Nitrofurantoin damages DNA of human cells.
Nitrofurantoin causes damage to DNA of cultured diploid human fibroblasts. As a consequence DNA synthesis is blocked. The damage is removed by the normal enzymatic DNA repair system. Xeroderma pigmentosum fibroblasts which are defective in the excision endonuclease fail to repair nitrofurantoin-caused lesions.


Median nerve evoked potential changes in an acute carpal tunnel syndrome model in Macaca mulatta.
We devised an acute, carpal tunnel syndrome (CTS) model in rhesus monkey, Macaca mulatta. This model was used to observe the relationship between increases in compartmental pressure and nerve function as reflected in the electrophysiologically generated, averaged evoked potential recorded from the skin superficial to the median nerve at the elbow. Two waves, an A beta and A delta were monitored. Increased carpal tunnel pressure produced a decrease in the A beta wave amplitude which was occasionally preceded by a slight elevation, but which eventually resulted in A beta wave abolition with pressures greater than or equal to 31 mm Hg. The A delta wave showed an initial increase in amplitude followed by a decline and abolition. Recovery rate from increased pressure for the A beta wave was directly proportional to the rate of abolition of that wave. The implications of these data are discussed in the context of CTS neuropathology and diagnosis.


Y-shaped ZnO Nanobelts Driven from Twinned Dislocations.
Y-shaped ZnO nanobelts are fabricated by a simple thermal evaporation method. Transmission Electron Microscopy (TEM) investigation shows that these ZnO nanobelts are crystals with twinned planes {11-21}. Convergent Beam Electron Diffraction studies show that the two sides of twinned nanobelts are O-terminated towards the twinned boundary and Zn-terminated outwards. The two branches of twinned ZnO nanobelts grow along [11-26] from the trunk and then turn to the polarization direction [0001]. The featured Y-shape morphology and TEM characterizations indicate that the growth of these novel nanostructures is driven by an unusual twinned dislocation growth mechanism.


PPAR-delta promotes survival of breast cancer cells in harsh metabolic conditions.
Expression of the nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) in breast cancer cells is negatively associated with patient survival, but the underlying mechanisms are not clear. High PPARδ protein levels in rat breast adenocarcinomas were found to be associated with increased growth in soft agar and mice. Transgenic expression of PPARδ increased the ability of human breast cancer cell lines to migrate in vitro and form lung metastases in mice. PPARδ also conferred the ability to grow in exhausted tissue culture media and survive in low-glucose and other endoplasmic reticulum stress conditions such as hypoxia. Upregulation of PPARδ by glucocorticoids or synthetic agonists also protected human breast cancer cells from low glucose. Survival in low glucose was related to increased antioxidant defenses mediated in part by catalase and also to late AKT phosphorylation, which is associated with the prolonged glucose-deprivation response. Synthetic antagonists reversed the survival benefits conferred by PPARδ in vitro. These findings suggest that PPARδ conditions breast cancer cells to survive in harsh microenvironmental conditions by reducing oxidative stress and enhancing survival signaling responses. Drugs that target PPARδ may have a role in the treatment of breast cancer.


In-silico identification of fingerprint of pyrazolyl sulfonamide responsible for inhibition of N-myristoyltransferase using Monte Carlo method with index of ideality of correlation.
Human African trypanosomiasis (HAT) or sleeping sickness like infections remain a serious health concern around the globe due to unavailability of safe and potential drugs for their treatment. Moreover, developing safe, potential and highly specific target based treatments is still a challenge for present drug discovery programs. A series of pyrazole based sulfonamides are identified as an inhibitor of Trypanosoma brucei N-myristoyltransferase (TbNMT). In the present manuscript, we have developed robust and reliable QSAR models by using the balance of correlation method in CORAL software. The chemical structures are represented by simplified molecular input line entry system (SMILES). The significance of the index of ideality correlation (IIC) with applicability domain (AD) is also studied at depth. The models developed by considering the index of ideality of correlation (IIC) were found to statistically more significant and robust. One QSAR model with best Rcalibration2 = 0.8638 for split 2 was considered as the leading model. A greater value of cRp2i.e. 0.5 for all models in Y-randomization test showed the robustness of developed models. The outliers and promoters of increase and decrease of endpoint were also extracted independently from the leading models. The mechanistic interpretation of developed models explains the role of different structural attributes in predicting the pIC50 of pyrazole sulfonamides extracted from the crystal structure of Leishmania major N-myristoyltransferase (NMT) along with co-crystallized myristoyl-CoA and ligands NMT106, NMT157, NMT187 and NMT236 (PDB ID: 4A2Z, 4A30, 4A32, 2WSA). Communicated by Ramaswamy H. Sarma.


Platelet-derived growth factor-BB: a survival factor for the retinal microvasculature during periods of metabolic compromise.
The aim of this study was to test the hypothesis that platelet-derived growth factor (PDGF) reduces ischemia-induced damage to cells in the retinal microvasculature. As a model of ischemia, pericyte-containing microvessels freshly isolated from the adult rat retina were exposed to the inhibitors of ATP synthesis, iodoacetate and antimycin A. Cell viability was assayed by trypan blue exclusion. PDGF-BB significantly reduced cell death induced by chemical ischemia. The half-maximally effective concentration was approximately 15 pM. In contrast to PDGF-BB, which is the specific ligand for PDGF-beta receptors, ischemic death was not reduced by PDGF-AA, which does not activate the beta-receptors. The protective effect of PDGF-BB was blocked by tolbutamide, which is an inhibitor of ATP-sensitive potassium (K(ATP)) channels and mimicked by the K(ATP) channel opener, pinacidil. Nifedipine, which blocks voltage-gated calcium channels (VGCC's), also mimicked the protective effect of PDGF-BB. Consistent with PDGF-BB and nifedipine preventing cell death via a common mechanism, i.e., reducing VGCC activity, the maximal effects of this growth factor and the calcium channel blocker were not additive. Our results indicate that PDGF-BB significantly reduces the vulnerability of retinal microvessels to damage caused by profound ischemia. During episodes of metabolic compromise, it appears likely that the opening of K(ATP) channels via activation of PDGF-beta receptors initiates an adaptive mechanism to enhance the survival of the retinal microvasculature.


Rhinosporidiosis in bovines of Kanyakumari district, Tamil Nadu, India.
A survey on rhinosporidiosis in animals was conducted in Kanyakumari (K.K.) district of Tamil Nadu, India. Among 103 animals (40 bullocks, 45 cows, 15 heifers, 2 bulls and a buffalo), 19 (9 bullocks, 8 cows, 1 heifer and a she-buffalo) were found to be infected with Rhinosporidium seeberi. The study revealed the endemic nature of the disease in bovines of K.K. district. Agastheeswaram taluk contributed 52.6 per cent of positive cases followed by Kalkulam (26.2 per cent). The disease was also found in exotic cattle (1 Holstein Friesien (HF) cow, 1 Swiss Brown cow and 1 HF heifer). The rest 16 were indigenous non-descript cattle. There was no sex variance as the cases were evenly distributed between both sexes. One of the infected animals was a she-buffalo. A case of recurrence of growth was observed in a bullock. Another bullock had concurrent infection of both rhinosporidiosis and nasal schistosomiasis. All the animals were adults and aged except the heifer. All were nose-roped. Cows were stall fed but bathed in ponds.


Comparative analysis of isolated aortic valve replacement with fascia lata and homograft valves.
Thirty-eight consecutive patients who underwent isolated replacement of the aortic valve with fascia lata in 1970 were compared with a similar series of patients undergoing homograft replacement of the aortic valve. These series were well matched in number, age sex of patients, symptomatology, valvular disease, electrocardiographic and roentegenographic changes, and preoperative cardiac catheterization data. The mean follow-up time was 73 months in the fascia lata series and 69.1 months in the homograft series, and all the post-operative survivors were reviewed. The early and long-term results were similar of the two series, and there was no statistical difference in the operative and late mortality, the incidence of early and late diastolic murmurs, valve failure necessitating valve replacement, infective endocarditis, thromboembolism, over-all survival, and survival with an intact valve. It is concluded that the long-term results of valve replacement using these two tissues, in the aortic position, are similar and there is little to choose between the two types of valves. If fascia lata, as we believe, is no longer acceptable as a satisafactory valve substitute, then homograft valves are not acceptable either.


[Ischemic stroke in the young adult].
Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke.


Surgical outcome of patients with lung cancer involving the left atrium.
Pulmonary and left atrial resection is not yet an established treatment for patients with primary lung cancer involving the left atrium. We investigated the clinical course of patients with primary lung cancer involving the left atrium who were treated with pulmonary resection and partial atrial resection. From January 1996 to December 2013, 51 patients underwent extended resection for lung cancer that invaded the surrounding organs. Of these, we focused on 12 patients who underwent surgical treatment for lung cancer involving the left atrium. The clinical course of each of these patients was investigated retrospectively. The most common histological subtype was squamous cell carcinoma. Pneumonectomy was performed in nine patients, and right middle and lower lobectomy was performed in three patients. Complete resection was performed in 11 patients (92 %). Postoperative complications were observed in four patients (33 %)-prolonged air leakage in two patients, broncho-pleural fistula in one patient, and empyema in one patient. There were no surgical deaths. This study involved seven patients with pathological N0-1 disease and five patients with pathological N2 disease. The postoperative 5-year survival rate was 46 % in all patients. The 5-year survival rates in patients with pathological N0-1 disease and N2 disease were 67 and 20 %, respectively. Because treatment-related death was not observed and outcome was fair in patients with N0-1 disease, surgical resection for primary lung cancer involving the left atrium may be acceptable in selected patients. Further investigations are required to improve the outcome of surgical treatment for patients with primary lung cancer involving the left atrium.


A laboratory-based study for first documented case of urinary myiasis caused by larvae of Megaselia scalaris (Diptera: Phoridae) in Saudi Arabia.
Megaselia scalaris (Diptera: Phoridae) is one of the medically important insects. Maggots from a urine sample of a 5-year-old Saudi girl were examined microscopically for identification. These maggots were cultured to become adult flies. Larvae and adults were identified using standard keys. Protozoan flagellates were obtained from the gut of the larvae. This is the first report of M. scalaris as a causative agent of urinary human myiasis in Saudi Arabia.


Molecular data reveal a new species of Seuratascaris Sprent, 1985 (Nematoda: Ascaridoidea) from Quasipaa exilispinosa (Liu & Hu) (Amphibia: Anura).
The genus Seuratascaris Sprent, 1985 is a group of obligate nematode parasites of amphibians. In the present study, a new species of Seuratascaris, S. physalis sp. n. was described using light and scanning electron microscopy based on specimens collected from Quasipaa exilispinosa (Liu & Hu) (Amphibia: Anura) in China. The new species differs from S. numidica (Seurat, 1917) by the cuticle of the cervical region distinctly inflated to form a cephalic vesicle-like structure and the absence of single medio-ventral precloacal papilla. The molecular characterization of the nuclear large ribosomal DNA (28S) and internal transcribed spacer (ITS) and the mitochondrial cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 2 (cox2) and 12S small subunit ribosomal RNA gene of S. physalis sp. n., together with the 28S, cox2 and 12S of S. numidica are provided for the first time. Molecular analysis revealed the presence of high level of interspecific genetic variation between the two species in the ITS (5.50%), cox1 (13.3%), cox2 (10.6%) and 12S regions (10.5%), which strongly supported that S. physalis sp. n. represented a different species from S. numidica. Angusticaecum ranae Wang, Zhao & Chen, 1978 reported from the frog Quasipaa spinosa (David) (Anura: Dicroglossidae) in China was transferred into the genus Seuratascaris as S. ranae (Wang, Zhao & Chen, 1978) comb. n. based on the morphology of lips and the presence of very short and robust spicules without alae and small numbers of precloacal papillae. The present study provided useful genetic data for molecular identification of species of Seuratascaris and provides the foundation for being able to determine if S. numidica represents a species complex of some sibling species or a single species.


Indirect predictive type-2 fuzzy neural network controller for a class of nonlinear input - delay systems.
In this paper a new indirect type-2 fuzzy neural network predictive (T2FNNP) controller has been proposed for a class of nonlinear systems with input-delay in presence of unknown disturbance and uncertainties. In this method, the predictor has been utilized to estimate the future state variables of the controlled system to compensate for the time-varying delay. The T2FNN is used to estimate some unknown nonlinear functions to construct the controller. By introducing a new adaptive compensator for the predictor and controller, the effects of the external disturbance, estimation errors of the unknown nonlinear functions, and future sate estimation errors have been eliminated. In the proposed method, using an appropriate Lyapunov function, the stability analysis as well as the adaptation laws is carried out for the T2FNN parameters in a way that all the signals in the closed-loop system remain bounded and the tracking error converges to zero asymptotically. Moreover, compared to the related existence predictive controllers, as the number of T2FNN estimators are reduced, the computation time in the online applications decreases. In the proposed method, T2FNN is used due to its ability to effectively model uncertainties, which may exist in the rules and data measured by the sensors. The proposed T2FNNP controller is applied to a nonlinear inverted pendulum and single link robot manipulator systems with input time-varying delay and compared with a type-1 fuzzy sliding predictive (T1FSP) controller. Simulation results indicate the efficiency of the proposed T2FNNP controller.


A method to evaluate skill transfer and acquisition of obstetric gestures based on the curvatures analysis of the position and the orientation.
This paper focuses on the gesture analysis in order to compare two human gestures. The orientations and the positions of the gestures are both taken into account and the similarity rate between two gestures is calculated. In our case, the application is in obstetrics and the aim is to evaluate forceps blade placement. The method is based on the curvature analysis of the paths during the gesture. The 3-D position paths are expressed according to their cumulated chord length and the orientation paths in the quaternion unit space. These parameterizations lead to analyze data in space independently to time as requested by physicians. After filtering data in order to minimize sensor noises, the gestures are then compared by calculating the correlation between the position and the orientation curvatures of a novice gesture and an expert one. The results clearly show that novice skills in handling forceps increase in becoming smoother and closer to the reference placement. A childbirth simulator allows novices to acquire experience without any risks, however the training have to be completed with the extraction gesture evaluation and a compulsory training period in the delivery ward.


Primary Immune Thrombocytopenia: A Translational Research Model for Autoimmune Diseases.
Primary immune thrombocytopenia (ITP), formally known as idiopathic thrombocytopenic purpura, is a multifactorial autoimmune disease that is both idiopathic (cause unknown) and rare [...].


Osteoarthritis, a disease bridging development and regeneration.
The osteoarthritic diseases are common disorders characterized by progressive destruction of the articular cartilage in the joints, and associated with remodeling of the subchondral bone, synovitis and the formation of bone outgrowths at the joint margins, osteophytes. From the clinical perspective, osteoarthritis leads to joint pain and loss of function. Osteoarthritis is the leading cause of progressive disability. New data from genetic, translational and basic research have demonstrated that pathways with essential roles in joint and bone development also contribute to the postnatal homeostasis of the articular cartilage and are involved in osteoarthritis, making these potential therapeutic targets. Other systems of interest are the tissue-destructive enzymes that break down the extracellular matrix of the cartilage as well as mediators of inflammation that contribute to synovitis. However, the perspective of a durable treatment over years to decades highlights the need for a personalized medicine approach encompassing a global view on the disease and its management, thereby including nonpharmaceutical approaches such as physiotherapy and advanced surgical methods. Integration of novel strategies based on their efficacy and safety with the identification of individuals at risk and optimal individual rehabilitation management remains a major challenge for the medical community in particular, as the incidence of osteoarthritis is likely to further increase with the overall aging of the population.


Cardiac arrest in type II Kounis syndrome after oral intake of amoxicilline.
Kounis syndrome (KS) is defined as the occurrence of an acute coronary syndrome related to allergic or hypersensitivity reaction. KS is currently classified into three variants, based on coronary arteries status. This syndrome is often neglected or misdiagnosed in clinical practice. We described a type II KS case. This acute coronary syndrome (ACS) began with cardiac arrest (an uncommon clinical expression for KS) immediately after oral intake of amoxicilline. Coronary angiography revealed coronary arteries stenoses which were considered unsuitable for revascularization. Optimization of medical therapies was the goal of the management for this patient. Follow-up visits revealed normal echocardiographic findings and no malignant arrhythmias at ECG Holter monitoring. KS can be a rare case for ACS, sometimes occurring with sudden cardiac arrest. Physicians should pay attention to the history of the patients in order to identify the correct cause of ACSs.


Regional uveal response to increased nutritional needs in the retinal zone of the developing eye demonstrated in an eye with retinoblastoma.
The outer layers of the normal retina depend on indirect nutrition originating in the choriocapillaris and supplied to the retina by way of the pigment epithelium. An eye with exophytic retinoblastoma is used to demonstrate increased vascularity and tissue substance in the adjacent choroid believed to be indirectly induced by a regional increase in nutritional requirements in the retinal zone of a developing eye.


Analysis of 133 patients with severe blunt liver injury.
To investigate the treatment and causes of death about severe blunt liver injury. The data of 133 patients with severe blunt liver injury (Grade III to Grade V) were analyzed retrospectively. All the patients except 2 underwent operations. Different types of surgical procedures were adopted according to the severity of liver injury. Operations were the major method to treat hepatic injury. The total mortality rate was 21.0% in this study. The mortality rates of Grade III, Grade IV and Grade V of liver injuries were 11.3%, 24.4% and 69.2%, respectively. Packing treatment plays an important role in the treatment of hepatic injury. The mortality rate is related closely to the severity of hepatic injury, multiple trauma, shock and disturbance of blood coagulation.


The case for improved transdiagnostic detection of first-episode psychosis: Electronic health record cohort study.
Improving outcomes of a First Episode of Psychosis (FEP) relies on the ability to detect most individuals with emerging psychosis and treat them in specialised Early Intervention (EI) services. Efficacy of current detection strategies is undetermined. RECORD-compliant clinical, 6-year, retrospective, transdiagnostic, lifespan-inclusive, Electronic Health Record (EHR) cohort study, representing real-world secondary mental healthcare in South London and Maudsley (SLaM) NHS. All individuals accessing SLaM in the period 2007-2017 and receiving any ICD-10 diagnosis other than persistent psychosis were included. Descriptive statistics, Kaplan-Meier curves, logistic regression, epidemiological incidence of psychosis in the general population were used to address pathways to care and detection power of EI services for FEP. A total of 106,706 individuals underwent the 6-year follow-up: they were mostly single (72.57%) males (50.51%) of white ethnicity (60.01%), aged on average 32.96 years, with an average Health Of the Nation Outcome Scale score of 11.12 and mostly affected with F40-48 Neurotic/stress-related/somatoform disorders (27.46%). Their transdiagnostic risk of developing a FEP cumulated to 0.072 (95%CI 0.067-0.077) at 6 years. Those individuals who developed a FEP (n = 1841) entered healthcare mostly (79.02%) through inpatient mental health services (29.76%), community mental health services (29.54%) or accident and emergency departments (19.50%); at the time of FEP onset, most of them (46.43%) were under the acute care pathway. Individuals contacting accident and emergency departments had an increased risk of FEP (OR 2.301, 95%CI 2.095-2.534, P < 0.001). The proportion of SLaM FEP cases that were eligible and under the care of EI services was 0.456 at any time. The epidemiological proportion of FEP cases in the sociodemographically-matched general population that was detected by EI service was 0.373. More than half of individuals who develop a FEP remain undetected by current pathways to care and EI services. Improving detection strategies should become a mainstream area in the future generation of early psychosis research.


Human cutaneous topography a new photographic technique: observations on normal skin.
We describe herein a convenient and inexpensive technique for photographic examination of the surface of the skin. With this method, the fine lines of the skin appear as furrows or folds. The furrows demarcate units of epidermal structure which we have designated polyangular units. These, in turn, are arranged in a mosaic pattern. This technique was used to define the topography of normal young adults. Surface features fall into four major patterns: 1) dermatoglyphic, 2) hair bearing, 3) frictional, and 4) flexural.


Thiazole- and selenazole-comprising high-affinity inhibitors possess bright microsecond-scale photoluminescence in complex with protein kinase CK2.
A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB) revealed remarkable room temperature phosphorescence when bound to the ATP pocket of the protein kinase CK2. Conjugation of these fragments with a mimic of CK2 substrate peptide resulted in bisubstrate inhibitors with increased affinity towards the kinase. Attachment of the fluorescent acceptor dye 5-TAMRA to the conjugates led to significant enhancement of intensity of long-lifetime (microsecond-scale) photoluminescence of both sulfur- and selenium-containing compounds. The developed photoluminescent probes make possible selective determination of the concentration of CK2 in cell lysates and characterization of CK2 inhibitors by means of time-gated measurement of photoluminescence.


Fractures of the metacarpals: treatment by A. O. screw and plate fixation.
Twenty-two patients with 26 fractured metacarpals were treated by internal fixation using A. O. mini-fragment screws and plates. This form of internal fixation was reserved for metacarpal fractures which were multiple, unstable, displaced or rotated. Nine patients had open fractures, two had divided extensor tendons and four had multiple fractures. Fractures consistently united without infection or deformity. The mean duration of postoperative immobilization was seven days and mean time off work was six weeks. All but one patient did manual work. No patients had persistent symptoms which caused difficulty with work or sport. Fourteen patients regained full movement. Four had total active movement of 220 degrees or more in the involved ray and 6 patients had total active movement of between 180 and 220 degrees. Restricted movement was present in patients with open fractures and divided extensor tendons or intra-articular fractures of the metacarpal head. Uniformly satisfactory results were found after mini-screw and plate fixation of metacarpal fractures.


The predictive value of coexisting BRAFV600E and TERT promoter mutations on poor outcomes and high tumour aggressiveness in papillary thyroid carcinoma: A systematic review and meta-analysis.
BRAFV600E mutation is highly prevalent in patients with papillary thyroid carcinoma (PTC), and TERT promoter (TERTp) mutation is strongly associated with cancer-related mortality. However, predictive power of the two mutations remains inconclusive. We aimed to verify the prognostic effects of both mutations to assess the value of mutation detection for risk stratification in terms of PTC prognosis and tumour invasion, to guide PTC diagnosis and treatment. We conducted a literature search in the MEDLINE (PubMed), EMBASE, Web of Science and CENTRAL (Cochrane library) databases, from inception to February 2020. Basic characteristics, prognoses and clinicopathological features were collected from the included studies for further analysis. Twelve studies involving 4184 PTC patients were enrolled in our analysis. In total, 2412 (57.6%) of the patients carried either BRAFV600E or TERTp mutation, and 290 (6.9%) patients had both mutations. TERTp mutation was more common in patients with BRAFV600E mutation (RR = 1.75 [95% CI 1.44-2.13]). Patients with both mutations had a worse prognosis compared with those with a single mutation (vs BRAFV600E only: RR = 5.34 [4.20-6.78] vs TERTp only: RR = 2.12 [1.41-3.19]). TERTp mutation alone independently increased the risk of a poor prognosis (RR = 2.90 [1.93-4.35]) in terms of mortality (RR = 15.09 [7.75-29.37]), disease persistence (RR = 4.00 [2.03-7.90]), recurrence (RR = 4.34 [4.20-6.78]), lymph node metastasis (RR = 1.57 [1.24-1.99]) and distant metastasis (RR = 2.94 [1.13-7.65]). We found that PTC patients with BRAFV600E mutation were more likely to have TERTp mutation. TERTp mutation was an independent predictive factor for poor prognosis of PTC patients, but the predictive value of BRAFV600E mutation remains inconclusive. Patients with both mutations have remarkably higher risks of adverse outcomes compared with those with a single mutation. PTC patients could benefit from mutation detection for aiding risk stratification (BRAF + TERT+ > BRAF - TERT+ > BRAF + TERT-).


Comments on the Discussion Forum: Oromucosal immunomodulation as clinical spectrum mitigating factor in SARS-CoV-2 infection.
The mammalian lactoperoxidase system, consisting of lactoperoxidase and the H2 O2 -producing enzyme duox, is our first line of defence against airborne microbes. This system catalyses the production of hypoiodite and hypoiodous acid in the presence of sufficient iodine. These products are highly efficient at destroying the H1N1 virus and the respiratory syncytial virus (RSV). Japan has not been affected as much as other nations during the COVID-19 pandemic (death rate about 10% of the United States), and we think this is due to a diet high in iodine. With this in mind, we suggest four actions to prevent SARS-CoV-2 infections. First, health professionals should study the preventative effect of increasing iodine in the diets of the aged, institutionalized, diabetics andsmokers. Second, the recommended daily intake (RDI) for iodine should be significantly increased, to at least double, the current RDI. Governments should encourage the use and distribution of cheap iodized salts, kelp and seaweed. Third, more research should be done around the physiology and the protective effects of the lactoperoxidase system. Finally, the degradation products of the SARS-CoV-2 viral particle by hypoiodite and hypoiodous acid should be characterized; portions of the damaged particle are likely to elicit stronger immunity and better vaccines.


Barriers and facilitators to pressure injury prevention in hospitals: A mixed methods systematic review.
To systematically synthesize research evidence on barriers and facilitators to pressure injury prevention in hospital settings. A systematic literature review of quantitative, qualitative, and mixed methods research was undertaken using PubMed, MEDLINE, Embase, CINAHL, and Cochrane Library. Studies that reported barriers or/and facilitators to pressure injury prevention in the acute care settings and published in English from 2008 to 2022 were included. Studies were excluded if they were conducted in residential care facilities and nursing homes, or other long-term community care settings. Two authors independently screened articles against the inclusion and exclusion criteria. Quality appraisal was conducted by two authors by using the Mixed Methods Appraisal Tool. Reported results were mapped to the Theoretical Domains Framework to identify the barriers and facilitators to pressure injury prevention. A total of 78 studies were included. There were 65 quantitative studies, 11 qualitative studies, and two mix-methods studies. The most salient Theoretical Domains Framework domains identified in this review were "Knowledge", "Skills", "Environmental Context and Resources", "Optimism", "Social/Professional Role and Identity", and "Social influences". The barriers and facilitators to pressure injury prevention in hospital settings identified in this systematic review were diverse, and included issues at both individual and organizational level. Healthcare organizations can address the barriers and facilitators from the influential Theoretical Domains Framework domains. Future research is required to investigate the effectiveness of behaviour change interventions that specifically target these barriers and facilitators to pressure injury prevention.


Multimodality preoperative treatment for advanced cancer of the head and neck.
Neoadjuvant induction chemotherapy with cisplatin, methotrexate, and bleomycin appears to improve the results of treatment of advanced stage IV head and neck cancer, compared with results in historical control subjects. Patients treated with induction chemotherapy and radiation therapy had a 29 percent overall survival rate at 3 years, which represents approximately a twofold improvement in the survival rate. Patients who were treated with chemotherapy and radiation therapy followed by surgery had more than a threefold increase in the survival rate (49 percent at 3 years), compared with historical data from our institution and elsewhere for such patients [9-11]. Distant metastases developed in 25 percent of the patients, and it thus appears that long-term, effective consolidation and maintenance chemotherapy [12,13] need to be developed for patients who receive combination therapy before surgery for head and neck cancer.


In vivo involvement of cytochrome P450 4A family in the oxidative metabolism of the lipid peroxidation product trans-4-hydroxy-2-nonenal, using PPARalpha-deficient mice.
Trans-4-hydroxy-2-nonenal (HNE) is a potent cytotoxic and genotoxic compound originating from the peroxidation of n-6 polyunsaturated fatty acids. Its metabolism has been previously studied in the rat (Alary et al. 1995. Chem. Res. Toxicol., 8: 35-39). In addition to major urinary mercapturic derivatives, some polar urinary metabolites were isolated and could correspond to hydroxylated compounds. 4-Hydroxynonenoic acid (HNA), resulting from the oxidation of the HNE carbonyl group, is a medium chain fatty acid and its omega-hydroxylation might be hypothesized. Therefore, the involvement of the CYP 4A family isoenzymes in the metabolism of [3H]HNE has been investigated in vivo using inducer treatments (fibrates) in wild-type or in peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice. In wild-type mice, but not in PPARalpha (-/-) mice, fibrate treatments resulted in an increase of two urinary metabolites characterized, after HPLC purifications and mass spectrometry analyses, as the omega-hydroxylated metabolite of HNA, i.e., 4,9-dihydroxy-2-nonenoic acid, and its oxidized form, 4-hydroxy-2-nonene-1,9-dicarboxylic acid. The formation of the latter is correlated accurately to laurate hydroxylase activity studied concurrently in microsomes prepared from the liver of these animals. Basal levels of these two metabolites were measured in urine of normal and PPARalpha-deficient mice. These results are in accord with an implication of the P450 4A family in the extended oxidative metabolism of 4-HNE.


Outcome of Application of Cryopreserved Amniotic Membrane Grafts in the Treatment of Chronic Nonhealing Wounds of Different Origins in Polymorbid Patients: A Prospective Multicenter Study.
To compare the therapeutic efficacy of cryopreserved amniotic membrane (AM) grafts and standard of care (SOC) in treating nonhealing wounds (NHW) through a prospective multicenter clinical trial, 42 patients (76% polymorbid) with 54 nonhealing wounds of various etiologies (mainly venous) and an average baseline size of 20 cm2 were included. All patients were treated for at least 6 weeks in the center before they were involved in the study. In the SOC group, 29 patients (36 wounds) were treated. If the wound healed less than 20% of the baseline size after 6 weeks, the patient was transferred to the AM group (35 patients, 43 wounds). Weekly visits included an assessment of the patient's condition, photo documentation, wound debridement, and dressing. Quality of life and the pain degree were subjectively reported by patients. After SOC, 7 wounds were healed completely, 1 defect partially, and 28 defects remained unhealed. AM application led to the complete closure of 24 wounds, partial healing occurred in 10, and 9 remained unhealed. The degree of pain and the quality of life improved significantly in all patients after AM application. This study demonstrates the effectiveness of cryopreserved AM grafts in the healing of NHW of polymorbid patients and associated pain reduction.


A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis.
Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75-0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63-1.27), 0.74 (95% CI: 0.62-0.89) and 0.86 (95% CI: 0.79-0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.


Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer.
Molecular biology achieves control over complex reaction networks by means of molecular systems that translate a chemical input (such as ligand binding) into an orthogonal chemical output (such as acylation or phosphorylation). We present an artificial molecular translation device that converts a chemical input - the presence of chloride ions - into an unrelated chemical output: modulation of the reactivity of an imidazole moiety, both as a Brønsted base and as a nucleophile. The modulation of reactivity operates through the allosteric remote control of imidazole tautomer states. The reversible coordination of chloride to a urea binding site triggers a cascade of conformational changes in a chain of ethylene-bridged hydrogen-bonded ureas, switching the chain's global polarity, that in turn modulates the tautomeric equilibrium of a distal imidazole, and hence its reactivity. Switching reactivities of active sites by dynamically controlling their tautomer states is an untapped strategy for building functional molecular devices with allosteric enzyme-like properties.


Accumulation of components of basal laminae: association with the failure of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice.
Aganglionosis occurs in the terminal colon of the ls/ls mouse because an intrinsic defect of the presumptive aganglionic tissue prevents the entry and colonization of this portion of the bowel by migrating neural crest cells. The current study was undertaken to determine if abnormalities of the extracellular matrix could be identified in this segment that might account for migratory failure. Since basal laminae of the muscularis mucosa are overproduced in the aganglionic segment of adult ls/ls mice, we examined components of basal laminae in fetal gut from Day E 11 to Day E 16 of gestation. This period spans the time of enteric ganglion formation. Laminin and collagen type IV were studied by immunocytochemistry and proteoglycans by staining glycosaminoglycans with Alcian blue. Abnormalities of each of these components occur during development of the presumptive aganglionic bowel in the ls/ls mouse and could be detected as early as Day E 11. These defects consist mainly of an overabundance of these materials, both in defined basal laminae and throughout the extracellular space of the mesenchyme. Electron microscopic observations in the presumptive aganglionic ls/ls colon revealed a thickening of basal laminae and exceptionally wide intercellular spaces between smooth muscle myoblasts that contained an irregular fibrillar material, consisting of 4.5- to 6.0-nm filaments associated with 14- to 20-nm granules. Fibrillar and flocculant material was continuous with formed basal laminae, and was concentrated in the same areas found to have an overabundance of laminin immunoreactivity. These observations indicate that there is an accumulation of extracellular matrix material, including components of basal laminae, that (i) precedes the formation of enteric ganglia, (ii) is in the path through which enteric neural precursors from the crest would have to migrate, and (iii) is limited to the aganglionic and hypoganglionic ls/ls bowel. These data are consistent with the hypothesis that components of basal laminae contribute to the inability of crest cells to colonize the terminal bowel of ls/ls mice.


Prediction of lymph node and distant metastasis in patients with endometrial carcinoma: a new model based on demographics, biochemical factors, and tumor histology.
To develop a model that might predict the probability of lymph node and distant metastasis (stages IIIC-IV) in endometrial carcinoma. We studied 774 patients with endometrial carcinoma treated in a single institution. Demographic factors, biochemical factors and preoperative tumor characteristics, identified as potential risk factors for advanced carcinoma in unadjusted analyses, were used to create a logistic regression model with lymph node and distant metastasis as the dependent variable. Statistically significant odds ratios in the regression model were rounded to the nearest whole number. These rounded values were the estimated weights for each factor that were summed to generate a score that might predict the probability of stage IIIC-IV carcinoma. Biochemical factors and preoperative tumor characteristics predicted lymph node and distant metastasis in the regression model, whereas demographic factors were without effect. The score combining weighted risk factors was: (2 × leukocytosis)+(3 × thrombocytosis)+(7 × elevated CA125)+(4 × high-risk histology). The area under curve (AUC) for this total score was 0.823, with 71.6% sensitivity, 75.2% specificity, 25.9% positive predictive value, and 95.7% negative predictive value, using 6 as cut-point. After excluding stage IV carcinomas from the dataset, the AUC was 0.813 for the total score in predicting nodal involvement (P=0.82 vs. total score in predicting stage IIIC-IV carcinomas in the complete dataset). Based on the high negative predictive value, this prediction model could be applied for identifying patients who may not benefit from lymphadenectomy for endometrial carcinoma staging.


Molecular cloning, expression, and immunolocalization of protein disulfide isomerase in excretory-secretory products from Clonorchis sinensis.
Protein disulfide isomerase (PDI) is an essential catalyst of the endoplasmic reticulum with folding and chaperone activities in different biological systems. Here, PDI of Clonorchis sinensis (CsPDI) was isolated from the cDNA library of adult C. sinensis. The open reading frame contains 1,317 bp encoding 438 amino acids and shares 53 %, 49 %, and 43 % identity with PDI from Bos taurus, Homo sapiens, and Schistosoma mansoni, respectively. Two catalytic thioredoxin motifs CxxC were found in this sequence, which were characteristic domains of thioredoxin superfamily. The CsPDI protein was expressed and purified from Escherichia coli BL21 (DE3). According to western blotting analysis, the recombinant CsPDI could be recognized by anti-CsPDI rat serum, anti-excretory/secretory products rat serum, and serum of rat infected with C. sinensis, respectively. Quantitative real-time polymerase chain reaction showed that transcription level of CsPDI in the metacercaria stage was six and four times higher than that in the adult worm and egg stage, respectively. Immunolocalization analysis showed CsPDI could be detected in the intestine, vitellarium, and intrauterine eggs of adult worm, as well as in the cyst wall and vitellarium of metacercaria. In addition, the strong fluorescence signal was observed both on the wall of bile duct and in the lumen of liver tissue of C. sinensis-infected cat. Those results demonstrated that CsPDI was a component of C. sinensis excretory-secretory products. The present study will enhance our understanding of biological functions of CsPDI and pave the way for further studies on host-parasite interaction during C. sinensis infection.


Orgons and biolons in theoretical biology: phenomenological analysis and quantum analogies.
In this paper we define two types of formal biological entities corresponding to biological levels of organization, the biolons and the orgons, the properties of which are phenomenologically analyzed and discussed. We examine then, in a rather speculative manner, how some characteristics of these entities may suggest analogies between properties of biological systems and some special features of quantum systems. These analogies are principally related to the specific roles played by these entities (relatively to matter-energy, for orgons, and to information, for biolons) in a biological system. They are funded on the formal equivalence between the temporal variations associated to the development of the orgons and the biolons, respectively, and the statistical distribution over the available energy levels of the two main types of quantum entities, the fermions and the bosons (the former being associated to the constitution of matter and the latter to the effects of interactions). This formal comparison leads us to put into correspondences the developmental duration in biological systems with the energetic structuration in quantum ones and the related characteristic times of the former with the temperature of the latter. We discuss briefly these correspondences.


Disruption of the glucagon receptor increases glucagon expression beyond α-cell hyperplasia in zebrafish.
The glucagon receptor (GCGR) is a potential target for diabetes therapy. Several emerging GCGR antagonism-based therapies are under preclinical and clinical development. However, GCGR antagonism, as well as genetically engineered GCGR deficiency in animal models, are accompanied by α-cell hyperplasia and hyperglucagonemia, which may limit the application of GCGR antagonism. To better understand the physiological changes in α cells following GCGR disruption, we performed single cell sequencing of α cells isolated from control and gcgr-/- (glucagon receptor deficient) zebrafish. Interestingly, beyond the α-cell hyperplasia, we also found that the expression of gcga, gcgb, pnoca, and several glucagon-regulatory transcription factors were dramatically increased in one cluster of gcgr-/- α cells. We further confirmed that glucagon mRNA was upregulated in gcgr-/- animals by in situ hybridization and that glucagon promoter activity was increased in gcgr-/-;Tg(gcga:GFP) reporter zebrafish. We also demonstrated that gcgr-/- α cells had increased glucagon protein levels and increased granules after GCGR disruption. Intriguingly, the increased mRNA and protein levels could be suppressed by treatment with high-level glucose or knockdown of the pnoca gene. In conclusion, these data demonstrated that GCGR deficiency not only induced α-cell hyperplasia but also increased glucagon expression in α cells, findings which provide more information about physiological changes in α-cells when the GCGR is disrupted.


Scandinavian SSAI clinical practice guideline on pre-hospital airway management.
The Scandinavian society of anaesthesiology and intensive care medicine task force on pre-hospital airway management was asked to formulate recommendations following standards for trustworthy clinical practice guidelines. The literature was systematically reviewed and the grading of recommendations assessment, development and evaluation (GRADE) system was applied to move from evidence to recommendations. We recommend that all emergency medical service (EMS) providers consider to: apply basic airway manoeuvres and airway adjuncts (good practice recommendation); turn unconscious non-trauma patients into the recovery position when advanced airway management is unavailable (good practice recommendation); turn unconscious trauma patients to the lateral trauma position while maintaining spinal alignment when advanced airway management is unavailable [strong recommendation, low quality of evidence (QoE)]. We suggest that intermediately trained providers use a supraglottic airway device (SAD) or basic airway manoeuvres on patients in cardiac arrest (weak recommendation, low QoE). We recommend that advanced trained providers consider using an SAD in selected indications or as a rescue device after failed endotracheal intubation (ETI) (good practice recommendation). We recommend that ETI should only be performed by advanced trained providers (strong recommendation, low QoE). We suggest that videolaryngoscopy is considered for ETI when direct laryngoscopy fails or is expected to be difficult (weak recommendation, low QoE). We suggest that advanced trained providers apply cricothyroidotomy in 'cannot intubate, cannot ventilate' situations (weak recommendation, low QoE). This guideline for pre-hospital airway management includes a combination of techniques applied in a stepwise fashion appropriate to patient clinical status and provider training.


The gut microbiome, diet, and links to cardiometabolic and chronic disorders.
Cardiometabolic diseases (CMDs) have been associated with changes in the composition of the gut microbiota, with links between the host environment and microbiota identified in preclinical models. High-throughput sequencing technology has facilitated in-depth studies of the gut microbiota, bacterial-derived metabolites, and their association with CMDs. Such strategies have shown that patients with CMDs frequently exhibit enrichment or depletion of certain bacterial groups in their resident microbiota compared to healthy individuals. Furthermore, the ability to transfer resident gut microbiota from mice or humans into germ-free mouse models, or between human patients, has enabled researchers to characterize the causative role of the gut microbiota in CMDs. These approaches have helped identify that dietary intake of choline, which is metabolized by the gut microbiota, is associated with cardiovascular outcomes in mice and humans. Trimethylamine N-oxide (TMAO) - a metabolite derived from the gut microbiota - is also associated with poor cardiovascular outcomes in patients with cardiovascular disease and is elevated in patients with chronic kidney disease (CKD). TMAO might represent a biomarker that links the environment and microbiota with CKD. This Review summarizes data suggesting a link between the gut microbiota and derived metabolites with food intake patterns, metabolic alterations, and chronic CMDs.


[Barbie goes PriMa: formative evaluation of a school-based program for the primary prevention of anorexia nervosa developed for girls up to the age of 12].
Recently, a newly developed German program for the prevention of anorexia nervosa in girls ("PriMa") was successfully tested for effectiveness in a controlled study with prepost-design in 1,006 girls from 42 Thuringian schools (Berger et al. 2007). In the present article the test of the program's effectiveness was completed by an evaluation of the program's conception and its process. Using questionnaires, protocols and phone interviews, single parts of the program (kick-off presentation, n = 400; teachers training, n = 34; lessons, n = 392) as well as single lessons (n = 87 girls and n = 14 teachers) were evaluated. All parts of the program were evaluated as being significantly positive (better than 2.5 on a six-point scale). The questionnaires used were reliable (Cronbach's alpha between .74 and .84). The survey of program users resulted in shorter research questionnaires, a more detailed teaching manual with more interactive exercises and smaller training groups (14 instead of 20 participants). The introduced work points out the need to complete the evaluation of program impact with verbal and written evaluations of direct and indirect program users. This is the only way to reveal information about the program's strengths and weaknesses to continuously adjust and improve single program parts.


MAPK signalling in rheumatoid joint destruction: can we unravel the puzzle?
Mitogen-activated protein kinases (MAPKs) have been associated with the pathogenesis of rheumatoid arthritis (RA), but the individual contributions of the three MAPK family members are incompletely understood. Although previous data have established a role for c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) in different animal models of arthritis, most recent data indicate that the stable activation of p38 MAPK and in part of ERK significantly contributes to destructive arthritis in mice transgenic for human tumour necrosis factor-alpha. These data highlight the complexity of MAPK signalling in arthritis and provide a basis for the design of novel strategies to treat human RA.


Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.
The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.


The corporatization of dermatopathology.
The corporatization of dermatopathology has long preceded that of dermatology and has been driven by federal legislation and economic influences. Although the Clinical Laboratory Improvement Amendments and the Stark Law limited physician-owned laboratories, loopholes via the Safe Harbor Exemptions outlined in the Anti-Kickback Statute allowed corporate laboratories to flourish through relationships built by health information technology donations. The rise of corporatization has had widespread effects on the fields of dermatopathology and dermatology, resulting in reduced numbers of dermatology-trained dermatopathologists and decreased caseloads in academic institutions, potentially compromising dermatology residency education. Although there have been efforts to counteract these effects, more global changes will be required to alter the direction of this subspecialty.


A varnish to prevent etching unrestored enamel.
The prognosis of acid-etched enamel was investigated in both laboratory and clinical experiments. Acid etching produced irregularities even on the prismless layer that covers prism enamel. The irregularities produced by etching are not remineralized in vivo but are filled with organic debris. Brushing reduced the depth of the irregularities but did not eliminate them. A protective varnish against acid etching was developed. The varnish also serves as a guide to facilitate removal of excess resin beyond the cavosurface margin.


TLP01, an mshA mutant of Vibrio cholerae O139 as vaccine candidate against cholera.
No commercially live vaccine against cholera caused by Vibrio cholerae O139 serogroup is available and it is currently needed. Virulent O139 strain CRC266 was genetically modified by firstly deleting multiple copies of the filamentous phage CTXφ, further tagging by insertion of the endoglucanase A coding gene from Clostridium thermocellum into the hemagglutinin/protease gene and finally deleting the mshA gene, just to improve the vaccine biosafety. One of the derived strains designated as TLP01 showed full attenuation and good colonizing capacity in the infant mouse cholera model, as well as highly immunogenic properties in the adult rabbit and rat models. Since TLP01 lacks MSHA fimbriae, it is refractory to infection with another filamentous phage VGJφ and therefore protected of acquiring CTXφ from a recombinant hybrid VGJφ/CTXφ. This strategy could reduce the possibilities of stable reversion to virulence out of the human gut. Furthermore, this vaccine strain was impaired to produce biofilms under certain culture conditions, which might have implications for the strain survival in natural settings contributing to vaccine biosafety as well. The above results has encouraged us to consider TLP01 as a live attenuated vaccine strain having an adequate performance in animal models, in terms of attenuation and immunogenicity, so that it fulfills the requirements to be evaluated in human volunteers.


Cocaine's use in ophthalmology: our 100-year heritage.
One hundred years ago the fledgling ophthalmologist Carl Koller demonstrated that the alkaloid cocaine was a local anesthetic suitable for rendering the eye temporarily insensible to pain. It was an event of historical significance, as his discovery opened the door not only to a new era in ophthalmic surgery, but to surgery in general. In this paper we review the ancient uses of the coca leaf, the historical events leading up to and following Koller's discovery, and the present day uses of cocaine in ophthalmology and medicine.


Efficacy of lower-body shielding in computed tomography fluoroscopy-guided interventions.
Computed tomography (CT) fluoroscopy-guided interventions pose relevant radiation exposure to the interventionalist. The goal of this study was to analyze the efficacy of lower-body shielding as a simple structural method for decreasing radiation dose to the interventionalist without limiting access to the patient. All examinations were performed with a 128-slice dual source CT scanner (12 × 1.2-mm collimation; 120 kV; and 20, 40, 60, and 80 mAs) and an Alderson-Rando phantom. Scatter radiation was measured with an ionization chamber and a digital dosimeter at standardized positions and heights with and without a lower-body lead shield (0.5-mm lead equivalent; Kenex, Harlow, UK). Dose decreases were computed for the different points of measurement. On average, lower-body shielding decreased scatter radiation by 38.2% within a 150-cm radius around the shielding. This decrease is most significant close to the gantry opening and at low heights of 50 and 100 cm above the floor with a maximum decrease of scatter radiation of 95.9% close to the scanner's isocentre. With increasing distance to the gantry opening, the effect decreased. There is almost no dose decrease effect at ≥150 above the floor. Scatter radiation and its decrease were linearly correlated with the tube current-time product (r (2) = 0.99), whereas percent scatter radiation decrease was independent of the tube current-time product. Lower-body shielding is an effective way to decrease radiation exposure to the interventionalist and should routinely be used in CT fluoroscopy-guided interventions.


A woman's influence to choose mastectomy as treatment for breast cancer.
Over a 10-y period at our community hospital, more than 50% of women 40 y of age and younger underwent a mastectomy as first line breast cancer treatment. These results catapulted a study to identify personal and physical implications of a mastectomy and to determine if, in women of all ages, breast conservation therapy with close follow-up is a better alternative to mastectomy. Six hundred eight women underwent a mastectomy for breast cancer from 1989 to 2005 at our teaching institution; 77% (n = 120) of 156 successfully contacted women agreed to participate in the study, and 70% (n = 84) of them completed a questionnaire. Most women discovered their breast cancer through mammography or self breast examination, 31% and 28%, respectively. Five patients were diagnosed at Stage 0, 35 at Stage 1, 26 at Stage 2, 8 at Stage 3, 1 at Stage 4, and 9 patients had an unknown stage of disease. Sixty-three patients primarily discussed their treatment plan with a surgeon; 80 were satisfied with the time spent discussing their treatment. Twenty-four patients underwent various reconstruction procedures; most (75%) were satisfied with their treatment and reconstruction choices. Mastectomy as a treatment choice for breast cancer did not have the negative personal and physical outcome that we had predicted. Personal choice and a surgeon's advice were the primary influencing factors on the women's treatment choice of mastectomy. Adequate preoperative discussion time and a multimodality cancer team can be most helpful in providing comprehensive treatment options for all women with breast cancer.


Revision surgery rates in chronic rhinosinusitis with nasal polyps: meta-analysis of risk factors.
Wide variations in revision endoscopic sinus surgery (ESS) rates for chronic rhinosinusitis with nasal polyposis (CRSwNP) have been reported. It is important to understand expected revision rates and factors that impact the need for revision. A literature search was conducted on PubMed, Scopus, and the Cochrane Database of Systematic Reviews. Following PRISMA guidelines, a systematic review and meta-analysis was performed on studies that reported revision surgery data for CRSwNP patients. Forty-five studies with 34,220 subjects were meta-analyzed, with an overall revision rate of 18.6% (95% confidence interval, 14.1%-23.6%). Studies with extractable follow-up data reported a mean revision rate of 16.2% over a weighted mean follow-up of 89.6 months. Factors associated with increased revision rates included allergic fungal rhinosinusitis (28.7%), aspirin-exacerbated respiratory disease (27.2%), asthma (22.6%), prior polypectomy (26.0%), and publication prior to 2008 (22.7%) (p < 0.05 for all). Although polyps can recur after ESS, reported long-term ESS revision rates are approximately 14% to 24%. Identifying risk factors for revision surgery can help manage patient expectations and determine optimal personalized treatments.


Transcutaneous Auricular Vagus Nerve Stimulation Attenuates Early Increases in Heart Rate Associated With the Cold Pressor Test.
Transcutaneous auricular vagus nerve stimulation (taVNS) may be useful in treating disorders characterized by chronic parasympathetic disinhibition. Acute taVNS decreases resting heart rate in healthy individuals, but little is known regarding the effects of taVNS on the cardiac response to an acute stressor. To investigate effects on the acute stress response, we investigated how taVNS affected heart rate changes during a cold pressor test (CPT), a validated stress induction technique that reliably elicits a sympathetic stress response with marked increases in heart rate, anxiety, stress, and pain. We recruited 24 healthy adults (ten women, mean age = 29 years) to participate in this randomized, crossover, exploratory trial. Each subject completed two taVNS treatments (one active, one sham) paired with CPTs in the same session. Order of active versus sham stimulation was randomized. Heart rate, along with ratings of anxiety, stress, and pain, was collected before, during, and after each round of taVNS/sham + CPT. In both stimulation conditions, heart rate was elevated from baseline in response to the CPT. Analyses also revealed a difference between active and sham taVNS during the first 40 seconds of the CPT (Δ heart rate [HR] = 12.75 ± 7.85 in the active condition; Δ HR = 16.09 ± 11.43 in the sham condition, p = 0.044). There were no significant differences in subjective ratings between active and sham taVNS. In this randomized, sham-controlled study, taVNS attenuated initial increases in HR in response to the CPT. Future studies are needed to investigate the effects of various taVNS doses and parameters on the CPT, in addition to other forms of stress induction. The Clinicaltrials.gov registration number for the study is NCT00113453.


Studies on the effect of dry Sundakai (Solanum torvum) powder supplementation on lipid profile, glycated proteins and amino acids in non-insulin dependent diabetic patients.
The effect of dry Sundakai powder supplementation (7 g providing 1.23 g of crude fibre) on glycemic control, lipidemic control, total amino acids and uronic acid was studied on 30 non-insulin dependent diabetes mellitus patients. All the patients were on hypoglycemic drugs. The above parameters were monitored at day 1, 15 and 30 days. After one month of fibre supplementation, no significant changes were observed with respect to glucose, lipid profile, glycated proteins, total amino acids and uronic acid levels in these subjects.


Mind-body therapy: attitudes, beliefs and practices of graduate faculty and students from accredited marriage and family therapy programs in the U.S. and Canada.
Interest in CAM and mind-body therapies (MBT) among mental health professionals has increased over the last decade. Individuals seeking treatment for mental health concerns often use MBTs and expect clinicians to be aware of such treatments. Yet, current data reveal a critical gap in training, practice, and the needs of those seeking treatment. To determine the attitudes, beliefs, and practices of marriage and family therapists regarding MBTs. Electronic survey method using Likert-type scale questions. Clinical faculty members and graduate students (N = 140) from accredited Marriage and Family Therapy programs in the United States and Canada. Findings revealed that a majority of respondents believed that graduate programs should introduce MBT topics during course of training and that MBTs are valuable in the treatment of various clinical problems. Respondents were familiar with at least one form of MBT and reported using such in personal and professional settings.


Isolation of N-phenylprotoporphyrin IX from the red cells and spleen of the phenylhydrazine-treated rat.
Blood and spleens of phenylhydrazine-injected rats were treated with a solution of acidic methanol and zinc ion to isolate a green pigment. The pigment was resolved into two, I and II, by thin-layer chromatography. Pigment I was a mixture of two isomers of zinc complex of esterified N-phenylprotoporphyrin IX, in which vinyl-substituted pyrrole rings A and B were phenylated; and pigment II was a mixture of two isomers of the porphyrin complex with the N-phenyl group on propionic acid-substituted rings C and D. These pigments were also chemically prepared from the reaction of phenylhydrazine with oxyhemoglobin, independently characterized, and used to confirm the structures of the biological pigments. Determination revealed that the total amount of pigments found in the blood and spleen at 24 h after injection of phenylhydrazine corresponds to about 0.4% of the injected phenylhydrazine.


Multimodal pain management in veterinary medicine: the physiologic basis of pharmacologic therapies.
Multimodal analgesia refers to the practice of combining multiple analgesic drug classes or techniques to target different points along the pain pathway in an effort to improve analgesia. This strategy requires an understanding of pain physiology and pathophysiology so pharmacologic interventions can be tailored to meet the needs of the patient. This article reviews the physiologic basis of pain as it relates to analgesic treatments and also introduces new developments in molecular biology that may guide analgesic drug development in the future.


PAH-sequestration capacity of granular and powder activated carbon amendments in soil, and their effects on earthworms and plants.
A field lysimeter study was carried out to investigate whether the amendment of 2% powder and granular activated carbon (PAC and GAC) to a soil with moderate PAH contamination had an impact on the PAH bioaccumulation of earthworms and plants, since AC is known to be a strong sorbent for organic pollutants. Furthermore, secondary effects of AC on plants and earthworms were studied through growth and nutrient uptake, and survival and weight gain. Additionally, the effect of AC amendments on soil characteristics like pH, water holding capacity, and the water retention curve of the soil were investigated. Results show that the amendment of 2% PAC had a negative effect on plant growth while the GAC increased the growth rate of plants. PAC was toxic to earthworms, demonstrated by a significant weight loss, while the results for GAC were less clear due to ambiguous results of a field and a parallel laboratory study. Both kinds of AC significantly reduced biota to soil accumulation factors (BSAFs) of PAHs in earthworms and plants. The GAC reduced the BSAFs of earthworms by an average of 47 ± 44% and the PAC amendment reduced them by 72 ± 19%. For the investigated plants the BSAFs were reduced by 46 ± 36% and 53 ± 22% by the GAC and PAC, respectively.


Imaging of Juvenile Idiopathic Arthritis.
Juvenile idiopathic arthritis is an umbrella term covering several distinct categories that share common features. The European League Against Rheumatism and the Pediatric Rheumatology European Society have published a consensus article with recommendations to guide radiologists and clinicians in choosing the best imaging technique for each particular clinical setting. A reproducible, accurate, validated, and long-established scoring system to use in everyday practice for monitoring and predicting long-term response to therapy is still to be developed on MR imaging for each joint.


The effect of storage temperature and physical state on the performance of antisera in radioimmunoassay after long-term storage.
The performance in radioimmunoassay of four antisera after storage at temperatures ranging from -40 degrees C to room temperature, in three physical states (frozen, liquid or freeze dried) was investigated over a 3-year period. No deterioration in antiserum performance in terms of precision and accuracy of quality control serum measurement or recovery of ligand was apparent under any of the storage conditions studied. Some lowering of titre became apparent in two of the antisera over the study period. Deterioration was most marked when antiserum was stored lyophilised at room temperature. Storage of antiserum frozen confers no advantage over storage at 4 degrees C provided precautions are taken to minimise bacterial contamination when storing antiserum in liquid form.


Changes in the metabolism of long chain fatty acids during adipose differentiation of 3T3 L1 cells.
A study was made of the kinetics of utilization of [9,10-3H]palmitate by 3T3 L1 cells undergoing slow spontaneous adipose differentiation and by a population of 3T3 L1 cells treated with 1-methylisobutylxanthine (MIX) and dexamethasone (DEX) to accelerate adipose differentiation. The results showed that, early in the course of the induced differentiation, the specific rate of beta-oxidation of long chain fatty acids (kappa 1) fell precipitously, particularly during the 2 days of exposure of the cells to MIX + DEX. The value of kappa 1 decreased slowly with the passage of time in untreated cells, a small proportion of which differentiated to adipocytes. In MIX + DEX-treated cells the abrupt decline in the rate of fatty acid oxidation was followed by a decrease in the rate of carnitine uptake. Both changes preceded the appearance of detectable alpha-glycerophosphate dehydrogenase activity, a sensitive indicator of adipose differentiation, and came well before the appearance of lipid droplets. Esterification was found to be the principal route of fatty acid utilization both by preadipocytes and by cells committed to adipose differentiation. With the passage of time, the specific rate of fatty acid esterification (kappa 2) increased by two-thirds in untreated cells but in the same period more than doubled in MIX + DEX-treated cells. Thus, while the ratio of kappa 2/kappa 1 rose in 9 days to 7.6 in untreated cells, it increased to 28.3 in treated cells. Measurements of the rate of lipolysis (kappa 3) showed no significant difference between preadipocytes and cells committed to adipose differentiation.


A year in the social life of a teenager: Within-person fluctuations in stress, phone communication, and anxiety and depression.
Stressful life events (SLEs) are strongly associated with the emergence of adolescent anxiety and depression, but the underlying mechanisms remain poorly understood, especially at the within-person level. We investigated how adolescent social communication (i.e., frequency of calls and texts) following SLEs relates to changes in internalizing symptoms in a multi-timescale intensive year-long study (N=30; n=355 monthly observations; n=~5,000 experience-sampling observations). Within-person increases in SLEs were associated with receiving more calls than usual at both monthly- and momentary-levels, and making more calls at the monthly-level. Increased calls were prospectively associated with worsening internalizing symptoms at the monthly-level only, suggesting that SLEs rapidly influences phone communication patterns, but these communication changes may have a more protracted, cumulative influence on internalizing symptoms. Finally, increased incoming calls prospectively mediated the association between SLEs and anxiety at the monthly-level. We identify adolescent social communication fluctuations as a potential mechanism conferring risk for stress-related internalizing psychopathology.


Factors Affecting Nutrition and Physical Activity Behaviors of Hispanic Families With Young Children: Implications for Obesity Policies and Programs.
To determine preferred policies and programs to prevent obesity and diabetes as identified by parents and caregivers of 3- to 5-year-old Latino children. Constructs from the Social Ecological Model were used to develop 10 focus group and key informant interview questions. Community venues and schools in St Paul, MN. A total of 64 parents and caregivers and 20 key informants provided comments. Community-based participatory research methods were used to gather opinions regarding appropriate and preferred methods to prevent obesity and diabetes among Latino youth. Native Spanish-speaking investigators who were members of the community conducted 7 focus groups (60-90 minutes each) and 20 key informant interviews. Themes and subthemes of preferences based on participant comments. Transcript-based, long-table qualitative analysis. Five themes were identified: (1) cultural beliefs and practices are inconsistent with obesity prevention; (2) cost and convenience; (3) positive parenting practices; (4) we want to learn more about being healthy; and (5) gardens, parks, gyms, and school meals. At least 1 theme fell within each of the Social Ecological Model domains. Our results suggest that parents of young Hispanic children prefer that obesity and diabetes prevention programs address multiple levels of influence.


Is patient age a factor in the occurrence of prostate-specific antigen bounce phenomenon after external beam radiotherapy for prostate cancer?
To evaluate the effect of patient age on the occurrence of prostate-specific antigen (PSA) "bounce" after external beam radiotherapy (EBRT) for prostate cancer. In this study, 964 patients received EBRT alone for prostate cancer between April 1987 and January 1998 who had been followed for at least 12 months. Prostate-specific antigen values were obtained every 3 to 6 months after radiotherapy. Median overall follow-up was 48 months. Prostate-specific antigen bounce was defined as an initial increase in serum PSA of at least 0.5 ng/mL, followed by a decrease to prebounce baseline serum PSA values, all within 60 months after EBRT. Biochemical failure was defined as three consecutive increases in posttreatment PSA concentration after achieving a nadir. Multivariate Cox regression analysis was performed to evaluate the influences of age, pretreatment PSA concentration, Gleason score (determined at biopsy), clinical T stage classification, and radiation dose on PSA bounce-free survival and biochemical disease-free survival, with P < 0.05 considered statistically significant. Twelve percent of the patients developed a PSA bounce. Age was not associated with the occurrence of a PSA bounce (P = 0.63), the magnitude of the PSA bounce (P = 0.90), or the duration of the PSA bounce (P = 0.39). Patients who had PSA bounce had a statistically significant higher biochemical disease-free survival than those who did not (P = 0.00004). In our study, age was not predictive of PSA bounce. However, younger patients with a rising PSA after radiotherapy should be followed closely for evidence of biochemical failure.


Galcanezumab treatment changes visual related EEG connectivity patterns in migraine patients.
Monoclonal antibodies against calcitonin gene-related peptides (CGRP) are innovative therapies for migraine treatment. Although they are clinically effective, how anti-CGRP treatment reduces migraine attacks still remains unclear. In this observational case-control study, we aimed to apply graph theory to EEG data from 20 migraine patients and 10 controls to investigate the effects of 3 months of galcanezumab on brain connectivity. We analyzed EEG rhythms during black-white pattern reversal stimulation with 0.5 cycle per degree spatial frequency before (T0) galcanezumab injection, as well as after 3 months (T2). EEG recordings made 1 hour after galcanezumab administration served as the control session (T1). Patients' connectivity patterns obtained at T0, T1 and T2 were compared with normal controls. We found that galcanezumab increased network integration (with a 5% significance level corrected with the false discovery rate), changing the intensity of connections between the occipital through the frontal areas. At 3 months follow up, patients with persistent high headache intensity had a minor effect on the strength of connections (evaluated using Kendall's rank correlation test and p < 0.05). The potent anti-nociceptive action that galcanezumab exerts at a peripheral level could restore cortical connections and possibly factors predisposing to attack onset.


Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma.
To evaluate pleurectomy/decortication (P/D) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM). In a retrospective review, we included MPM patients treated with P/D and adjuvant RT at Memorial Sloan-Kettering Cancer Center from 1974 to 2003. When indicated, patients received intraoperative brachytherapy to residual tumor. All 123 patients received external beam RT (median dose, 42.5 Gy; range, 7.2-67.8 Gy) to the ipsilateral hemithorax postoperatively. Fifty-four patients underwent brachytherapy (matched peripheral dose, 160 Gy). The median and 2-year overall survival for all patients was 13.5 months (range, 1-199 months) and 23%, respectively. One-year actuarial local control for all patients was 42%. Multivariate analysis for overall survival revealed radiation dose <40 Gy (p = 0.001), nonepithelioid histology (p = 0.002), left-sided disease (p = 0.01), and the use of an implant (p = 0.02) to be unfavorable. Two patients (1.6%) died from Grade 5 toxicity within 1 month of treatment. Pleurectomy/decortication with adjuvant radiotherapy is not an effective treatment option for patients with MPM. Our results imply that residual disease cannot be eradicated with external RT with or without brachytherapy and that a more extensive surgery followed by external RT might be required to improve local control and overall survival.


Effects of compositions of dimethyl-beta-cyclodextrins on enantiomer separations by cyclodextrin modified capillary zone electrophoresis.
In enantiomeric separation by capillary zone electrophoresis using dimethyl-beta-cyclodextrin (DM-beta-CD) as a chiral selector, enantioselectivities were sometimes significantly different among DM-beta-CDs from five different suppliers. The reason was due to the difference in the compositions among these commercial products, which was shown by the liquid chromatographic (LC) analysis. As for commercial DM-beta-CD from one supplier, two major components were obtained by preparative LC. NMR spectroscopic and mass spectrometric analyses of these two components were performed to estimate the structure of each component. The results implied that the commercial products consist of heptakis(2,6-di-O-dimethyl)-beta-CD and hexakis(2,6-di-O-methyl)-mono(2,3,6-tri-O-methyl)-beta-CD. Sometimes different enantioselectivities were observed between these two components including the original DM-beta-CD.


Dynamics of plosive consonants via imaging, computations, and soft electronics.
A quantitative understanding of the coupled dynamics of flow and particles in aerosol and droplet transmission associated with speech remains elusive. Here, we summarize an effort that integrates insights into flow-particle dynamics induced by the production plosive sounds during speech with skin-integrated electronic systems for monitoring the production of these sounds. In particular, we uncover diffusive and ballistic regimes separated by a threshold particle size and characterize the Lagrangian acceleration and pair dispersion. Lagrangian dynamics of the particles in the diffusive regime exhibit features of isotropic turbulence. These fundamental findings highlight the value in skin-interfaced wireless sensors for continuously measuring critical speech patterns in clinical settings, work environments, and the home, based on unique neck biomechanics associated with the generation of plosive sounds. We introduce a wireless, soft device that captures these motions to enable detection of plosive sounds in multiple languages through a convolutional neural network approach. This work spans fundamental flow-particle physics to soft electronic technology, with implications in monitoring and studying critical speech patterns associated with aerosol and droplet transmissions relevant to the spread of infectious diseases.


Temporal and spatial preferences of c-fos mRNA expression in the rat brain following cortical lesion.
The expression of the proto-oncogene c-fos is increased in neuronal cells by a number of stimuli and the usefulness of this gene as a marker of neuronal activity has been demonstrated. The temporal and spatial expression of c-fos mRNA following the induction of a unilateral cortical lesion have been investigated in the rat brain by Northern blot analysis and in situ hybridization histochemistry. It was observed that the lesion evoked a rapid increase (20-fold) in the content of c-fos mRNA in the ipsilateral cortex, whereas in the contralateral cortex c-fos mRNA expression was more modest (7-fold). In the whole hippocampus a large and very rapid increase (17-fold) of c-fos mRNA expression was detected. The effect of a cortical lesion on Ca2+ uptake and membrane potential was also investigated. Using synaptosomes as a model system, we have provided evidence that Ca2+ entry via membrane depolarization increases in coordination with c-fos gene expression in neuronal cells. The principal conclusions from this study are that cortical lesions induce transient expression of the c-fos gene in specific neuronal cells of the rat brain.


Three algorithms and SAS macros for estimating power and sample size for logistic models with one or more independent variables of interest in the presence of covariates.
Commonly when designing studies, researchers propose to measure several independent variables in a regression model, a subset of which are identified as the main variables of interest while the rest are retained in a model as covariates or confounders. Power for linear regression in this setting can be calculated using SAS PROC POWER. There exists a void in estimating power for the logistic regression models in the same setting. Currently, an approach that calculates power for only one variable of interest in the presence of other covariates for logistic regression is in common use and works well for this special case. In this paper we propose three related algorithms along with corresponding SAS macros that extend power estimation for one or more primary variables of interest in the presence of some confounders. The three proposed empirical algorithms employ likelihood ratio test to provide a user with either a power estimate for a given sample size, a quick sample size estimate for a given power, and an approximate power curve for a range of sample sizes. A user can specify odds ratios for a combination of binary, uniform and standard normal independent variables of interest, and or remaining covariates/confounders in the model, along with a correlation between variables. These user friendly algorithms and macro tools are a promising solution that can fill the void for estimation of power for logistic regression when multiple independent variables are of interest, in the presence of additional covariates in the model.


Trends in Utilization and Cost of Inpatient Spinal Cord Stimulation: Analysis of Data from 2008 to 2014.
In this study, we sought to characterize contemporary trends in cost and utilization of spinal cord stimulation (SCS). The Healthcare Cost and Utilization Project-National Inpatient Sample was queried for inpatient admissions from 2008 to 2014 where SCS was performed. We then determined the rates and costs of SCS performed in this time frame to treat diagnoses that we classified as device-related complications, degenerative spine disease, pain syndromes, and neuropathies/neuritis/nerve lesions. Least-squares regression was performed to determine the yearly trends for each indication adjusted by the total number of yearly hospitalizations for that diagnosis. We identified a total of 6876 admissions in whom an SCS was performed. The overall rate of inpatient SCS procedures performed has decreased by 45% from 2008 to 2014 (14.0 to 7.7 procedures per 100,000 admissions). Adjusted analysis for yearly trends also demonstrated a declining trend for all indications; however, this was not found to be statistically significant, except for device-related complications (P = 0.004). The median inflation-adjusted cost of an admission where SCS was performed increased slightly by 7.4% from $26,200 (IQR: $16,700-$33,800) in 2008 to $28,100 (IQR: $19,600-$36,900) in 2014. Billed hospital charges demonstrated a significant increase with median inflation-adjusted admission charge of $66,068 in 2008 to $110,672 in 2014. Despite a declining contemporary trend in inpatient SCS, an increase was noted in admission costs and hospital charges. A significant declining trend was noted in revision SCS implantations due to device-related complications.


Modeled temperature dependencies of macromolecular allocation and elemental stoichiometry in phytoplankton.
Warming oceans may affect how phytoplankton allocate nutrients to essential cellular processes. Despite the potential impact of such processes on future biogeochemical cycles, questions remain about how temperature affects macromolecular allocation and elemental stoichiometry within phytoplankton cells. Here, we present a macromolecular model of phytoplankton and the effect of increasing temperature on the intracellular allocation of nutrients at a constant growth rate. When temperature increases under nitrogen (N) and phosphorus (P) co-limitation, the model shows less investment in phosphorus-rich RNA molecules relative to nitrogen-rich proteins, leading to a more severe decrease in cellular P:C than N:C causing increased cellular N:P values. Under P limitation, the model shows a similar pattern, but when excess P is available under N limitation, we predict lowered N:P due to the effect of luxury uptake of P. We reflected our model result on the surface ocean showing similar latitudinal patterns in N:P and P:C to observation and other model predictions, suggesting a considerable impact of temperature on constraining the elemental stoichiometry in the ocean.


Speech performance in pediatric users of Nurotron ® Venus™ cochlear implants.
The primary purpose of this study was to investigate the longitudinal speech performance over 3 years in pediatric users of the Nurotron(®) cochlear implant system. The secondary purpose was to compare the speech performances of younger and older children with cochlear implants (CIs). The Mandarin Early Speech Perception (MESP), Meaningful Use of Speech Scale (MUSS), and Putonghua Chinese Communicative Development Inventory (PCDI) were used to evaluate speech performance of 22 Mandarin-speaking pediatric CI users throughout the first 36 months post-implantation. The subjects were grouped according to the age at implantation, i.e., younger CI group (<3 years) and older CI group (>3 years). All the subjects demonstrated improvement in speech performance throughout the first 3 years of implant use with mean scores reaching the maximum performance at 36 months post-implantation. The median categories of MESP increased from 0.23 pre-implantation to 5.57 three years post-implantation. Likewise, the median percentage of MUSS was 5.57% to 73.75%; the median performance of PCDI was 55 to 400 for PCDI-comprehension and 32 to 384 for PCDI-production at the same interval. At nearly all test intervals, the older group performed better than the younger group except 24 months post-implantation, at which the MUSS score of the younger CI group was higher than that of the older CI group. The children with Nurotron(®) Venus™ CI system showed considerable gains in speech and language development including tone performance which improved with hearing age. Earlier implantations haven't presented significantly positive performances until 24 months post-implantation in all the tests.


Daunomycin-arachidonic acid complex as a potential new antitumor agent.
A daunomycin-arachidonic acid complex (DM-C20:4) administered IV had a marked antitumor effect on the intraperitoneal growth of the AFP-producing hepatoma cell line, AH66. However, the daunomycin-arachidic acid (DM-C20:0) saturated fatty acid complex showed only the same antitumor effect on the AH66 cells as free daunomycin. It was demonstrated that the DM-C20:4 preparation maintained its chemical properties for some time in both plasma and liver homogenate.


Direct projections from the dorsal premotor cortex to the superior colliculus in the macaque (macaca mulatta).
The dorsal premotor cortex (PMd) is part of the cortical network for arm movements during reach-related behavior. Here we investigate the neuronal projections from the PMd to the midbrain superior colliculus (SC), which also contains reach-related neurons, to investigate how the SC integrates into a cortico-subcortical network responsible for initiation and modulation of goal-directed arm movements. By using anterograde transport of neuronal tracers, we found that the PMd projects most strongly to the deep layers of the lateral part of the SC and the underlying reticular formation corresponding to locations where reach-related neurons have been recorded, and from where descending tectofugal projections arise. A somewhat weaker projection targets the intermediate layers of the SC. By contrast, terminals originating from prearcuate area 8 mainly project to the intermediate layers of the SC. Thus, this projection pattern strengthens the view that different compartments in the SC are involved in the control of gaze and in the control or modulation of reaching movements. The PMD-SC projection assists in the participation of the SC in the skeletomotor system and provides the PMd with a parallel path to elicit forelimb movements.


FISH on sperm: spot-counting to stop counting? Not yet.
To evaluate the reliability and applicability of the spot-counting system (Cytovision Spot AX workstation) which offers an alternative to the tedious manual analysis of sperm fluorescence in situ hybridization (FISH). Manual and automatic analyses were performed and compared. Universitat Autònoma de Barcelona. Twenty-four men who asked for information on infertility showing different seminal parameters. A semen sample for each patient was collected and prepared for FISH. A dual-color FISH using specific probes for chromosomes 13 and 21 and a triple-color FISH with centromeric probes for chromosomes 18, X, and Y were used (Vysis). Standard FISH analysis was carried out. Automatic analysis was subsequently performed using a Spot AX system. Overall, we performed 120 comparisons. In 116 out of 120 (96.67%), the percentage of anomalies reported using manual counting fell within the incidence detected using the automatic system. In the remaining comparisons, statistical differences were detected (4 out of 120; 3.33%). Time consumed by the automatic analysis was always higher than the manual one, being influenced by the characteristics of the preparations. The spot-counting system has potential, but before the service is ready to be offered, we still need to overcome some limitations associated with it.


Corrigendum: Long Non-Coding RNA AL513318.2 as ceRNA Binding to hsa-miR-26a-5p Upregulates SLC6A8 Expression and Predicts Poor Prognosis in Non-Small Lung Cancer.
[This corrects the article DOI: 10.3389/fonc.2022.781903.].


Motilin, vasoactive intestinal peptide and gastrin in infantile colic.
Intestinal hyperperistalsis is one part of the clinical picture in infantile colic. Three gut hormones involved in the regulation of gut motility; motilin, vasoactive intestinal peptide (VIP) and gastrin, were measured with the RIA method in: 40 infants with infantile colic, (age 2-22 weeks), 42 healthy age-matched infants, 11 children (age 3-36 months) with gastrointestinal disorders, and 20 children (age 3-36 months) with non-gastrointestinal disorder. Basal s-motilin levels were raised in infants with infantile colic (p less than 0.01) and in children with other gastrointestinal disorders (p less than 0.001). Formula-fed infants had higher basal s-motilin levels than the breast-fed infants (p less than 0.05). P-VIP and s-gastrin levels were raised in children with other gastro-intestinal disorders (p less than 0.05), but not in infantile colic. Formula-fed colicky infants had higher s-gastrin levels than the breast-fed colicky infants (p less than 0.05). We suggest that the increased s-motilin level in infantile colic might account in part for the clinical picture of this disorder.


A novel auxin-inducible degron system for rapid, cell cycle-specific targeted proteolysis.
The discrimination of protein biological functions in different phases of the cell cycle is limited by the lack of experimental approaches that do not require pre-treatment with compounds affecting the cell cycle progression. Therefore, potential cycle-specific biological functions of a protein of interest could be biased by the effects of cell treatments. The OsTIR1/auxin-inducible degron (AID) system allows "on demand" selective and reversible protein degradation upon exposure to the phytohormone auxin. In the current format, this technology does not allow to study the effect of acute protein depletion selectively in one phase of the cell cycle, as auxin similarly affects all the treated cells irrespectively of their proliferation status. Therefore, the AID system requires coupling with cell synchronization techniques, which can alter the basal biological status of the studied cell population, as with previously available approaches. Here, we introduce a new AID system to Regulate OsTIR1 Levels based on the Cell Cycle Status (ROLECCS system), which induces proteolysis of both exogenously transfected and endogenous gene-edited targets in specific phases of the cell cycle. We validated the ROLECCS technology by down regulating the protein levels of TP53, one of the most studied tumor suppressor genes, with a widely known role in cell cycle progression. By using our novel tool, we observed that TP53 degradation is associated with increased number of micronuclei, and this phenotype is specifically achieved when TP53 is lost in S/G2/M phases of the cell cycle, but not in G1. Therefore, we propose the use of the ROLECCS system as a new improved way of studying the differential roles that target proteins may have in specific phases of the cell cycle.


Conformational probes for elucidating the nature of substance P binding to the NK1 receptor: initial efforts to map the Phe7-Phe8 region.
Three substance P analogs with conformation constraints in the Phe7-Phe8 region have been prepared in connection with an effort to differentiate two families of potential conformations for the binding of substance P to its NK1 receptor. While the analogs did not bind the NK1 receptor with high affinity, the synthesis of the analogs demonstrated the utility of a general method for constructing piperazinone based peptidomimetics.