Are the physicochemical properties of antibacterial compounds really different from other drugs?
It is now widely recognized that there is an urgent need for new antibacterial drugs, with novel mechanisms of action, to combat the rise of multi-drug resistant bacteria. However, few new compounds are reaching the market. Antibacterial drug discovery projects often succeed in identifying potent molecules in biochemical assays but have been beset by difficulties in obtaining antibacterial activity. A commonly held view, based on analysis of marketed antibacterial compounds, is that antibacterial drugs possess very different physicochemical properties to other drugs, and that this profile is required for antibacterial activity. We have re-examined this issue by performing a cheminformatics analysis of the literature data available in the ChEMBL database. The physicochemical properties of compounds with a recorded activity in an antibacterial assay were calculated and compared to two other datasets extracted from ChEMBL, marketed antibacterials and drugs marketed for other therapeutic indications. The chemical class of the compounds and Gram-negative/Gram-positive profile were also investigated. This analysis shows that compounds with antibacterial activity have physicochemical property profiles very similar to other drug classes. The observation that many current antibacterial drugs lie in regions of physicochemical property space far from conventional small molecule therapeutics is correct. However, the inference that a compound must lie in one of these "outlier" regions in order to possess antibacterial activity is not supported by our analysis. Graphical abstract.


Zucchini tigré mosaic virus is a distinct potyvirus in the papaya ringspot virus cluster: molecular and biological insights.
In recent years, three new potyviruses have been described in the papaya ringspot virus (PRSV) cluster. In addition, two types of PRSV are recognized, type W, infecting cucurbit plants, and type P, infecting papaya and also cucurbits. A third type, PRSV-T, was also partially described in Guadeloupe. Complete genome sequencing of four PRSV-T isolates showed that this virus is a related virus that is distinct from PRSV, and the name zucchini tigré mosaic virus (ZTMV) is proposed, in reference to the typical symptoms observed in zucchini squash. Eleven other viral isolates from different geographic origins were confirmed as ZTMV isolates using the complete sequence of the cylindrical inclusion (CI) coding region, whereas pairwise sequence similarities in the coat protein (CP) coding region did not unambiguously distinguish ZTMV isolates from PRSV isolates. The use of the CI coding region for species demarcation appears more suitable than the CP coding region for closely related viruses. Principal coordinates analysis based on the biological behavior of the viral isolates studied clustered PRSV-P, PRSV-W and ZTMV isolates into three different groups. Therefore, ZTMV is different from PRSV in its molecular and biological properties.


Angiotensin converting enzyme (ACE).
Angiotensin converting enzyme (ACE) was isolated as a 'hypertensinconverting enzyme'. There have been considerable advances in understanding the metabolic role of ACE in the body. This review attempts to highlight the role of ACE enzyme in the physiological and pathological processes occurring in the organs in which it is localized. The literature was searched from the websites of the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) and Pub Med Central, the U.S. National Library of Medicine's digital archive of life sciences journal literature. The involvement of ACE in regulation of blood pressure forms its central action but it has a role to play in a variety of physiological processes occurring in the organs in which it is localized like the lungs, macrophages, brain, pancreas, liver etc. It has also been implicated in the pathogenesis of a number of diseases including COVID-19. More studies need to be carried out in order to validate the use of ACE levels in the diagnosis and monitoring of the diseases associated, and facilitate the use of ACE inhibitors and Angiotensin Receptor Blockers in the management of the same, so this wonder molecule can be utilized to its full potential.


cGAS-STING, an important pathway in cancer immunotherapy.
Cytosolic DNA sensing, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is an important novel role in the immune system. Multiple STING agonists were developed for cancer therapy study with great results achieved in pre-clinical work. Recent progress in the mechanical understanding of STING pathway in IFN production and T cell priming, indicates its promising role for cancer immunotherapy. STING agonists co-administrated with other cancer immunotherapies, including cancer vaccines, immune checkpoint inhibitors such as anti-programmed death 1 and cytotoxic T lymphocyte-associated antigen 4 antibodies, and adoptive T cell transfer therapies, would hold a promise of treating medium and advanced cancers. Despite the applications of STING agonists in cancer immunotherapy, lots of obstacles remain for further study. In this review, we mainly examine the biological characters, current applications, challenges, and future directions of cGAS-STING in cancer immunotherapy.


Effects of intraventricular injections of norepinephrine on brain-pituitary-ovarian function in the rabbit.
In estrous estrogen-primed female rabbits with electrodes chronically implanted in various subcortical regions of the brain, the intraventricular injection of an ovulation-inducing dose of norepinephrine (NE) stimulated a prolonged episode of high amplitude 40-60 cps electroencephalographic (EEG) activity in the olfactory bulb (OB) and its projections. This activity, which started usually between 30 and 60 min after NE injection and was maintained continously for periods up to an hour thereafter, was regularly absent in the same rabbits when they were pseudopregnant and non-ovulatory to NE. Similar OB-EEG activity and ovulation had been observed earlier in response to intraventricular histamine under light pentobarbital anesthesia. The ovulatory response to histamine was eliminated by massive midbrain lesions or removal of the olfactory bulb, but intraventricular NE still induced ovulation after such losses. The ovulatory effectiveness of NE was blocked, however, by low doses of pentobarbital or high doses of atropine, neither of which inhibited the ovulatory response to intraventricular epinephrine. Atropine and alpha-adrenergic blocking agents also prevented the ovulatory response to intraventricular histamine. It is suggested that histamine activates pituitary-ovarian function by stimulating central noradrenergic elements and that NE has more of the physiological-pharmacological characteristics of a natural central nervous activator of luteinizing hormone-releasing hormone than has epinephrine.


Burden of depression and anxiety among patients with inflammatory bowel disease: results of a nationwide analysis.
The burden of psychiatric disorders is on a rise in inflammatory bowel disease (IBD) patients which has shown to effect medication compliance and overall clinical outcomes. We studied the prevalence of depression and anxiety in IBD patients when compared to individuals with other chronic medical conditions. This is a retrospective cohort study using the United States national inpatient sample of 2016 to 2018. We identified patient encounters with a diagnosis of IBD. Our primary outcome was prevalence of depression and anxiety in IBD patients when compared to general adult population with other chronic medical conditions. We further studied these outcomes in subgroups of patients with ulcerative colitis and Crohn's disease. A total of 963,619 patient encounters were identified with the diagnosis of IBD between 2016 and 2018, of them 162,850 (16.9%) had depression and 201,685 (20.9%) had anxiety. The prevalence of depression and anxiety was significantly higher in IBD patients in comparison to general population, (16.9% vs 12.3%) and (20.9% vs 15%) respectively (p < 0.001). Association of depression and anxiety was also higher in IBD patients when compared to patients with other chronic conditions like diabetes, metastatic cancer, and coronary artery disease. Crohn's disease and ulcerative colitis were independently associated with increased odds of depression and anxiety and these results were statistically significant (p < 0.001). IBD is associated with increased prevalence of depression and anxiety when compared to general population. Association of these psychiatric illnesses with IBD is significantly higher when compared to other chronic medical conditions.


Long-term complications of diabetes mellitus, Part II: Gastrointestinal and infectious.
Numerous gastrointestinal and infectious diseases are associated with long-standing and often poorly controlled DM in humans. Although not as well documented in veterinary patients, the veterinary practitioner must always have an index of suspicion for the possibility of these complications. Because the clinical signs of a number of these problems are identical, proper diagnostic procedures need to be used to differentiate among the gastrointestinal and even infectious problems. In all cases, stringent blood glucose control is the common denominator in effective treatment. Other agents can be used both to assist in short-term control and for long-term therapy.


Cis-dichlorodiammine platinum (II) in advanced ovarian carcinoma.
Twenty-seven patients with advanced ovarian cancer were treated with a total of 80 courses of cis-dichlorodiammine platinum (II) (cisplatin). The doses in three courses were less than 50 mg/m2, in 64 courses they were 50 mg/m2, and in eight courses they were 100 mg/m2. In addition, five courses of low-dose daily treatment (20 mg/m2 for five days) were administered. Twelve patients received cisplatin alone, 12 received cisplatin and cyclophosphamide (750 mg/m2), and three patients received cisplatin with other drugs. There were eight responders (33%) in the 24 evaluable patients. Renal toxicity occurred in four patients, ototoxicity in four, and leucopenia (which was life-threatening in one patient) occurred in 16 patients (white cell count less than 3.0 X 10(9)/L). There were two early drug-related deaths. The median survival of patients who responded to cisplatin treatment was longer than 30 weeks compared with nine weeks for non-responders.


Densitometry as an aid in amniotic fluid gel acetylcholinesterase analysis.
We have performed gel acetylcholinesterase analysis blindly on 1,300 consecutive amniotic fluid samples sent to our laboratory for alpha-fetoprotein measurement. Faint acetylcholinesterase bands were identified in nine of 1,300 samples, and all of these were associated with pregnancies free of major fetal malformations. Dense acetylcholinesterase bands were identified in four samples, and all were associated with major fetal malformations. Densitometric analysis of acetylcholinesterase bands provided additional objectivity in classifying band density.


Follow-up study of patients with bridge constructions performed by private dental surgeons and at a university clinic, 8 years following insertion.
Patients treated in private practice and patients treated at the Department of Prosthetic Dentistry of the Faculty of Odontology in Gothenburg with fixed bridgework were questioned about their experience of their bridges. The interview was carried out with questionnaires and in some cases by telephone. The results were similar in both groups, and the patients were satisfied with the treatment.


Incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases.
Adverse events associated with re-irradiation for painful bone metastases have not been adequately evaluated. The purpose of this study was to clarify the incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases. Data for 61 consecutive patients who required re-irradiation for spine or pelvic bone metastases between April 2009 and March 2013 were retrospectively evaluated in this study. The adverse events, biologically effective dose (BED), and the responses to pain and/or symptoms caused by cord compression were evaluated. Of the 61 patients, 52 were included in the study and their data were analyzed. The site of re-irradiation was the spine in 35 patients (67 %), and the pelvic bone in the remaining 17 patients (33 %). The median follow-up period was 170 days (range 5-1,644 days) for all eligible patients. The median interval from initial radiation therapy to re-irradiation was 161 days (range 26-2,909 days). The median cumulative BED from the initial radiation and re-irradiation was 115 Gy (range 80-155 Gy2). The acute adverse events were all below grade 2 in severity, except for two patients who showed grade 3 pain flare within a few days after the start of re-irradiation. No late adverse events were observed in this study that were grade 3 or of worse severity. The incidence and severity of adverse events after re-irradiation for spine or pelvic bone metastases were within acceptable limits in this study.


Effects of hunger on neuronal histone modifications slow aging in Drosophila.
Hunger is an ancient drive, yet the molecular nature of pressures of this sort and how they modulate physiology are unknown. We find that hunger modulates aging in Drosophila. Limitation of branched-chain amino acids (BCAAs) or activation of hunger-promoting neurons induced a hunger state that extended life span despite increased feeding. Alteration of the neuronal histone acetylome was associated with BCAA limitation, and preventing these alterations abrogated the effect of BCAA limitation to increase feeding and extend life span. Hunger acutely increased feeding through usage of the histone variant H3.3, whereas prolonged hunger seemed to decrease a hunger set point, resulting in beneficial consequences for aging. Demonstration of the sufficiency of hunger to extend life span reveals that motivational states alone can be deterministic drivers of aging.


Cloning and characterization of a surface antigen of Eimeria tenella merozoites and expression using a recombinant vaccinia virus.
A rabbit serum raised against Eimeria tenella merozoites was used to screen a lambda gt11 cDNA library made from merozoite mRNA of E. tenella. The insert of the phage clone lambda Mz 5-7 revealed an open reading frame consisting of 945 nucleotides, encoding a 33-kDa protein. This size is consistent with the size of a protein translated in vitro from merozoite mRNA and immunoprecipitated with monospecific anti-Mzp 5-7 antibodies. A smaller protein of 24 kDa, located on the surface of the parasite, also reacted with the monospecific antiserum and is the potential processed form of the Mzp 5-7. Furthermore, a recombinant vaccinia virus expressing the Mzp 5-7 antigen was constructed and used to immunize chickens.


Presence of endoarterial dispositives regulating retinal blood circulation.
We have observed for the first time some pedunculated blocking formations of the central retinal artery. Their function could be to regulate retinal blood perfusion.


Determination of radioactive elements and heavy metals in sediments and soil from domestic water sources in northern peninsular Malaysia.
Soil serves as a major reservoir for contaminants as it posseses an ability to bind various chemicals together. To safeguard the members of the public from an unwanted exposure, studies were conducted on the sediments and soil from water bodies that form the major sources of domestic water supply in northern peninsular Malaysia for their trace element concentration levels. Neutron Activation Analysis, using Nigeria Research Reactor-1 (NIRR-1) located at the Centre for Energy Research and Training, Zaria, Nigeria was employed as the analytical tool. The elements identified in major quantities include Na, K, and Fe while As, Br, Cr, U, Th, Eu, Cs, Co, La, Sm, Yb, Sc, Zn, Rb, Ba, Lu, Hf, Ta, and Sb were also identified in trace quantities. Gamma spectroscopy was also employed to analyze some soil samples from the same area. The results indicated safe levels in terms of the radium equivalent activity, external hazard index as well as the mean external exposure dose rates from the soil. The overall screening of the domestic water sources with relatively high heavy metals concentration values in sediments and high activity concentration values in soil is strongly recommended as their accumulation overtime as a consequence of leaching into the water may be of health concern to the members of the public.


Chronic intramedullary infusion of prostaglandin E2 stimulates bone formation both in the bone marrow and in the periosteum.
Prostaglandin E2 (PGE2) has a potent bone resorbing activity in vitro, but some recent studies have shown that PGE2 stimulates bone formation in vivo. The effects of PGE2 on the bone are therefore still controversial. We attempted to reveal the effects of PGE2 on bone in vivo more directly; we injected PGE2 continuously into the bone marrow and onto the periosteum and examined the local effects of PGE2 histologically or by bone densitometry. Following PGE2 infusion into the bone marrow, new bone was formed in the bone marrow around the infused site and following PGE2 infusion onto the periosteum, extensive periosteal bone formation was observed. Bone mineral content was also increased significantly in the PGE2 infused bones. The administration of cyclic AMP did not mimic the effects of PGE2. In contrast to in vitro experiments, the in vivo effect of PGE2 is predominantly to produce bone.


SaliVISION: a rapid saliva-based COVID-19 screening and diagnostic test with high sensitivity and specificity.
The Coronavirus disease 2019 (COVID-19) pandemic-caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- has posed a global threat and presented with it a multitude of economic and public-health challenges. Establishing a reliable means of readily available, rapid diagnostic testing is of paramount importance in halting the spread of COVID-19, as governments continue to ease lockdown restrictions. The current standard for laboratory testing utilizes reverse transcription quantitative polymerase chain reaction (RT-qPCR); however, this method presents clear limitations in requiring a longer run-time as well as reduced on-site testing capability. Therefore, we investigated the feasibility of a reverse transcription looped-mediated isothermal amplification (RT-LAMP)-based model of rapid COVID-19 diagnostic testing which allows for less invasive sample collection, named SaliVISION. This novel, two-step, RT-LAMP assay utilizes a customized multiplex primer set specifically targeting SARS-CoV-2 and a visual report system that is ready to interpret within 40 min from the start of sample processing and does not require a BSL-2 level testing environment or special laboratory equipment. When compared to the SalivaDirect and Thermo Fisher Scientific TaqPath RT-qPCR testing platforms, the respective sensitivities of the SaliVISION assay are 94.29% and 98.28% while assay specificity was 100% when compared to either testing platform. Our data illustrate a robust, rapid diagnostic assay in our novel RT-LAMP test design, with potential for greater testing throughput than is currently available through laboratory testing and increased on-site testing capability.


Binucleate cells in the Ehrlich ascites tumor. Autoradiographic labeling.
An autoradiographic study was performed on binucleate and mitotic cells in the Ehrlich ascites tumor (EAT) untreated and after treatment with 5-fluorouracil (FU). The number of binucleate cells was greater in the treated tumor than in the controls. It was also observed that the number of labeled mitoses was greater in the Fu-treated tumor. Autoradiographic labeling showed that the cells that proved to be binucleate had previously passed through S-phase; thus, these cells belonged to the proliferative compartment.


[An emergent surgical treatment of recurrent Stanford type A thrombosed aortic dissection].
A 71-year-old male was admitted to our hospital with a chief complaint of back pain. Chest CT scan showed so-called Stanford type A thrombosed aortic dissection. Aortography revealed no ulcer like projection. At first, conservative treatment was carried out. But about two hours later, he had another back pain. Repeat chest CT scan demonstrated an enlarged dissecting lumen, necessitating emergent graft replacement. Postoperative course was uneventful and he was discharged on the 33rd postoperative days.


Neuronal ceroid lipofuscinoses.
Neuronal ceroid lipofuscinoses (NCL) represent a group of autosomal recessive neurodegenerative disorders, presenting with myoclonic epilepsy, psychomotor delay, progressive loss of vision, and early death. Four main clinical forms have been delineated (infantile, late infantile, juvenile, and adult), but many other variants have also been described. At least 14 genetically distinct NCL, designated CLN1 to CLN14, are presently known.The identification of the deficient protein and/or the genetic defect is required for a specific diagnosis, which is necessary for a reliable genetic counseling in at-risk families.


Histological Evaluation of Gonad Impairments in Russian Sturgeon (Acipenser gueldenstaedtii) Reared in Recirculating Aquatic System (RAS).
The aim of the study was to raise an issue concerning gonadal impairments in sturgeon reared in recirculating aquatic systems (RAS). In the present study, an in-depth histological evaluation in terms of gonadal pathologies was performed on over-4-year-old (1600 days post-hatching) Russian sturgeon (Acipenser gueldenstaedtii) reared under indoor RAS. A female-biased sex ratio, intersex occurrence, ovarian fat overgrowth, T-cell infiltration and follicle atresia were the most commonly observed disorders in the analyzed gonads. The combined processes of oocyte autophagy and follicular cell apoptosis were engaged in follicular atresia; however, atretic follicles showed a varied morphology, whereas oogonia and oocytes in the early stages of meiosis, as well as spermatogonia, underwent degeneration by apoptosis. The most severe pathology was observed in females with abundant intra-ovarian fat deposition. The extremely fatty ovaries were noted to lose the majority of ovarian follicles, which directly leads to fish sterility. The identified impairments might be related to estrogenic endocrine disruption, as feminization and unspecific vitellogenin synthesis were detected, although the sources of the observed pathologies can be diverse. Therefore, the presented research lays the groundwork for further studies on reproductive disorders in this prized and endangered fish species.


[Severe hyperthermia syndrome in the infant. Apropos of 11 cases].
The authors report a retrospective study of 11 cases of malignant hyperthermia. The mean age of the patients was 5 months and 3 weeks. Clinical features included severe hyperthermia (greater than 41 degrees C), seizures, coma, collapse, rhabdomyolysis, acute renal failure and functional renal failure. Three infants died. Four patients presented neurological damages. Four recovered fully. The authors discuss the difficulties of diagnosis, the nosological position and the pathophysiology of this syndrome.


Stem Cell as Vehicles of Antibody in Treatment of Lymphoma: a Novel and Potential Targeted Therapy.
Lymphoma is a heterogeneous malignancy and its incidence is increasing in the past decades all over the world. Although more than half of lymphoma patients achieve complete or partial remission from the standard first-line ABVD or R-CHOP based therapy, patients who fail to respond to these regimens will give rise to relapsed or refractory (R/R) lymphoma and may lead to a worse prognosis. Developing novel agents is important for R/R lymphoma. Based on the homing ability and being genetically modified easily, stem cells are usually used as vehicles in cell-based anti-tumor therapy, which can not only retain their own biological characteristics, but also make anti-tumor agents secrete constantly in tumor environment, to eventually kill the tumor cells more effectively. In this review, we will briefly introduce the properties of antibody therapy carried by stem cells, especially the hopes and hurdles of stem cell-mediated antibody secretion in the treatment of lymphoma.


Marketing consultation-liaison psychiatry.
Consultation-liaison (C-L) psychiatry has demonstrated its potential to serve as a significant interface between psychiatry and the rest of medicine in health care service delivery, academic teaching, and collaborative research. The extent to which that potential is not broadly acknowledged reflects the specialty's failure to communicate effectively the contributions C-L psychiatry has to offer to the general medical community. Marketing principles, which emphasize the importance of defining a product in terms attractive to carefully targeted consumers, evaluating and refining the product to ensure its continued acceptance and use by the market, and communicating the availability of the product, offer a means of fostering the visibility and utilization of C-L psychiatry toward the end of improved quality of care.


[Calculator processing measurement results for occupational vibration and acoustic factors].
The article deals with calculator designed to simplify and speed up processing of measurement results for occupational noises and vibration, calculation examples are presented.


Geriatric impairments were directly and indirectly associated with mortality in older patients with cancer: a structural equation analysis.
We assessed the direct and indirect effects between six geriatric domains and 6- and 12-month mortality in older cancer patients. We included cancer patients aged ≥70 years from the Elderly Cancer Patients cohort, referred for geriatric assessment between 2007 and 2016. We used structural equation modelling to examine the interrelationships between six geriatric domains (function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support) and the direct and indirect relationships between these domains, the cancer stage, site, and treatment on the one hand and mortality on the other. The analysis included 1,434 patients (mean age: 80 ± 5.6 years; women: 48%; main cancer sites: digestive tract [36.2%], urinary tract and prostate [26.6%], and breast [16.5%]; metastatic cancer: 48%). Direct relationships to 6- and 12-month mortality were identified for functional impairment (standardized coefficient [SC]: 0.37 [P < 0.001] and 0.32 [P < 0.001], respectively), poor nutritional status (SC: 0.11 [P = 0.005] and 0.14 [P = 0.001]), poor social support (SC = 0.07 [P = 0.08] and 0.09 [P = 0.02]), cancer site, stage, and treatment. The effects of comorbidities, cognitive impairment, and depression on mortality were mediated by functional and nutritional status. In older cancer patients, functional and nutritional impairments were the strongest direct prognostic geriatric factors for mortality.


Total management of chronic obstructive pulmonary disease (COPD) as an independent risk factor for cardiovascular disease.
Patients with cardiovascular disease (CVD) often have multiple comorbid conditions that may interact with each other, confound the choice of treatments, and reduce mortality. Chronic obstructive pulmonary disease (COPD) is one of the most important comorbidities of CVD, which causes serious consequences in patients with ischemic heart disease, stroke, arrhythmia, and heart failure. COPD shares common risk factors such as tobacco smoking and aging with CVD, is associated with less physical activity, and produces systemic inflammation and oxidative stress. Overall, patients with COPD have a 2-3-fold increased risk of CVD as compared to age-matched controls when adjusted for tobacco smoking. Chronic heart failure (HF) is a frequent and important comorbidity which has a significant impact on prognosis in COPD, and vice versa. HF overlaps in symptoms and signs and has a common comorbidity with COPD, so that diagnosis of COPD is difficult in patients with HF. The combination of HF and COPD presents many therapeutic challenges including beta-blockers (BBs) and beta-agonists. Inhaled long-acting bronchodilators including beta2-agonists and anticholinergics for COPD would not worsen HF. Diuretics are relatively safe, and angiotensin-converting enzyme inhibitors are preferred to treat HF accompanied with COPD. BBs are only relatively contraindicated in asthma, but not in COPD. Low doses of cardioselective BBs should be aggressively initiated in clinically stable patients with HF accompanied with COPD combined with close monitoring for signs of airway obstruction and gradually up-titrated to the maximum tolerated dose. Encouraging appropriate and aggressive treatment for both HF and COPD should be recommended to improve quality of life and mortality in HF patients with COPD.


Nonclinical safety assessment of SPX-101, a novel peptide promoter of epithelial sodium channel internalization for the treatment of cystic fibrosis.
ENaC inhibition has long been an attractive therapeutic target for the treatment of cystic fibrosis. However, previous attempts at developing ENaC inhibitors have been unsuccessful due to complications arising from systemic circulation of the compounds. Here, we describe the preclinical toxicology assessment of a new inhaled peptide promoter of ENaC internalization delivered as a nebulized aerosol. Preclinical assessment of SPX-101 safety was determined using an in vitro hERG assay, bolus injection of SPX-101 in a canine cardiovascular and respiratory safety pharmacology model and 28-day inhalation toxicology studies of nebulized drug in rats and dogs. SPX101 had no effects on the respiratory, cardiac or central nervous systems. The 28-day inhalation toxicology studies of nebulized SPX-101 in rats and dogs revealed no drug-related adverse events. Plasma levels of SPX-101 peaked less than 1 h after the end of treatment in rats and were below the limit of detection in canine models. SPX-101, a novel peptide promoter of ENaC internalization, elicited no adverse effects at doses up to the MFD and in excess of the highest preclinical efficacious and expected clinical doses. In contrast to channel blockers like amiloride and derivative small molecules, SPX-101 does not achieve significant systemic circulation, thus doses are not limited due to toxic side effects like hyperkalemia and weight loss.


Open-source software for ultrasound-based guidance in spinal fusion surgery.
Spinal instrumentation and surgical manipulations may cause loss of navigation accuracy requiring an efficient re-alignment of the patient anatomy with pre-operative images during surgery. While intra-operative ultrasound (iUS) guidance has shown clear potential to reduce surgery time, compared with clinical computed tomography (CT) guidance, rapid registration aiming to correct for patient misalignment has not been addressed. In this article, we present an open-source platform for pedicle screw navigation using iUS imaging. The alignment method is based on rigid registration of CT to iUS vertebral images and has been designed for fast and fully automatic patient re-alignment in the operating room. Two steps are involved: first, we use the iUS probe's trajectory to achieve an initial coarse registration; then, the registration transform is refined by simultaneously optimizing gradient orientation alignment and mean of iUS intensities passing through the CT-defined posterior surface of the vertebra. We evaluated our approach on a lumbosacral section of a porcine cadaver with seven vertebral levels. We achieved a median target registration error of 1.47 mm (100% success rate, defined by a target registration error <2 mm) when applying the probe's trajectory initial alignment. The approach exhibited high robustness to partial visibility of the vertebra with success rates of 89.86% and 88.57% when missing either the left or right part of the vertebra and robustness to initial misalignments with a success rate of 83.14% for random starts within ±20° rotation and ±20 mm translation. Our graphics processing unit implementation achieves an efficient registration time under 8 s, which makes the approach suitable for clinical application.


Digital governance and its benchmarking college talent training under the rural revitalization in China-A case study of Yixian County (China).
Rural digital governance has been the favorite subject of social governance with the aim of sustainable development of rural revitalization. Therefore, an indicator system is constructed to evaluate its satisfaction in Yixian County (China) based on principal component analysis, multiple regression analysis, and SEM structural equation analysis. The study finds that (1) the four dominant observation indicators, namely, "satisfaction of participation," "satisfaction of diversification," "satisfaction of legal norms," and "satisfaction of technical support," have a significant impact on the satisfaction of rural digital governance, and there is a linkage effect among the four observation indicators; (2) in terms of the four potential variables, "value guidance satisfaction" (0.772), "regulatory constraint satisfaction" (0.756), "satisfaction of support guarantee," (0.699) and "multiple collaboration satisfaction" (0.676) have a decreasing influence on the overall satisfaction of rural digital governance, and there is much room for improvement. This study deepens the understanding of digital governance, and the following countermeasures are formed: strengthening the leading role of value concept; perfecting the constraint efficiency of "four governance" rule system; creating a new pattern of social "intelligent governance"; promoting the enabling effect of digital governance technology.


Bodyweight variability and the risk of psoriasis: a nationwide population-based cohort study.
Bodyweight variability has been suggested to exacerbate chronic inflammation and increase the risk of adverse cardiovascular events. Little is known whether high variability in bodyweight affects the development of psoriasis. To investigate the association between weight variability and the risk of psoriasis. Using a representative cohort enrolled in the national health examination programme conducted by the Korean National Health Insurance Service, 8 016 907 people who were free of psoriasis and who underwent at least three health examinations between 2010 and 2015 were followed until the end of 2017. We classified participants numerically according to the variability indices and defined high variability (Q4) as the highest quartile of variability. Cox proportional hazard regression models were used to evaluate the risk of psoriasis according to the quartile groups of bodyweight variability. In total, 187 128 (2.33%) participants developed psoriasis during a median follow-up of 3.4 years. There was an association between baseline body mass index and the risk of psoriasis. In the multivariable model adjusting for confounding variables, an incrementally increased risk of psoriasis was observed for higher quartiles compared with the lowest quartile group (Q1). The hazard ratio (HR) and 95% confidence intervals comparing the highest (Q4) and lowest quartiles (Q1) of bodyweight variability were 1.06 (1.05-1.07) for psoriasis. High bodyweight variability was significantly associated with an increased risk of psoriasis. These findings imply that clinicians should encourage patients to maintain proper bodyweight to help prevent psoriasis.


Transcriptional gene silencing requires dedicated interaction between HP1 protein Chp2 and chromatin remodeler Mit1.
Heterochromatin protein 1 (HP1) proteins are key factors of eukaryotic heterochromatin that coordinate chromatin compaction and transcriptional gene silencing. Through their multivalency they act as adaptors between histone H3 Lys9 di/trimethyl marks in chromatin and effector complexes that bind to the HP1 chromoshadow domain. Most organisms encode for multiple HP1 isoforms and the molecular mechanisms that underpin their diverse functions in genome regulation remain poorly understood. In fission yeast, the two HP1 proteins Chp2 and Swi6 assume distinct roles and Chp2 is tightly associated with the nucleosome remodeling and deacetylation complex SHREC. Here we show that Chp2 directly engages the SHREC nucleosome remodeler subunit Mit1. The crystal structure of the interaction interface reveals an extraordinarily extensive and specific interaction between the chromoshadow domain of Chp2 and the N terminus of Mit1. The integrity of this interface is critical for high affinity binding and for heterochromatin formation. Comparison with Swi6 shows that the Chp2-Mit1 interface is highly selective and thereby provides the molecular basis for the functional specialization of an HP1 isoform.


Developmental expression of glycine receptor subunits in rat cerebellum.
The distribution of the glycine receptor subunits alpha1-3 and beta in the developing rat cerebellum was studied from postnatal day 1 to adulthood by means of quantitative RT-PCR and immunohistochemistry. qRT-PCR of postnatal cerebella indicated the presence of mRNA for each subunit, with a relative expression of alpha2>alpha3>alpha1>beta. The immunohistochemistry indicated a strong alpha2 signal in the Purkinje cells, internal and external granular layers. The alpha1-3 subunits had weak signals in the Purkinje cells and molecular layer. The alpha1 subunit was expressed at a low level and was also found in the white matter. The function of these receptors in neuronal and glial plasma membranes in early postnatal development remains to be determined.


Retracted: Effects of Valsartan on LN, FN, MDA, Renal Tissue Fibrosis, and Inflammatory Infiltration in DN Rats.
[This retracts the article DOI: 10.1155/2022/6473393.].


A New Species of Demodex (Acariformes: Prostigmata) Observed in the Mouflon, Ovis aries musimon (Artiodactyla: Bovidae) with Data on the Parasitism and Occurrence of Other Ectoparasites.
A greater understanding of mite biodiversity and ecology can explain their preference for microhabitats within host bodies, i.e., as ecto-, meso-, and endoparasites. Similarly, learning about the patterns formed by mite communities in wild animals can shed light on the mechanisms of parasitosis development in their domesticated counterparts. Hence, the present study examined the acarofauna of the mouflon, introduced to Poland in the early 20th century from a region of endemic occurrence. Forty-one individuals were examined for the presence of ectoparasites between 2010 and 2013; later, skin fragments were analysed for the presence of skin mites. A new species of Demodecidae, Demodex musimonis sp. nov., was discovered in the skin of the pasterns of 14.6% mouflons, as well as the ectoparasitic tick Ixodes ricinus (prevalence 29.3%) and ungulate-typical fly Lipoptena cervi (34.1%). However, no mites typical for ovine Ovis (Psorergatidae, Psoroptidae) were noted, nor any colonisation of microhabitats by species from local ungulates, resulting from the loss of original parasites during the introduction. A comparison of the acarofauna of the mouflon and domestic sheep Ovis aries aries suggests that a mite community with a complex structure and the co-occurrence of different families may be formed. However, it is not known whether the acarofauna of domestic sheep is derived from wild ancestors or the process of domestication. Even so, the peculiar Demodecidae must have been part of the natural parasitofauna of wild sheep, of which only D. musimonis sp. nov. has been recognised so far.


Identification of novel ciliogenesis factors using a new in vivo model for mucociliary epithelial development.
Mucociliary epithelia are essential for homeostasis of many organs and consist of mucus-secreting goblet cells and ciliated cells. Here, we present the ciliated epidermis of Xenopus embryos as a facile model system for in vivo molecular studies of mucociliary epithelial development. Using an in situ hybridization-based approach, we identified numerous genes expressed differentially in mucus-secreting cells or in ciliated cells. Focusing on genes expressed in ciliated cells, we have identified new candidate ciliogenesis factors, including several not present in the current ciliome. We find that TTC25-GFP is localized to the base of cilia and to ciliary axonemes, and disruption of TTC25 function disrupts ciliogenesis. Mig12-GFP localizes very strongly to the base of cilia and confocal imaging of this construct allows for simple visualization of the planar polarity of basal bodies that underlies polarized ciliary beating. Knockdown of Mig12 disrupts ciliogenesis. Finally, we show that ciliogenesis factors identified in the Xenopus epidermis are required in the midline to facilitate neural tube closure. These results provide further evidence of a requirement for cilia in neural tube morphogenesis and suggest that genes identified in the Xenopus epidermis play broad roles in ciliogenesis. The suites of genes identified here will provide a foundation for future studies, and may also contribute to our understanding of pathological changes in mucociliary epithelia that accompany diseases such as asthma.


The Whitening of Brown Fat and Its Implications for Weight Management in Obesity.
Systemic inflammation resulting from dysfunction of white adipose tissue (WAT) accelerates the pathologies of diabetes and cardiovascular diseases. In contrast to WAT, brown adipose tissue (BAT) is abundant in mitochondria that produce heat by uncoupling respiratory chain process of ATP synthesis. Besides BAT's role in thermogenesis, accumulating evidence has shown that it is involved in regulating systemic metabolism. Studies have analyzed the "browning" processes of WAT as a means to combat obesity, whereas few studies have focused on the impact and molecular mechanisms that contribute to obesity-linked BAT dysfunction--a process that is associated with the "whitening" of this tissue. Compared to WAT, a dense vascular network is required to support the high energy consumption of BAT. Recently, vascular rarefaction was shown to be a significant causal factor in the whitening of BAT in mouse models. Vascular insufficiency leads to mitochondrial dysfunction and loss in BAT and contributes to systemic insulin resistance. These data suggest that BAT "whitening," resulting from vascular dysfunction, can impact obesity and obesity-linked diseases. Conversely, agents that promote BAT function could have utility in the treatment of these conditions.


COVID-19 infection and hospitalization rate in Iranian multiple sclerosis patients: What we know by May 2021.
Despite investigations on the effect of disease modifying therapies (DMTs) used in multiple sclerosis (MS) on coronavirus disease 2019 (COVID-19); there are still controversies. We designed this study to evaluate the epidemiological features of covid-19 in a large sample of people with MS (pwMS) in Isfahan, Iran, as well as the association between DMTs, risk of COVID-19 infection and hospitalization. In an observational pwMS, we interviewed subjects on their MS and COVID-19 history. 3050 subjects were included (74% female) with a mean age of 41.36. 423 (13.8%) had confirmed COVID-19 which shows that pwMS are at a higher risk of infection compared to the general population, No significant relationship was observed in COVID-19 infection when individual drugs. Dimethyl fumarate and rituximab had the lowest and the highest relative risks for hospitalization rate compared to other drugs, respectively. We found no evidence supporting a higher prevalence of COVID-19 in pwMS compared to the general population. However, our results show pwMS to be more prone to hospitalization compared to the general population, Therefore, it is advised to use safer treatment if possible until complete vaccination, and to postpone the use of rituximab.


The problem of subepidermal blisters in neoformed integuments.
The present paper is a review of articles on the onset of subepidermal blisters in neoformed integuments. Considering the discrepancy between the literature data and our clinical experience concerning spontaneous onset of subepidermal blisters in neoformed integuments, we decided to conduct an extensive review of the literature. The main finding arising from it was the lack of characterization of the neoformed integument where the blisters were formed. These were normally referred to only by clinical descriptions such as "spontaneously healed burn", "grafted site", "donor site", "epidermal graft". Anatomical and clinical pathology aspects such as the formation mechanism of these integuments and the respective tissues that comprise them were not considered. We concluded that by adopting more precise criteria to classify neoformed integuments we would realize that split thickness grafts are not susceptible to blister formation.


Brachytherapy for targeting the immune system in cervical cancer patients.
New combinations based on standard therapeutic modalities and immunotherapy require understanding the immunomodulatory properties of traditional treatments. The objective was to evaluate the impact of brachytherapy (BT) on the immune system of cervical cancer and to identify the best modality, High-dose-rate brachytherapy (HDR-BT) vs. Pulsed-dose-rate (PDR-BT), to target it. Nineteen patients enrolled in a prospective study received chemoradiation (CRT) and subsequently HDR-BT or PDR-BT. Peripheral blood samples were obtained for immunophenotyping analysis by flow-cytometry before CRT, BT, and two and four weeks after BT. The Friedman one-way ANOVA, Conover post hoc test, and the Wilcoxon signed-rank test were used to compare changes in cell populations at different periods, perform multiple pairwise comparisons and assess differences between treatment groups (PDR and HDR). Natural killer cells (NKs) were the best target for BT. Patients receiving HDR-BT achieved significantly higher values and longer time of the CD56dimCD16 + NK cells with greater cytotoxic capacity than the PDR-BT group, which presented their highest elevation of CD56-CD16 + NK cells. Furthermore, both BT modalities were associated with an increase in myeloid-derived suppressor cells (MDSCs), related to a worse clinical prognosis. However, there was a decrease in the percentage of CD4 + CD25 + Foxp3 + CD45RA + regulatory T cells (Tregs) in patients receiving HDR-BT, although there were no significant differences between BT. Immune biomarkers are important predictive determinants in cervical cancer. Higher cytotoxic NK cells and a trend toward lower values of Tregs might support the use of HDR-BT to the detriment of PDR-BT and help develop effective combinations with immunotherapy.


Predictors of mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis.
Better insight in patients' prognosis can help physicians to timely initiate advance care planning (ACP) discussions with patients with chronic obstructive pulmonary disease (COPD). We aimed to identify predictors of mortality. We systematically searched databases Embase, PubMed, MEDLINE, Web of Science, and Cochrane Central in April 2020. Papers reporting on predictors or prognostic models for mortality at 3 months and up to 24 months were assessed on risk-of-bias. We performed a meta-analysis with a fixed or random-effects model, and evaluated the discriminative ability of multivariable prognostic models. We included 42 studies (49-418,251 patients); 18 studies were included in the meta-analysis. Significant predictors of mortality within 3-24 months in the random-effects model were: previous hospitalization for acute exacerbation (hazard ratio [HR] 1.97; 95% confidence interval [CI] 1.32-2.95), hospital readmission within 30 days (HR 5.01; 95% CI 2.16-11.63), cardiovascular comorbidity (HR 1.89; 95% CI 1.25-2.87), age (HR 1.48; 95% CI 1.38-1.59), male sex (HR 1.68; 95% CI 1.38-1.59), and long-term oxygen therapy (HR 1.74; 95% CI 1.10-2.73). Nineteen previously developed multicomponent prognostic models, as examined in 11 studies, mostly had moderate discriminate ability. Identified predictors of mortality may aid physicians in selecting COPD patients who may benefit from ACP. However, better discriminative ability of prognostic models or development of a new prognostic model is needed for further large-scale implementation. PROSPERO (CRD42016038494), https://www.crd.york.ac.uk/prospero/ .


Peripheral rheumatoid ulceration and evidence for conjunctival collagenase production.
Two patients with rheumatoid arthritis and peripheral corneal ulcerations were successfully treated by conjunctival resection. The tissues removed were assayed by a variation of the radial diffusion method for tissue collagenases. We used an agarose matrix containing lathyritic rat skin collagen. Wells 3 mm deep were punched in the agarose-collagen and surgical specimens were placed in the wells. Spaces remaining in the wells were filled with balanced salt solution. The assay dishes were incubated for four days at 32 degrees C near 100% humidity. Under these conditions release of collagenase was detected by the clearing of diffuse zones in the gel surrounding the well. Conjunctiva proximal to the ulcer produced definite zones of lysis, whereas control specimens taken remote to the ulceration produced no lysis. This direct evidence for collagenase involvement offers an exploration for the beneficial effects of conjunctival resection.


Loneliness among adolescents and young adults with cancer during the COVID-19 pandemic: a cross-sectional survey.
Adolescents and young adults (AYAs) diagnosed with cancer are at an increased risk of experiencing social isolation and loneliness secondary to their cancer and its treatment. The physical distancing measures implemented during the COVID-19 pandemic may have further increased loneliness among this group. This study examined the prevalence of loneliness and factors associated with loneliness among AYAs with cancer during this pandemic. We conducted a self-administered, online, cross-sectional survey of Canadian AYAs diagnosed with cancer between 15 and 39 between January and February 2021. Loneliness was measured using the 3-item UCLA Loneliness Scale. Factors associated with higher levels of loneliness were identified using multiple logistic regression. The analysis included 805 AYAs. The prevalence of loneliness was 52.2% [N = 419, 95% CI (confidence interval) 48.7 to 55.6%]. Individuals who were 18-25 years old [AOR (adjusted odds ratio)1.60, CI 1.03-2.47, p = 0.035], currently undergoing cancer therapy (AOR 1.46, 95% CI 1.03-2.07, p = 0.035), who self-disclosed the presence of a pre-pandemic mental health condition (AOR 2.09, 95% CI = 1.22-3.58, p = 0.007), or were not in a relationship (AOR 2.22, 95% CI 1.57-3.14, p < 0.001) were more likely to report loneliness than others. Participants that lived in rural or remote locations were less likely to experience loneliness (AOR 0.59, 95%CI 0.40-0.87, p = 0.008). One in two AYAs with cancer are feeling lonely during the COVID-19 pandemic. Future studies for developing interventions to target loneliness, particularly for those at greater risk, are necessary to improve the health and quality of life of AYAs with cancer.


Impact of support media in an integrated biofilter-submerged membrane system.
The impact of a support material on an integrated biofilter-membrane system, simulating a difficult-to-treat surface water, was examined in terms of membrane fouling rate and water quality parameters. The support media in the membrane tanks did not generally affect any of the water quality parameters measured; however, there was an observable difference in the membrane fouling rates between the two processes with the support media system fouling at least two times slower than the non-support system. Total organic carbon (TOC) removals at around 60% were observed for two integrated biofilter-immersed membrane processes with the majority of the TOC removal occurring in the biofilters. One of the membrane tanks contained a support media (Process A) while the other did not (Process B). The feedwater contained humic acid (65% w/w) and readily biodegradable carbons (35% w/w) in the forms of acetic acid, formic acid and formaldehyde. The influent TOC values were between 3.35 and 3.94 mg/L. Acetate removals varied between 66 and 83%, while over 90% of the formate was removed and the formaldehyde was completely removed in the biofilters. There was a decrease in the UV absorbance values by over 70% for both processes.


Prevalence and risk factors for laminitis within the Norwegian pony breed Nordlandshest/Lyngshest.
Laminitis is a systemic condition resulting in debilitating pain and structural changes within the feet, and hence has major welfare implications. Causes include endocrine and systemic inflammatory conditions. Ponies are frequently affected, and observations in the field suggest that occurrence of laminitis is also common in Norwegian breeds. The aim of this study was to estimate the prevalence and risk factors for laminitis within the Norwegian pony breed Nordlandshest/Lyngshest. The study was a cross-sectional study based on questionnaires sent to members of the Norwegian Nordlandshest/Lyngshest breed association. Questionnaires were received for 504 animals, of which 464 records were eligible and included in analyses. The population comprised 71 stallions, 156 geldings, and 237 mares, with an age between 1 and 40 years (median and interquartile ranges: 12 (6-18) years). The estimated 3-year period prevalence of laminitis was 8.4% (95% confidence interval (CI95): 6.0-11.3%), whereas lifetime prevalence was 12.5% (CI95: 9.6-15.9%). Mares had a significantly higher period- and lifetime prevalence of laminitis than male horses, and horses 10 years and older had a significantly higher prevalence than younger horses. The lifetime prevalence of laminitis was 3.2% in horses 9 years and younger, whereas from 17.3-20.5% in older horses. Multivariable logistic regression analysis identified age, sex, and regional adiposity as significantly (P < 0.05) associated with the 3-year period outcome of laminitis: Horses older than 9 years had a three-fold increase in the likelihood of having laminitis compared to the younger horses (Odds Ratio (OR)10-14 years = 3.37 (CI95 = 1.19-9.50), OR15-19 years = 3.06 (CI95 = 1.04-9.05), and OR>20 years = 2.70 (CI95 = 0.90-8.02). Mares were more than twice as likely (OR = 2.44 (CI95 = 1.17-5.12) to have laminitis compared to male horses, and horses with regional adiposity had increased odds (OR = 2.35 (CI95 = 1.15-4.82) of laminitis compared to horses without regional adiposity. Laminitis appears to be a considerable welfare issue in the Norwegian pony breed Nordlandshest/Lyngshest. The identified risk factors age, sex, and regional adiposity highlight the need for improved owner education and awareness of strategies to reduce laminitis risk.


Anxiety following miscarriage and the subsequent pregnancy: a review of the literature and future directions.
This is the first comprehensive review to summarize the research literature regarding anxiety symptomatology and disorders following miscarriage. Both "controlled" and "uncontrolled" designs are considered, with the inferential limitations of studies lacking comparison groups highlighted. The limited research available suggests that miscarrying women are at increased risk for anxiety symptoms immediately following miscarriage and continuing until approximately 4 months post-loss. Beyond 4 months, reports are inconsistent. There is evidence to suggest increased risk for some anxiety disorders in the 6 months following loss; however, studies using larger sample sizes and comparison groups are needed. This is the first review to consider the incidence of anxiety disorders following miscarriage, as well as the psychological impact of loss on the pregnancy subsequent to miscarriage, and the impact on partners of miscarrying women. Areas warranting further study are noted and are intended to guide future investigation.


Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain dopamine neurons in vivo.
Midbrain dopamine neurons in vivo discharge in a single-spike firing pattern or in a burst-firing pattern. Such activity in vivo strikingly contrasts with the pacemaker activity of the same dopamine neurons recorded in vitro. We have recently shown that burst activity in vivo of midbrain dopamine neurons is due to the local activation of excitatory amino acid receptors, as microapplication of the broad-spectrum antagonist of excitatory amino acids, kynurenic acid, strongly regularized the spontaneous firing pattern of these dopamine neurons. In the present study, we investigated which subtypes of excitatory amino acid receptors are involved in the burst-firing of midbrain dopamine neurons in chloral hydrate-anaesthetized rats, iontophoretic or pressure microejections of 6-cyano, 7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter the spontaneous burst firing of dopamine neurons (n = 36). In contrast, similar ejections of (+-)2-amino,5-phosphonopentanoic acid (AP-5), a specific antagonist at NMDA receptors, markedly regularized the firing pattern by reducing the occurrence of bursts (n = 52). In addition, iontophoretic ejections of NMDA, but not kainate or quisqualate, elicited a discharge of these dopamine neurons in bursts (n = 20, 12 and 14, respectively). These data suggest that burst-firing of midbrain dopamine neurons in vivo results from the tonic activation of NMDA receptors by endogenous excitatory amino acids. In view of the critical dependency of catecholamine release on the discharge pattern of source neurons, excitatory amino acid inputs to midbrain dopamine neurons may constitute a major physiological substrate in the control of the dopamine level in target areas.


Penetrating injury with an arrow impacted in the neck in rural Tanzania, a case report.
Penetrating neck injuries refer to neck injuries that penetrate through the platysma layer which can cause life-threatening injuries to the aerodigestive and neurovascular systems. Currently penetrating neck injuries are mainly due to modern firearms however penetrating neck injuries due to arrows are still seen, although rare, in rural areas among developing countries. Management depends on hemodynamic stability, signs of structural damage and zone of neck involved. 19-year-old male presenting with a penetrating arrow impacted in his neck following an attack by cattle raiders who was otherwise stable of presentation. Underwent preoperative imaging with removal of the arrow under general anaesthesia via surgical exploration. We concur with the recommendation to first obtain adequate imaging to establish degree of injury as well as for operative planning. Removal of impacted arrow should not be carried out blindly but rather in a controlled environment under general anaesthesia via surgical exploration. Penetrative arrow injuries to the neck are an archaic problem that can be dealt with via modern surgical principles towards penetrating neck injuries. Unstable patients warrant emergent exploration however stable patients can first be worked up appropriately to ascertain degree of injury. Impacted arrows can then be removed safely under general anaesthesia rather than risk further injury to critical structures via blind removal.


Predisposing factors for seroma formation in patients undergoing thyroidectomy: Cross-sectional study.
Seroma is defined as collection of fluid within the surgical site during postoperative period that causes several complications. Recognition of predisposing risk factors can lead to avoid seroma formation after thyroidectomy. A cross-sectional study was carried out during a 3-year period and 678 patients were enrolled the study. We recorded demographic data, past medical history and the type of thyroidectomy were for all patients. We measured total and ionized serum calcium and albumin level in all patients before surgery and a day after it. All patients underwent total or subtotal thyroidectomy and if needed central neck dissection was performed subsequently. Patients underwent serial aspiration If they had seroma formation. The overall post-thyroidectomy seroma incidence was 2.2%. There was no statistically significant correlation while evaluating gender, age and body mass index with post-operative seroma formation. However, seroma formation was significantly higher in patients underwent total thyroidectomy (P = 0.041). The results of postoperative laboratory tests showed a significant lower level of ionized calcium in patients with seroma formation (P < 0.0001). Logistic regression showed statistically significant value for variables including age, BMI and decreased ionized calcium level, in developing of seroma. We showed that Seroma formation was lower during thyroidectomy via electrical vessel sealing system in comparison with previous studies. In our study, older age, greater body mass index and decreased ionized calcium level were predictors of seroma formation.


A selective Ru-catalyzed semireduction of alkynes to Z olefins under transfer-hydrogenation conditions.
By using a readily available, air- and moisture-stable dihydrido-Ru complex, a variety of Z olefins are accessible under transfer-hydrogenation conditions with formic acid as the hydrogen source in excellent yields and Z/E selectivities.


[The use of the expanded PTFE (Gore-Tex) prosthesis with progressive preoperative pneumoperitoneum in the repair of massive inguinal hernias and large laparoceles].
The authors present two cases of massive inguinal hernia and large recurring abdominal wall defect, in which hernia repair and wall reconstruction is made possible thanks to the use of large patches of expanded PTFE (Gore-Tex). The authors moreover insist on the efficacy of using the progressive preoperative pneumoperitoneum as a technic to prepare the patient to surgery together with respiratory physiotherapy, for the purpose of preventing the occurrence of unfavourable repercussions falling upon the cardiorespiratory apparatus with the repositioning into the abdomen of the hernias.


Hyperpolarization transfer pathways in inorganic materials.
Dynamic nuclear polarization can be used to hyperpolarize the bulk of proton-free inorganic materials in magic angle spinning NMR experiments. The hyperpolarization is generated on the surface of the material with incipient wetness impregnation and from there it is propagated towards the bulk through homonuclear spin diffusion between weakly magnetic nuclei. This method can provide significant gains in sensitivity for MAS NMR spectra of bulk inorganic compounds, but the pathways of the magnetization transfer into the material have not previously been elucidated. Here we show how two-dimensional experiments can be used to study spin diffusion from the surface of a material towards the bulk. We find that hyperpolarization can be efficiently relayed from surface sites to multiple bulk sites simultaneously, and that the bulk sites also engage in rapid polarization exchange between themselves. We also show evidence that the surface peaks can exchange polarization between different sites in cases of disorder.


[Optic, scanning and transmission electron microscopic observations of synthetic fibers implanted in rabbit skin].
Artificial hair made of synthetic leacryl fibre was inserted into the skin of a rabbit in order to evaluate the biocompatibility of the insertion of heterologous material. On the 7th and 30th day following insertion, samples were taken from the areas involved and were observed by MO, TEM and SEM studies. Granuloma in both the early stage (7th day) and later at 30 days was evidenced and found to develop to cicatricial sclerosis.


Heat generation during removal of an abutment screw fragment from dental implants.
Little information is available on the effect of drilling speed on surrounding bone during the removal of an abutment screw fragment. The purpose of this in vitro study was to compare, in vitro, the peak temperature increase during the removal of fractured abutment screws from implants placed in a porcine mandible, using drilling speeds of 600 or 2000 rpm. Twenty 4.3×13-mm dental implants were placed in 10 dissected porcine mandibles: 2 implants per mandible, 1 on each side. Localized defects were created in 20 surface-treated abutment screws, which were then tightened into each implant until a reproducible fracture occurred in each screw. The fractured screws were removed with a handpiece removal kit and irrigated with room-temperature water at either 600 or 2000 rpm. The temperature rise at the implant surface was measured at 3 levels with 3 type-K thermocouples. Repeated measure ANOVA was performed with the Tukey-Kramer post hoc test for mean pair-wise comparisons (α=.05 for all tests). Mean peak temperatures were significantly higher at 2000 rpm than at 600 rpm in the mid-body (P<.001) and crestal (P=.003) regions but not in the apical (P=.225) implant locations. No significant differences in mean peak temperatures were found among the 3 locations using 600 rpm (P=.179). In the 2000-rpm group, mean peak temperature in the mid-body area was consistently higher than that in the apical (P<.001) area, and more instances of temperature rise above 56°C and 60°C were observed. In 1 implant from this group, the estimated peak temperature exceeded the bone damage threshold value (50°C for 30 seconds). A drilling speed of 2000 rpm during the removal of abutment screw fragments caused overheating of the outer surface of the implant which may damage the surrounding bone; a speed of 600 rpm appears to be safe.


Significant others and gambling treatment outcomes.
This study investigates the effect of significant others on treatment outcomes among treated pathological gamblers. This is a cohort study of individuals who received gambling treatment. Oregon Problem Gambling Services (OPGS) for gamblers and their family members. 4,410 adult gamblers who were discharged from treatment between August, 2001 and April, 2007. OPGS enrollment forms provided gambler gender, age, ethnicity, education level, employment status, gambling-related debt, and whether the gambler had a significant other at the time of enrollment. Termination forms provided information on the type of discharge (successful/unsuccessful) and treatment length (in days). Participation of the gambler's significant other in the family treatment program was identified. Results showed that age, ethnicity, gambling debt, and having a significant other are associated with the odds of successful treatment. Education level moderates the effect of having a significant other on treatment success. Age, ethnicity, education, employment, and having a significant other participate in treatment significantly impacted gamblers' length in treatment. These findings indicate that there may be a benefit to integrating significant others in gambling treatment methods. Significant others may act as social supports for gamblers seeking treatment, and involving loved ones in gambling treatment models may positively affect gambler treatment outcomes.


[The management of risks by the global risk analysis].
After a reminder on the fundamental concepts of the management of risk, the author describes the overall analysis of risk (AGR), name given by the author to the up-to-date APR method which after several changes of the initial process aims to cover a perimeter of analysis and broader management both at the level of structural that business risks of any kind throughout the system development life cycle, of the study of its feasibility to dismantling.


The crystal structure of leucyl-tRNA synthetase complexed with tRNALeu in the post-transfer-editing conformation.
Leucyl-tRNA synthetase (LeuRS) has a specific post-transfer editing activity directed against mischarged isoleucine and similar noncognate amino acids. We describe the post-transfer-editing and product complexes of Thermus thermophilus LeuRS (LeuRSTT) with tRNA(Leu) at 2.9- to 3.3-A resolution. In the post-transfer-editing configuration, A76 binds in the editing active site exactly as previously found for the adenosine moiety of a small-molecule editing-substrate analog. The 60 C-terminal residues of LeuRSTT, unseen in previous structures, fold into a compact domain flexibly linked to the rest of the molecule and interacting with the G19-C56 tertiary base pair of tRNA(Leu). LeuRS recognition of tRNA(Leu) depends essentially on tRNA shape rather than base-specific interactions. The structures show that considerable domain rotations, notably of the editing domain, accompany the tRNA-3' end dynamics associated successively with aminoacylation, post-transfer editing and product release.


Spontaneous cholecystocutaneous fistula.
An external biliary fistula is a rare complication of gallstone disease. We present a case of cholecystocutaneous fistula successfully treated with excision and cholecystectomy. A 67-year-old man presented with a persisting discharge from what was thought to be an'abscess' in the right hypochondrium, which had previously been incised and drained. Investigation with computed tomography, ultrasound scanning and sinography demonstrated a cholecystocutaneous fistula and calculous cholecystitis. The fistulous track was excised together with the gallbladder. This condition is rarely seen nowadays due to the greater availability of antibiotic therapy and biliary surgery. Cholecystectomy is the preferred treatment, although in a few patients, the fistula may close spontaneously.


Dietary n-3 fatty acids and children with hyperlipidaemia.
A review of the literature shows that no studies on children with primary genetic lipid disorders have been published. Case reports are presented indicating that hyperlipidaemias presenting in children--both familial hypercholestrolaemia and disorders with secondary hyperlipidaemia (triglycerides) may benefit of the intake of n-3 fatty acids.


Elevated postprandial triglyceride-rich lipoproteins in patients with diabetes and stable coronary artery disease correlated with early renal damage and systemic inflammation.
Dyslipidaemia is key in the development of coronary heart disease (CHD) in patients with diabetes mellitus (DM). Accumulated evidence supports that diabetic nephropathy increases the mortality risk of patients with CHD, while the influence of diabetic dyslipidaemia on renal damage in patients with DM and CHD remains unknown. Moreover, recent data indicate that postprandial dyslipidaemia has predictive value in terms of CHD prognosis, especially in patients with DM. The study aimed to determine the relationship of triglyceride-rich lipoproteins (TRLs) after daily Chinese breakfast on systemic inflammation and early renal damage in Chinese patients with DM and SCAD. Patients with DM diagnosed with SCAD while in the Department of Cardiology of Shengjing Hospital from September 2016 to February 2017 were enrolled in this study. Fasting and 4-h postprandial blood lipids, fasting blood glucose, glycated haemoglobin, urinary albumin-to-creatinine ratio (UACR), serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) concentrations, and other parameters were measured. Fasting and postprandial blood lipid profiles and inflammatory cytokines were analysed using a paired t-test. The association between variables was analysed using Pearson or Spearman bivariate analysis. P < 0.05 was considered to be statistically significant. The study enrolled 44 patients in total. Compared with fasting state, postprandial total cholesterol high-density lipoprotein-cholesterol (HDL-C),low-density lipoprotein-cholesterol (LDL-C) and non-high-density lipoprotein-cholesterol (non-HDL-C) all showed no significant change. Postprandial serum triglyceride (TG) concentration increased significantly compared with that at fasting (1.40 ± 0.40 vs. 2.10 ± 0.94 mmol/L, P < 0.001), as did serum remnant lipoprotein-cholesterol (RLP-C) (0.54 ± 0.18 mmol/L vs. 0.64 ± 0.25 mmol/L). Pearson analysis revealed that serum TG and RLP-C positively correlated before and after breakfast. Moreover, during fasting, positive correlations were observed between TG and serum IL-6, TNF-α, and UACR. Positive correlations were observed between RLP-C and IL-6, UACR under fasting condition, while both TG and RLP-C were positively correlated with postprandial serum IL-6, TNF-α, and UACR concentrations. Finally, positive correlations were observed between UACR and IL-6 and TNF-α concentration under both fasting and postprandial conditions. An increase in postprandial TRLs was observed in Chinese patients with DM and SCAD after daily breakfast, and this increase may be related to early renal injury via the induction of systemic inflammation.


Connectivity from ipsilateral and contralateral dorsolateral prefrontal cortex to the active primary motor cortex during approaching-avoiding behavior.
Automatic action tendency is reflected by a fast reaction to approach positive stimulus and to avoid negative stimulus (automatic behaviors), while a slow reaction to approach negative stimulus and avoid positive stimulus (controlled behaviors). The dorsolateral prefrontal cortex (DLPFC) is involved in the modulation of the automatic action tendency; however, it remains unclear whether DLPFC modulates the behavior through motor inhibition or excitation, as well as the exact timing of the modulation. We used paired-pulse, dual-site TMS protocols to investigate the connectivity between left/right DLPFC and the left primary motor cortex (M1) during the manikin task performed with the right hand. For the behavioral data, the results from reaction time (RT) and premotor time (PMT), which represents the beginning of finger movements, of the approaching-avoiding behavior in both experiments showed a shorter duration for automatic behavior compared to the controlled behavior. There was stronger facilitation of the left DLPFC-left M1 connectivity at interstimulus-interval of 25 ms in controlled behavior compared to automatic behavior (positive-approaching vs. positive-avoiding: P = .002; negative-avoiding vs. negative-approaching: P = .017). The right DLPFC-left M1 connectivity did not change with the task. The present study confirmed the automatic action tendency from both reaction time and the premotor time. During the right-handed task, the DLPFC contralateral but not ipsilateral to the effector could facilitate the left M1 to speed up the execution of the controlled behavior through a polysynaptic pathway.


Global DNA methylation: uncommon event in oral lichenoid disease.
Accumulating evidence indicates that aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. The aim of this study was to perform the first wide DNA methylation study in OLD in order to investigate the relevance of DNA methylation changes in this premalignant disorder. Two different Illumina microarray platforms, namely the GoldenGate Cancer Panel I and the HumanMethylation27 DNA Analysis BeadChip, were utilized in the discovery phase to interrogate the methylation profile of 59 OLD cases and 9 healthy individuals. Top-ranked genes were further validated by pyrosequencing in a second sample set consisting of 160 OLD and 65 controls. Our results show that the frequency of aberrant DNA methylation is rare in OLD, and this finding was further corroborated by pyrosequencing in the biological validation. These findings reinforce the notion that molecular alterations associated with oral carcinogenesis do not seem to be common events in OLD, which in turn might explain the low rate of malignization of this disorder.


Ultrasound stimulation induces microRNA expression changes that could be involved in sonication-induced apoptosis.
The purpose of this study is to investigate the involvement of microRNAs (miRNAs) in sonication-induced apoptosis. U937 cells derived from human leukemia were sonicated with 1-MHz ultrasound at 0.4 W/cm(2) and 10 % duty factor for 60 s, a condition inducing apoptosis. The total RNA was extracted from cells at various timings after sonication and subjected to microarray and real-time PCR for miRNA expression analyses. Expression of several miRNAs was significantly affected by sonication. For miR-424* and miR-720, whose expressions were eminently decreased by sonication, cell lines overexpressing these miRNAs were established. Conversely, for miR-663B and miR-663, whose expressions were eminently increased by sonication, cell lines inhibiting these miRNA functions were established. When these cell lines were sonicated, a cell line inhibiting miR-663B function significantly increased sonication-induced apoptosis, suggesting this may be involved in cellular responses to sonication. Two genes that could induce apoptosis, KSR2 and CREBZF, were identified as potential target genes of miR-663B since potential target sequences on their 3' UTR mediated to decrease expression of a reporter gene. These results suggest that miRNAs may be involved in cellular responses to ultrasound through their expression changes caused by sonication.


Determination of underivatized amino acids to evaluate quality of beer by capillary electrophoresis with online sweeping technique.
Capillary electrophoresis (CE) with ultraviolet detection was applied to determine underivatized amino acids in beer, based on the coordination interaction of copper ions and amino acids. An online sweeping technique was combined with CE to improve detection sensitivity. Using the United Nations Food Agriculture Organization/World Health Organization model of essential amino acid pattern and flavor of amino acids, the quality and taste in three kinds of beer were evaluated. It was found that Beer2 had higher quality than the other two kinds and the content of phenylalanine, proline, serine, and isoleucine was relatively large in all three kinds of beers with a great influence on beer flavor. Optimal conditions for separation were as follows: 50mM CuSO4 at pH 4.40 as buffer; total length of fused silica capillary, 73 cm; effective length, 65 cm; separation voltage, 22.5 kV; and optimized sweeping condition, 70 seconds. In the appropriate range, linearity (r2 > 0.9989), precision with a relative standard deviation < 8.05% (n = 5), limits of detection (0.13-0.25 μg/mL), limit of quantification (0.43-0.83 μg/mL), and recovery (80.5-115.8%) were measured. This method was shown to be applicable to the separation of amino acids in beer and to perform quantitative analysis directly without derivatization for the first time.


In vitro bloodbrain barrier permeability study of four main active ingredients from Alpiniae oxyphyllae fructus.
The fruits of Alpinia oxyphylla Miq., a broadly utilized traditional Chinese medicine, have a number of effects on the central nervous system (CNS). The main active constituents of Alpiniae oxyphyllae fructus (AOF) were nootkatone, tectochrysin, chrysin and protocatechuic acid. An immortalized human brain microvascular endothelial cell (hCMEC/D3) and astrocyte (HA1800) coculture model was used to investigate the permeability of the blood-brain barrier (BBB). The validation of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) methods for the four compounds was conducted following industry guidelines. Calibration curves were generated with mean coefficients (R2) better than 0.99. The inter-day and intra-day precisions were less than 8.53% and 7.12%, respectively. The accuracies were lower than ± 11.57%, and recoveries were greater than 86.07%. The samples of the transport experiment were examined, and the apparent permeability coefficients (Papp) were calculated. The efflux ratios of the four compounds are all less than 2. The Papp values of protocatechuic acid, chrysin, nootkatone, tectochrysin were at the level of 10-5, 10-6, 10-6, and 10-7 cm/s, respectively. All four compounds crossed the BBB by passive diffusion, with protocatechuic acid having high permeability, and tectochrysin having poor permeability. This research indicated the permeability of protocatechuic acid, chrysin, nootkatone and tectochrysin through the BBB and offered a foundation for related research on AOF in the treatment of CNS illnesses.


Functional Mutations in the microRNA-155 Promoter Modulate its Transcription Efficiency and Expression.
Limited research has been conducted on porcine miR-155 promoters, and previous study from our group have identified two haplotypes (TT and CC) in different pig breeds, each associated with five fully linked mutation sites within or near the miR-155 gene (Li et al. Dev Comp Immunol 39(1):110-116, 2013). In this study, the promoter region of porcine miR-155 was screened, and two important transcription factors, Foxp3 and RelA, were identified. The binding ability of Foxp3 protein was found to be affected by the first mutation site (A/C) using EMSA analysis. In vitro experiments revealed that the expression level of miR-155 was significantly higher in the C haplotype compared to the T haplotype. Additionally, northern blotting assays indicated that both the first mutation site (A/C) and the fourth mutation site (G/T) had a significant impact on miR-155 expression levels. These findings provide further insights into the transcriptional regulation of porcine miR-155 and identify crucial mutation sites that influence miR-155 expression. This knowledge can serve as a basis for identifying potential molecular markers associated with disease resistance in swine.


Association of obesity with disease outcome in multiple sclerosis.
Obesity reportedly increases the risk for developing multiple sclerosis (MS), but little is known about its association with disability accumulation. This nationwide longitudinal cohort study included 1066 individuals with newly diagnosed MS from the German National MS cohort. Expanded Disability Status Scale (EDSS) scores, relapse rates, MRI findings and choice of immunotherapy were compared at baseline and at years 2, 4 and 6 between obese (body mass index, BMI ≥30 kg/m2) and non-obese (BMI <30 kg/m2) patients and correlated with individual BMI values. Presence of obesity at disease onset was associated with higher disability at baseline and at 2, 4 and 6 years of follow-up (p<0.001). Median time to reach EDSS 3 was 0.99 years for patients with BMI ≥30 kg/m2 and 1.46 years for non-obese patients. Risk to reach EDSS 3 over 6 years was significantly increased in patients with BMI ≥30 kg/m2 compared with patients with BMI <30 kg/m2 after adjustment for sex, age, smoking (HR 1.87; 95% CI 1.3 to 2.6; log-rank test p<0.001) and independent of disease-modifying therapies. Obesity was not significantly associated with higher relapse rates, increased number of contrast-enhancing MRI lesions or higher MRI T2 lesion burden over 6 years of follow-up. Obesity in newly diagnosed patients with MS is associated with higher disease severity and poorer outcome. Obesity management could improve clinical outcome of MS.


Quantitation of the reticuloendothelial system clearance of soluble fibrin.
Phagocytosis of particulate fibrin has been previously established as a function of the reticuloendothelial system (RES). More recently, reticuloendothelial cells have been shown to bind soluble fibrin/fibrinogen (f/F) complexes in vitro. To quantitate RES clearance vs microthrombus formation, varying doses (0.1-6 mg/kg) of 125I-soluble f/F was injected into rabbits. One hour later the animals were killed, at which time 48 +/- 8% of the 125I f/F had been cleared from the blood. Homogenized organ samples were separated into insoluble pellet, soluble protein bound, and free 125I. Treatment of other samples with plasmin prior to homogenization differentiated the insoluble 125I into RES cleared (intracellular-plasmin resistant) vs microthrombi (plasmin sensitive pellet 125I). 125I-f/F was chiefly found in liver and spleen. Injection of low f/F concentrations resulted in no plasmin sensitive pellet 125I. 3 mg/kg f/F caused small, variable amounts of plasmin sensitive pellet 125I, chiefly in the kidney. With 6 mg/kg, 21-50% of the insoluble 125I in all organs was plasmin sensitive, and occasional 1-2 mm thrombi were found. The data indicate complete and rapid RES clearance of small amounts of soluble f/F from the blood, without microthrombi being formed. The RES was acutely saturated at 1.5-3.0 mg f/F/kg, which is equivalent to immediate conversion to fibrin of 1-2% of the intravascular fibrinogen pool.


The effect of proximity to protected areas on community adaptation to environmental change.
The consequences of protected areas for proximal human communities are diverse. Protected areas can alleviate poverty by providing a range of economic opportunities for people that live and work within them. Equally, however, they may also disempower and disposes local communities. For communities adapting to systemic environmental change, proximity to protected areas can act to limit potential adaptive pathways. Here, we employ social science methods to explore the impact of an internationally significant protected area on adjacent communities in the Tonle Sap Lake basin, Cambodia. Semi-structured interviews, informed by a scenario framework, reveal an awareness of declining fish yields and a perceived lack of economic alternatives. Vulnerability to hydroclimatic extremes, particularly storms, flood, drought and - increasingly - fire, are exacerbated as a result of proximity to the protected area. We conclude that the impact of protected areas on local communities is heterogenous, and that the development of adaptive and effective management policies requires sensitivity to local conditions and impacts.


Nicorandil inhibits neutrophil recruitment in carrageenan-induced experimental pleurisy in mice.
Nicorandil is a drug characterized by the coupling of a nitric oxide (NO) donor to nicotinamide. We have previously demonstrated that nicotinamide exhibits activity in different models of pain and inflammation. Now, we investigated the effects induced by per os (p.o.) administration of nicorandil (25, 50 or 100mg/Kg) on neutrophil recruitment in a carrageenan-induced model of pleurisy in mice. Effects induced by nicorandil (100mg/kg) were compared with those induced by equimolar doses of nicotinamide (58mg/kg) and N-(2-hydroxyethyl)-nicotinamide (NHN; 79mg/kg). We also investigated whether effects on the production of inflammatory mediators play a role in the activity of nicorandil. P.o. nicorandil, 0.5h before and 1h after the i.pl. injection of carrageenan, reduced neutrophil recruitment. However, equimolar doses of nicotinamide or NHN failed to induce such effect. Single treatment (previous or late) with nicorandil (100mg/Kg, p.o.) also reduced neutrophils recruitment, although to a lesser extent when compared to the double treatment. Nicorandil reduced the concentrations of interleukin-1β, CXCL-1 and prostaglandin E2 in the pleural exudate. Concluding, we demonstrated the activity of nicorandil in a model of pleurisy induced by carrageenan. This activity was characterized by reduction of the neutrophil accumulation and inhibition of production of inflammatory mediators. The effects induced by nicorandil on the leukocytes recruitment and production of inflammatory mediators contribute to a better understanding of its clinical benefits and indicate that these benefits may be due to its vasodilating and anti-inflammatory activities.


[Patient safety incidents reported before and after the start of the COVID-19 pandemic in Primary Care in Tarragona].
To analyse and compare the epidemiology of patient safety incidents reported in Primary Health Care, before and after the start of the COVID-19 pandemic. Analytical descriptive study comparing reported incidents from March 1st 2019 to February 28th 2020, and from March 1st 2020 to February 28th 2021, notified through the TPSC Cloud™ platform accessible from the Intranet corporative in 25 Primary Health Care centres from Tarragona district, in Catalonia (Spain). Data obtained from voluntary notifications, through electronic, standardized and anonymized forms. Centre, professional, incident type, risk matrix, causal factors and contributing factors, and avoidability. Every notification was included in descriptive analysis, and another one specifically for adverse events, comparing both periods. 2231 incidents were reported. Comparing both periods, during the pandemic a reduction in the number of reported incidents was observed (only represented 20% of the total). However, the percentage of reported notifications from health care professionals and adverse events that required observation were increased. Causal factors related to attendance and diagnosis were incremented whereas the causal factors related to medication were decreased. In addition, an increase in contributing factors related to the professional was observed. Avoidability was high (>95%) in both periods. During the pandemic, fewer patient safety incidents have been reported, but proportionally more adverse events, most of which are preventable. The professional himself becomes the main contributing factor.


Cloning and sequencing of a cDNA encoding the canine HSP27 protein.
The nucleotide (nt) sequence encoding a 27-kDa heat-shock protein (HSP27) was determined from cDNAs cloned from a canine smooth muscle library. The primary structure deduced from the nt sequence reveals a 209-amino-acid protein having 86-89% identity with human, mouse, rat and hamster small HSP. Similar to human HSP27, the canine protein contains three Ser residues that are potential MAPKAP kinase II substrates.


Biochemical and in vivo voltammetric evidence for differences in striatal dopamine levels in inbred strains of mice.
High performance liquid chromatography with electrochemical detection and differential pulse voltammetry were used to provide a direct measurement of tissue content of dopamine and its metabolites and extracellular dopamine levels, respectively, in the striata of BALB/c and CBA inbred strains of mice. We found that levels of striatal dopamine and its metabolite, dihydroxyphenylacetic acid, were significantly higher in the CBA strain than in the BALB/c strain, whereas levels of homovanillic acid were not significantly different between the strains. Levels of the dopamine metabolite 3-methoxytyramine, on the other hand, were higher in the BALB/c mice. Dopamine turnover rates were significantly higher in the CBA strain when the homovanillic acid/dopamine ratio was used as an index of dopamine activity. Voltammetric recording showed that the local infusion of K+ in pargyline-treated mice resulted in the immediate appearance of a peak at +85 mV, which has been shown to correspond to extracellular dopamine in the rat. The mean height of this peak detected in vivo following K+ stimulation corresponds to in vitro dopamine concentrations of 25 +/- 8 microM for BALB/c mice and 7 +/- 2 microM for CBA mice. K(+)-stimulated dopamine release in the BALB/c mice could be evoked every 10-15 min with similar magnitude. In contrast, very little dopamine release in CBA mice could be evoked after the first stimulation. Since striatal dopamine levels are higher in CBA mice, these data suggest that (a) BALB/c strain may have more dopamine in the readily releasable pool, whereas the CBA mice have a larger storage pool of dopamine, and/or (b) that dopamine uptake in the CBA mice is much more avid than in BALB/c.


IL-36γ Induced by the TLR3-SLUG-VDR Axis Promotes Wound Healing via REG3A.
IL-36 family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to promote wound healing remains unknown. Here we showed that skin injury increased the expression of IL-36γ to promote wound healing. Mechanistically, the expression of IL-36γ was induced by RNAs from damaged cells via the activation of toll-like receptor 3 (TLR3) and TIR-domain-containing adapter-inducing IFN-β (TRIF) followed by the induction of a zinc finger protein SLUG to abrogate the inhibitory effect of vitamin D receptor (VDR) on the promoter of IL-36γ gene. IL-36γ acted back on keratinocytes to induce REG3A, which regulated keratinocyte proliferation and differentiation, thus promoting wound re-epithelialization. These observations show that skin injury increases IL-36γ via the activation of TLR3-SLUG-VDR axis and that IL-36γ induces REG3A to promote wound healing. These findings also provide insights into pathways contributing to wound repair.


Autoantibodies in the sera of patients with rheumatic heart disease: characterization of myocardial antigens by two-dimensional immunoblotting and N-terminal sequence analysis.
The concept of antigenic mimicry in autoimmune diseases such as rheumatic fever has been under investigation for decades and the range of cross-reactive tissue antigens for streptococcal-induced antibodies identified in rheumatic heart disease is still expanding. To identify heart tissue-reactive antigens which may be implicated in the secondary immunopathogenesis of rheumatic fever, sera from 56 patients with acute rheumatic heart disease were probed in two-dimensional Western blots for reactivity against heart tissue antigens. After two-dimensional immunoblot analysis, proteins were submitted to N-terminal amino acid sequence analysis. This analysis identified creatine kinase, two mitochondrial proteins and, at a low level, various stress proteins as cross-reactive myocardial antigens. Therefore, in addition to myosin, creatine kinase may represent another major antigen for autoreactive antibodies in rheumatic heart disease. Mitochondrial proteins have been implicated in the pathogenesis of inflammatory heart disease for some years, and in this study we have identified two mitochondrial proteins as relevant antigens in rheumatic heart disease.


Substrate specificity in plasmalogen biosynthesis. Desaturation of 1-O-hexadecyloxyethyl-2-acylglycero-3-phosphoethanolamine in developing rat brain.
1-O-[1'-14C]Hexadecyloxyethyl rac-glycerol was administered to 18-day-old rats by intracerebral injection, and incorporation of radioactivity into the brain lipids was determined after 6, 24 and 48 h. Some of the substrate was catabolized by oxidative cleavage of either of the two ether bonds. Cleavage in the hexadecyloxyethyl moiety yielded labeled palmitic acid, whereas oxidative cleaveage of the glycol glycerol ether bond produced O-hexadecyl glycolic acid. The substrate was also incorporated as such into both ethanolamine and choline phospholipids. Evidence is presented for the desaturation by rat brain of 1-O-hexadecyloxyethyl-2-acyl-sn-glycero-3-phosphoethanolamine to the plasmalogen analogue, while the corresponding choline phospholipid was not desaturated.


An update on sexual function and dysfunction in women.
Sexual function of women can be affected by many factors resulting in female sexual dysfunction (FSD). Sexual dysfunction is a common problem among women of all ages and has negative effects not only on their quality of lives but also on the sexual function and quality of life of their partners. It can also affect mental health of the entire family and society. Regarding the multidimensional nature of female sexual dysfunction and considering its consequences, this condition needs to be recognised in its early stages in order to prevent future consequences and impacts. This article discusses biopsychosocial aspect of female sexual function, classifications and risk factors of female sexual dysfunction and investigates current approaches to identify and treat this problem.


Infant abuse and neglect: lessons from the primate laboratory.
We review the several areas in which research on nonhuman primates contributes to our understanding of child abuse and neglect in human children. One special advantage of primate studies is that the experimental method can be utilized to examine the short- and long-term effects of relatively well-defined and circumscribed alterations in early experience and the manner in which they can affect later behavioral and physiological development. Four studies in M. nemestrina (pigtail) monkeys are described in which relatively short social separation experiences in infancy were associated with evidence of persistent changes in certain aspects of social behavioral functioning and immunological functioning, up to six years later, when the previously separated animals were in late adolescence or early adulthood. Such findings suggest that nonhuman primates may be used as animal model systems with considerable relevance to issues surrounding human child abuse and neglect.


Human papillomavirus vaccine policies among american Indian tribes in Washington State.
American Indians experience high rates of cervical cancer, which is preventable by vaccination against human papillomavirus (HPV). We sought information on funding, barriers, education, and policies regarding HPV vaccination from clinics that serve tribal members in the Pacific Northwest. We surveyed staff either by telephone or by using a mailed survey at 31 tribal and Indian Health Service clinics serving the 29 federally recognized American Indian tribes in Washington State. The survey included 11 items on policies and use of the HPV vaccine. Primary outcomes were funding options for HPV vaccine administration, barriers to vaccine delivery, potential gaps in education, and determination of tribal or clinic-specific policies. Thirty-one clinics provided information; 28 administered the vaccine. Vaccination was supported by federal, private, and tribal sources. Barriers were reported by 89% of clinics, most commonly patients' lack of knowledge, distrust of the medical system, and lack of funding. Patient and provider information was widely available. Thirteen clinics had either tribal or internal clinic vaccination policies, or both. HPV vaccine is available, but complex policies on administration could result in tribal differences in vaccination rates.