primary productivity and the standing stock of primary producers in Howe Sound.


Photocatalytic properties of hierarchical BiOXs obtained via an ethanol-assisted solvothermal process.
In this study, bismuth oxyhalide (BiOXs (XCl, Br, I)) semiconductors were prepared by a simple solvothermal method, with ethanol serving as solvent and a series of tetrabutylammonium halide surfactants as halogen sources. Under identical synthetic conditions, BiOBr was more readily constructed into regular flower-like hierarchical architectures. The photocatalytic properties of the materials were studied by monitoring the degradation of rhodamine B (RhB), with visible light absorption, and colorless salicylic acid (SA). It was found that both RhB and SA were rapidly degraded on the surface of BiOBr. BiOCl was rather active for the degradation of RhB, but ineffective toward the degradation of SA. However, neither RhB nor SA could be degraded effectively in the case of BiOI. Further experiments such as UV-visible spectroscopy and detection of OH and O2(-) radicals suggest that the electronic structure of the BiOX photocatalysts is responsible for the difference in their activities.


Effects of soy protein and its hydrolysates on the formation of heterocyclic aromatic amines in roasted pork.
This study investigated the influence mechanism of soy protein and its hydrolysates (under three different degree of hydrolysis) on formation of heterocyclic aromatic amines (HAAs) formation in roasted pork. The results showed that 7S and its hydrolysates significantly inhibited the formation of quinoxaline HAAs, and the maximum inhibitory rate of MeIQx, 4,8-MeIQx, and IQx was 69%, 79%, and 100%, respectively. However, soy protein and its hydrolysates could promote the formation of pyridine HAAs (PhIP, and DMIP), its content increased significantly with the increase in the degree of hydrolysis of the protein. The content of PhIP increased 41, 54, and 165 times with the addition of SPI, 7S, and 11S at 11% degree of hydrolysis, respectively. In addition, they promoted the formation of β-carboline HAAs (Norharman and Harman), in a manner similar with that of PhIP, especially the 11S group. The inhibitory effect on quinoxaline HAAs was probably correlated with DPPH radical scavenging capacity. Nevertheless, the promotive effect on other HAAs might be related to the high levels of free amino acids and reactive carbonyls. This research may provide recommendation for the application of soy protein in high-temperature meat products.


Designing and assessing of an art-based intervention for undocumented migrants.
Undocumented immigrants and refugees are more likely to suffer from psychosocial disorders. In this pilot study, an art-based intervention is described and assessed, with a sample of 11undocumented immigrants who recently came to southern Spain on a small boat. The art-based intervention is assessed using a pre-post design and four questionnaires, which consist of The General Health Questionnaire, Beck's Depression Inventory, the Barcelona Immigrant Stress Scale and Carol Ryff's Psychological Well Being Scale. Furthermore, five participants were interviewed before and after the intervention and a thematic analysis of the transcriptions was carried out. A significant reduction of depressive symptoms with a large effect size was found. An increase of reflexive discourse and the feeling of belonging after the intervention was also observed. The study suggests that the art-based intervention decreased depressive symptoms and stress, redirecting the narratives of the participants towards the future and increasing the sense of community.


Factor V Leiden and pulmonary embolism in a young woman taking an oral contraceptive.
A 34-year-old woman with a history of asthma and oral contraceptive use died suddenly. Autopsy examination showed chronic pulmonary emboli with an acute pulmonary saddle embolus. An underlying congenital thrombophilic disorder was considered. Molecular studies on DNA isolated from blood using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis revealed coagulation factor V Leiden mutation. The incidence of venous thromboembolism in patients with factor V Leiden mutation and associated activated protein C (APC) resistance is discussed.


Monoamine Transporters as Ionotropic Receptors.
It is well established that glutamate and GABA signal through both ionotropic and metabotropic receptors. Conversely, it is thought that, with one exception, monoamines (dopamine, serotonin, and norepinephrine) signal via metabotropic receptors. Given their capacity to generate fast-acting currents, I suggest that the monoamine transporters should be considered as ionotropic receptors.


The extent of dye-coupling between exocrine acinar cells of the mouse pancreas. The dye-coupled acinar unit.
Sustained intra-acinar microiontophoretic injection of the fluorescent dye Lucifer Yellow CH in isolated fragments of mouse pancreas reveals a finite limit to the extent of intercellular communication between acinar cells. In two preparations for which complete sets of serial sections could be obtained the dye-coupled intercommunicating acinar units consisted of 110 and 230 individual exocrine acinar cells.


Self-assembly of pH-sensitive mixed micelles based on linear and star copolymers for drug delivery.
Comicellization of a star block copolymer poly(ε-caprolactone)-block-poly(diethylamino)ethyl methacrylate (S(PCL-b-PDEAEMA)) and a linear block copolymer methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-b-PCL) was developed to enhance the stability and lower the cytotoxicity of the micelles. The two copolymers self-assembled into the mixed micelles with a common PCL core surrounded by a mixed PDEAEMA/mPEG shell in aqueous solution. This core-shell structure was transformed to the core-shell-corona structure at high pH due to the collapse of the PDEAEMA segment. The properties of the polymeric micelles were greatly dependent on the weight ratio of the two copolymers and the external pH. As increasing the mPEG-b-PCL content, the size and the zeta potential of the mixed micelles were lowered while the pH-dependent stability and the biocompatibility were improved. Moreover, an increase in pH accelerated the release of indomethacin (IND) from the mixed micelles in vitro. These results augured that the mixed micelles could be applied as a stable pH-sensitive release system.


Lung injury and pneumothorax after defibrillation as demonstrated with computed tomography.
Many patients present for emergency services after electric injuries or require defibrillation during emergency services. Although the defibrillation process is safe, skin burns and myocardial injuries are reported after defibrillation procedures. There are limited data about the complications of defibrillation. In the case reported here, a lung injury and a small pneumothorax were observed after defibrillation. To the best of our knowledge, this is the first reported case in which computed tomography is used to demonstrate that a trace of electric current passed through the lung. Computed tomography may be an excellent diagnostic modality to demonstrate the severity and extent of electric injuries to the lung.


Micellar oleic and eicosapentaenoic acid but not linoleic acid influences the beta-carotene uptake and its cleavage into retinol in rats.
Improving the bioavailability of beta-carotene is vital to manage vitamin A deficiency. The influence of micellar oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) acids on plasma beta-carotene response and its conversion to retinol has been studied in rats employing single (9 h time course) and repeated (10 days) dose administrations. After a single dose, the levels (area under the curve) of plasma beta-carotene and retinyl palmitate in OA and EPA groups were higher (p < 0.05) by 13, 7 and 11, 6 folds than LA group. The liver beta-carotene level in OA and EPA groups were higher (p < 0.05) by 3 and 1.2 folds than LA group. After repeated dose, the plasma beta-carotene and retinyl palmitate levels in OA (6.2%, 51.7%) and EPA (25.4%, 17.23%) groups were higher (p < 0.05) than LA group. The liver beta-carotene level in OA (21.2%) and EPA (17.6%) groups were higher (p < 0.05) than LA group. In both the experiments, the activity of beta-carotene 15,15'-dioxygenase in the intestinal mucosa and plasma triglyceride levels were also higher in OA and EPA groups than LA group. beta-Carotene excreted through urine and feces of OA and EPA groups was lower than the LA group. These results demonstrate an improved absorption and metabolism of beta-carotene when fed mixed micelles with OA or EPA compared with LA. Although the mechanism involved in selective absorption of fatty acids needs further studies, intestinal beta-carotene uptake and its conversion to vitamin A can be modulated using specific fatty acids.


Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation.
Vasomotor symptoms (VMS), or hot flashes and night sweats, are often considered the cardinal symptoms of menopause. SWAN, one of the largest and most ethnically diverse longitudinal studies of the menopausal transition, has allowed unique insights into VMS. Specifically, SWAN has helped yield important information about the prevalence of, racial/ethnic differences in, risk factors for, and implications of VMS for midlife women's mental and physical health. We have reviewed the literature on VMS, emphasizing findings that have emerged from SWAN and new areas of inquiry in the area of VMS.


Cationised dextran and pullulan modified with diethyl aminoethyl methacrylate for gene delivery in cancer cells.
This work describes the synthesis and characterisation of cationised dextran and pullulan modified with diethyl aminoethyl methacrylate (DEAEM) for gene delivery in cancer cells. To dextran and pullulan, PEI was conjugated to impart cationicity. These cationised polysaccharides were then modified with DEAEM monomer via Michael addition reaction and synthesised four different derivatives viz DPD I, DPD II, PPD I and PPD II. These vectors form nanocomplexes with DNA exhibiting positive zeta potential. These nanoplexes are cytocompatible in C6, HeLa and L929 cells. Transfection efficiency of these vectors was evaluated using p53 plasmid which demonstrated good transfection in cancer cells (C6 and HeLa) alone. Biodistribution studies of DPD II and PPD II in BALB/c mice shows its tendency to accumulate in liver tissue and not in any vital organs like brain, lungs and heart. In addition, these derivatives also exhibit good renal clearance.


The nature of surgical error: a cautionary tale and a call to reason.
Errors and "patient safety" have taken on monumental importance for surgery. Like all things new, there is an initial over-reaction before a return to a balanced perspective. The current response to the global interest in error has been to seize on the latest reports that are focusing on the "systemic nature" of errors, which is also being referred to as "the new look." There has been an unintentional ignoring of the actual error, referred to as the coface error, that the surgeon commits. It is time to put the approach to errors into perspective and redefine errors within the context of the surgical community, which can result in a balance of the surgeon's position in regard to systemic and personal responsibility.


Iron-ozone catalytic oxidation reactive filtration of municipal wastewater at field pilot and full-scale with high-efficiency pollutant removal and potential negative CO2 e with biochar.
Iron-ozone catalytic oxidation (CatOx) shows promise in addressing challenging wastewater pollutants. This study investigates a CatOx reactive filtration (Fe-CatOx-RF) approach with two 0.4 L/s field pilot studies and an 18-month, 18 L/s full-scale municipal wastewater deployment. We apply ozone to leverage common sand filtration and iron metal salts used in water treatment into a next-generation technology. The process combines micropollutant and pathogen destructive removal with high-efficiency phosphorus removal and recycling as a soil amendment, clean water recovery, and the potential for carbon-negative operation with integrated biochar water treatment. A key process innovation is converting a continuously renewed iron oxide coated, moving bed sand filter into a "sacrificial iron" d-orbital catalyst bed after adding O3 to the process stream. Results for the Fe-CatOx-RF pilot studies show >95% removal efficiencies for almost all >5 × LoQ detected micropollutants, with removal rates slightly increasing with biochar addition. Phosphorus removal for the pilot site with the most P-impacted discharge was >98% with serial reactive filters. The long-term, full-scale Fe-CatOx-RF optimization trials showed single reactive filter 90% TP removal and high-efficiency micropollutant removals for most of the compounds detected, but slightly less than the pilot site studies. TP removal decreased to a mean of 86% during the 18 L/s, 12-month continuous operation stability trial, and micropollutant removals remained similar to the optimization trial for many detected compounds but less efficient overall. A >4.4 log reduction of fecal coliforms and E. coli in a field pilot sub-study suggests the ability of this CatOx approach to address infectious disease concerns. Life cycle assessment modeling suggests that integrating biochar water treatment into the Fe-CatOx-RF process for P recovery as a soil amendment makes the overall process carbon-negative at -1.21 kg CO2 e/m3 . Results indicate positive Fe-CatOx-RF process performance and technology readiness in full-scale extended testing. Further work exploring operational variables is essential to establish site-specific water quality limitations and responsive engineering approaches for process optimization. PRACTITIONERS POINTS: Adding ozone to WRRF secondary influent flows into tertiary ferric/ferrous salt dosed sand filtration amplifies a mature reactive filtration technology into a catalytic oxidation process for micropollutant removal and disinfection. Expensive catalysts are not used. Iron oxide compounds used to remove phosphorus and other pollutants act as sacrificial catalysts with ozone, and these rejected iron compounds can be returned upstream to aid in secondary process TP removal. Biochar addition to the CatOx process improves CO2 e sustainability and phosphorus removal/recovery for long-term soil and water health. Short duration field pilot scale and 18-month full-scale operation at three WRRFs with good results demonstrate technology readiness.


Topotecan plus carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a meta-analysis of randomized controlled trials.
To evaluate whether the addition of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. Meta-analysis was performed using a random effects model. Four randomized controlled trials with a total of 3632 patients were identified and included in the meta-analysis. No significant differences were observed in terms of progression-free survival (P=0.400), overall survival (P=0.502) and overall response rate (P=0.953) between patients treated with topotecan plus carboplatin and paclitaxel versus carboplatin and paclitaxel. However, there were significantly higher rates of grade 3-4 leucopenia (P=0.024), neutropenia (P<0.001), anaemia (P<0.001), and thrombopenia (P<0.001) in the topotecan plus carboplatin and paclitaxel group. No significant differences were observed in grade 3-4 nausea (P=0.352) and vomiting (P=0.092) between these two groups. Topotecan plus carboplatin and paclitaxel did not improve survival outcomes and caused more haematological toxicity for advanced ovarian cancer.


Comparing Patient Selection and 30-day Outcomes Between Single Anastomosis Gastric Bypass and Roux-en-Y Gastric Bypass: a Retrospective Cohort Study of 47,384 Patients.
Single anastomosis gastric bypass (SAGB) offers a novel bariatric procedure with increasing popularity. However, its adoption, patient selection, and short-term safety remain poorly characterized. The 2020 Metabolic and Bariatric Accreditation and Quality Improvement Program (MBSAQIP) was analyzed comparing SAGB to Roux-en-Y gastric bypass (RYGB). Bivariate analysis and multivariable logistic regression models compared difference between groups and factors associated with 30-day serious complications and mortality. Overall, 47,384 patients were evaluated, with 1344 (2.8%) undergoing SAGB. SAGB patients had a higher BMI (45.2 ± 7.6 kg/m2 vs 44.6 ± 7.9 kg/m2, p = 0.006) and younger age (44.3 ± 12.1 years vs. 45.4 ± 11.5 years, p = 0.0008) than RYGB patients respectively. SAGB patients were less likely to have GERD (42.6% SAGB vs. 45.7% RYGB, p = 0.02), sleep apnea (37.8% SAGB vs. 41.1% RYGB, p = 0.02), and chronic steroid use (1.3% SAGB vs. 2.2% RYGB, p = 0.04). There were no significant difference in diabetes, hypertension, or dyslipidemia rates. Operative length for SAGB was significantly less than for RYGB (101 ± 53.7 min SAGB vs. 131.5 ± 63.3 min RYGB, p < 0.0001). SAGB was independently associated with decreased serious complications (4.7% vs. 8.4%, p < 0.0001) within 30 days compared to RYGB. Additionally, SAGB patients were less likely to experience reoperation (1.6% vs. 2.6%, p = 0.03), and readmission (2.2 vs. 5.8%, p < 0.0001) compared to RYGB respectively. Compared to RYGB, patients undergoing SAGB were younger with marginally higher BMI. After adjusting for comorbidities, SAGB was associated with decreased odds of serious complications. Ongoing prospective studies analyzing long-term outcomes following SAGB remain needed.


Relationship between a near Melanocortin-4 receptor gene variant and puberty timing in children is vague unlike obesity.
Obesity is a complicated phenomenon which is a combination of genetic, environmental, and psychological factors. Genetic factors of obesity play an important role in individual risk. It is well known that obese children have disturbed puberty timing. To the best of our knowledge, no study has been performed to investigate the association between MC4R gene mutation and puberty timing. This study was performed as a cross-sectional study evaluating the near MC4R rs17782313 variation in 60 obese children and 98 healthy non obese children. Weight, height, BMI ( Body Mass Index ), BMI z-score (BMIz), family history of diabetes mellitus and obesity, the age of the obesity onset, overeating behavior, type of obesity (central or general) and puberty stage were evaluated in 60 obese children. The average age of the participants was 14.87 (+/- 1.3) years, with average weight and BMI of 90.77 (+/-12.2) Kg and 31.72 (+/-4.35) Kg/m2, respectively. Compared to healthy non obese patients, those with C-T genotype (C-T Vs. T-T and C-C) had higher odds of obesity than those with T-T and C-C genotype (p < 0.0001) while genotype TT showed significant protective effect (p = 0.0007). The heterozygote individuals (CT) have a higher BMIz than homozygote ones (CC and TT) (2.8 vs. 2.5 Kg/m2, p = 0.04). children with CT genotype have 5.1 increased risk of obesity. While genotype TT showed significant obesity protective effect. We did not find association of this polymorphism with either childhood eating disorders or puberty. It is recommended to perform a cohort study in a larger sample. The online version contains supplementary material available at 10.1007/s40200-022-01011-5.


Renography in the foetal and newborn lamb.
Hippuran renography indicates kidney function as reflected in a substance handled mainly by the tubules. The working conditions of the kidneys undergo a fundamental change at birth with the cessation of placenta circulation, and these organs become responsible for waste elimination. 131I-hippuran renography was performed on foetal and newborn lambs using a gamma camera and a computer. The intervals of the maximum- and half-time renal activity were determined. These decreased by a half from mean foetal value of Tm=7 mi and T12=19 min in 1 to 1.5 days and reached the full-grown level in 2 to 5 weeks. No sudden change occurred as a result of the first breath.


Using propensity scores to estimate the effectiveness of maternal and newborn interventions to reduce neonatal mortality in Nigeria.
Nigeria is the largest country in sub-Saharan Africa, with one of the highest neonatal mortality rates and the second highest number of neonatal deaths in the world. There is broad international consensus on which interventions can most effectively reduce neonatal mortality, however, there is little direct evidence on what interventions are effective in the Nigerian setting. We used the 2013 Nigeria Demographic and Health Survey (NDHS) and the follow-up 2014 Verbal and Social Autopsy study of neonatal deaths to estimate the association between neonatal survival and mothers' and neonates' receipt of 18 resources and interventions along the continuum of care with information available in the NDHS. We formed propensity scores to predict the probability of receiving the intervention or resource and then weighted the observations by the inverse of the propensity score to estimate the association with mortality. We examined all-cause mortality as well as mortality due to infectious causes and intrapartum related events. Among 19,685 livebirths and 538 neonatal deaths, we achieved adequate balance for population characteristics and maternal and neonatal health care received for 10 of 18 resources and interventions, although inference for most antenatal interventions was not possible. Of ten resources and interventions that met our criteria for balance of potential confounders, only early breastfeeding was related to decreased all-cause neonatal mortality (relative risk 0.42, 95% CI 0.32-0.52, p < 0.001). Maternal decision making and postnatal health care reduced mortality due to infectious causes, with relative risks of 0.29 (95% CI 0.09-0.88; 0.030) and 0.46 (0.22-0.95; 0.037), respectively. Early breastfeeding and delayed bathing were related to decreased mortality due to intrapartum events, although these are not likely to be causal associations. Access to immediate postnatal care and women's autonomous decision-making have been among the most effective interventions for reducing neonatal mortality in Nigeria. As neonatal mortality increases relative to overall child mortality, accessible interventions are necessary to make further progress for neonatal survival in Nigeria and other low resource settings.


Multi-Elements in Source Water (Drinking and Surface Water) within Five Cities from the Semi-Arid and Arid Region, NW China: Occurrence, Spatial Distribution and Risk Assessment.
The purpose of this study was to identify the concentration of multi-elements (MEs) in source water (surface and drinking water) and assess their quality for sustainability. A total of 161 water samples including 88 tap drinking waters (DW) and 73 surface waters (SW) were collected from five cities in Xi'an, Yan'an, Xining, Lanzhou, and Urumqi in northwestern China. Eighteen parameters including pH, electrical conductivity (EC), total organic carbon (TOC) total nitrogen (TN), chemical compositions of anions (F-, Cl-, NO₃-,HCO₃-, SO₄2-), cations (NH₄⁺, K⁺, Na⁺, Ca2+,Mg2+), and metals (lead (Pb), chromium (Cr), cadmium (Cd), copper (Cu)) were analyzed in the first time at the five cities . The results showed that pH values and concentrations of Cl-, SO₄2-, Na⁺, K⁺, Ca2+, Mg2+ and Cd, Cr, Cu in DW were within the permissible limits of the Chinese Drinking Water Quality Criteria, whereas the concentrations of other ions (F-, NO₃-, NH₄⁺ and Pb) exceeded their permissible values. In terms of the SW, the concentrations of F-, Cl-, NO₃-, SO₄2- were over the third range threshold i.e., water suitable for fishing and swimming of the Surface Water Quality Standards in China. The spatial distributions of most MEs in source water are similar, and there was no clear variation for all ions and metals. The metals in DW may be caused by water pipes, faucets and their fittings. The noncarcinogenic risk of metals in DW for local children are in decreasing order Cr > Cd > Pb > Cu. The carcinogenic risk from Cr exposure was at the acceptable level according to threshold of USEPA. Although the comprehensive index of potential ecological assessment of Cr, Cd, Pb and Cu in SW ranked at low risk level and was in the order of Huang River in Xining > Peaceful Canal in Urumqi > Yan River in Yan'an > Yellow River in Lanzhou, their adverse effects to ecology and human health at a low concentration in local semi-arid and arid areas should not be ignored in the long run.