Short communication: effectiveness of sample duplication to control error in ruminant digestion studies.
Eight ruminally cannulated lactating dairy cows from a study on the effect of dietary rumen-degraded protein on production and digestion of nutrients were used to assess using sample duplication to control day-to-day variation within animals and errors associated with sampling and laboratory analyses. Two consecutive pooled omasal samples, each representing a feeding cycle, were obtained from each cow in each period. The effectiveness of sample duplication in error control was tested by comparing the variance of the difference in treatment means when taking 2 samples from each cow in each period to the variance when taking only one sample. Compared with no duplication, sample duplication improved precision by reducing variance by 50, 40, 31, 23, 23, and 9% for, respectively, rumen-undegraded protein flows, ruminal neutral detergent fiber digestibility, microbial nonammonia N flow, microbial efficiency, organic matter flow, and organic matter truly digested in the rumen. For these same variables, reductions in the standard errors of the difference between treatment means due to sample duplication represented 100, 87, 73, 59, 58, and 27% of the predicted reductions resulting from doubling the number of experimental units without sample duplication. Sample duplication can substantially reduce experimental error originating from day-to-day variation within cows, sample collection, and laboratory analyses, thus improving statistical power in ruminant digestion studies.


Diversity and Classification of Genetic Variations in Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is a neurodevelopmental condition with symptoms that affect the whole personality and all aspects of life. Although there is a high degree of heterogeneity in both its etiology and its characteristic behavioral patterns, the disorder is well-captured along the autistic triad. Currently, ASD status can be confirmed following an assessment of behavioral features, but there is a growing emphasis on conceptualizing autism as a spectrum, which allows for establishing a diagnosis based on the level of support need, free of discrete categories. Since ASD has a high genetic predominance, the number of genetic variations identified in the background of the condition is increasing exponentially as genetic testing methods are rapidly evolving. However, due to the huge amount of data to be analyzed, grouping the different DNA variations is still challenging. Therefore, in the present review, a multidimensional classification scheme was developed to accommodate most of the currently known genetic variants associated with autism. Genetic variations have been grouped according to six criteria (extent, time of onset, information content, frequency, number of genes involved, inheritance pattern), which are themselves not discrete categories, but form a coherent continuum in line with the autism spectrum approach.


Mental health and factors related to life satisfaction in nursing home and community-dwelling older adults during COVID-19 pandemic in Turkey.
The geriatric population is supposed to be at high risk for psychological distress as well as adverse outcomes and mortality during the COVID-19 pandemic. This study aimed to investigate the levels of depression, anxiety, death anxiety and life satisfaction levels and factors related to life satisfaction in individuals aged 65 years and older during the pandemic and to compare these variables between nursing home (NH) and community-dwelling older adults. This study has a cross-sectional and descriptive design, and a total of 133 nursing NH and community-dwelling older adults were enrolled in the study. Turkish death anxiety scale (TDAS), life satisfaction scale (SLS) and depression anxiety stress scale-21 (DASS-21) were used for the assessment. The majority of the older adults had no or mild depression, anxiety and stress symptoms in spite of the prolonged confinements, and were slightly satisfied with their lives. However, depression, anxiety, stress and TDAS levels were higher in participants aged 80 years and older. Residents of NHs had higher TDAS, depression and anxiety levels and lower SLS levels than community-dwelling older adults. Participants who were meeting their children and/or grandchildren less than 2 h a week, were found to have significantly lower SLS and higher depression scores. The increase in depression and TDAS scores predicted a decrease in SLS scores in older adults. As NH resident older adults have higher psychological distress and decreased life satisfaction due to the social isolation caused by the prolonged confinements, NH staff should be regularly informed on both preventive measures and mental health consequences of the pandemic, and should be trained for basic therapeutic interventions. Older adults should be supported to use telecommunication technologies to contact their families and friends, and participate in safe and accessible person-centred activity programs.


[Proposal for a predictive clinical scale in dysphagia].
The compiling of a predictive clinical scoring system for the risk of a false passage (FP) has its origins in the limitations of tests which explore only the cough reflex, known to be absent or faulty in 40% of patients investigated for problems of deglutition. A raised clinical score is based on the results of an exhaustive prospective study of 140 patients tested for the first time by videofluoroscopy for FP, this being the reference investigation for false passages. Discriminant analysis allowed the most selective variables to be identified and retained. We have identified 2 categories of patients, according to whether or not they have had any ENT past history. The score is obtained by adding the weighted values for the selected clinical signs. For those patients with an ENT past history, 5 clinical variables were retained: the absence of adhesions = 14, the presence of a velar reflex = 8, the capacity for voluntary deglutition = 8, glottic obstruction = 6, the absence of primitive reflexes = 6, giving a total score for the variables of between 0 and 42. If the total exceeds 32 or is less than 26, there is no FP; for scores between 32 and 26, videofluoroscopy is required to give more precise evidence of the risk. When this scoring system was applied prospectively to a series of 105 patients, a correct predictive result was obtained in 54 patients (51.4%), an equivocal result in 42 patients (40%), and a false result in 9 patients (8.6%), 3 of which (2.8%) were false negatives. The predictive score for FP allows evaluation of the risks of FP in at-risk patients, and adaptation of the treatment strategy according to the type of disordered physiology expected from the cause; thus videofluoroscopy can then be reserved for cases where treatment fails, so that the precise deglutition problem can be pinpointed.


Sodium Carbonate-Promoted Formation of 5-Amino-1,2,4-thiadiazoles and 5-Amino-1,2,4-selenadiazoles with Elemental Sulfur and Selenium.
Sodium carbonate-promoted facile synthesis of 5-amino-1,2,4-thiadiazoles and 5-amino-1,2,4-selenadiazoles with elemental sulfur and selenium, respectively, was developed. This method was carried out with O2 in the air as the green oxidant, and it has several advantages, including low cost, low toxicity, and stable sulfur and selenium sources, good to excellent yields with water as the sole byproduct, simple operation, and a broad substrate scope. Preliminary mechanistic studies indicate that the formation of the 1,2,4-thiadiazole ring and the 1,2,4-selenadiazole ring undergoes different processes.


Interventions for mitigating occupational stress for professional dementia caregivers in residential aged care: A systematic review with meta-analysis.
Occupational stress in professional dementia caregivers in residential aged care facilities has adverse effects on care quality, caregivers' health, and workforce sustainability. The purpose of this study was to examine the evidence regarding interventions to mitigate occupational stress for this population. A systematic review of CINAHL, PsycINFO, PubMed and MEDLINE databases was conducted to identify original RCT research reporting on stress interventions, published in English between 1995 and March 2022. Search results were screened by two independent reviewers. Quality and risk of bias were appraised using the Downs and Black Checklist and Risk of Bias by two reviewers. Meta-analysis and subgroup analysis examined the pooled intervention effects on stress compared to control. 10 studies met the inclusion criteria, and these reported on 15 interventions and 28 outcomes from 92 facilities, involving 1,397 caregivers. We found a small and insignificant effect of interventions on caregiver stress (g = -.27, p = .16). Heterogeneity was partially explained by subgroup analysis. Interventions can mitigate stress and burden not attributed to client behaviour (n = 3) (g = -.85, p < .001), and improve caregivers' self-efficacy (n = 4) (g = -.35, p = .07). We were unable to determine the most effective type of intervention, although organisation focused interventions showed the greatest potential (g = -.58, p = .08). Interventions that improve caregivers' personal and organisational resources can reduce non-client associated stress and burden and increase self-efficacy. Aged care providers are recommended to prioritise education with organisational support interventions. Research on longitudinal effects and high-risk caregivers is required. Limitations are discussed. CRD42022313715 (registered April 2022).


Reaching the poor through community-based distributors of contraceptives: experiences from Muheza district, Tanzania.
Community based distribution (CBD) programmes were introduced as a strategy to ensure access of contraceptives to the needy. The strategy is reported to increase contraceptive knowledge and use. Although CBD agents have the advantage of reaching the poor in rural areas, wealth gap does exist even in these settings. The objective of this study was to determine access to information and modern contraceptives services among people of different wealth status in a rural setting in Muheza, Tanzania. This cross-sectional study was conducted following a six year project in promotion of contraceptive using community-based agents. The study area was stratified into three socio-geographical strata from which one village was randomly selected. Through house-to-house visits, interviews were conducted using structured questionnaires until the required sample size was obtained. A community-led wealth ranking criteria was developed through consensus and used to classify respondents into wealth categories. A total of 1,420 respondents were interviewed. Contraceptive Prevalence Rate (CPR) for modern methods was 32.2%; injectables accounted for half (50.8%) followed by pills (32.7%). CBD agents accounted for one-third (34.3%) of the contraceptive use. There was no difference in the access to information (P=0.44) and to contraceptives (P=0.83) between the poorer and the less poor. Half of the respondents (49.4%; 214/431) reported paying for services, with no difference between the less poor and the poorer (P=0.75). Respondents receiving services from health facilities were more likely to pay for services (61.3%) compared to CBD agents (25.0%). However, the level of satisfaction was high (approximately 70%) in both health facilities and CBD agents. This study has shown that people in the rural settings of Muheza district were able to access information and contraceptives from CBD agents and health facilities, regardless of their wealth status. There is however, need to address the issue of informal payments lest it deters people in need from accessing the services.


Reading through a noisy channel: why there's nothing special about the perception of orthography.
The goal of research on how letter identity and order are perceived during reading is often characterized as one of "cracking the orthographic code." Here, we suggest that there is no orthographic code to crack: Words are perceived and represented as sequences of letters, just as in a dictionary. Indeed, words are perceived and represented in exactly the same way as other visual objects. The phenomena that have been taken as evidence for specialized orthographic representations can be explained by assuming that perception involves recovering information that has passed through a noisy channel: the early stages of visual perception. The noisy channel introduces uncertainty into letter identity, letter order, and even whether letters are present or absent. We develop a computational model based on this simple principle and show that it can accurately simulate lexical decision data from the lexicon projects in English, French, and Dutch, along with masked priming data that have been taken as evidence for specialized orthographic representations.


Visible light communications: increasing data rates with polarization division multiplexing.
In this Letter, we propose a new configuration for visible light communication systems, which results in doubling of the data rate due to the use of polarization division multiplexing. As light-emitting diodes are unpolarized incoherent light sources, we isolate both the perpendicular s and parallel p modes for independent modulation. For the first time, to the best of our knowledge, we show that it is possible to transmit and successfully recover two separate orthogonal frequency division multiplexing (OFDM) signals on each polarization (pol-OFDM). Furthermore, we compare the performance of the pol-OFDM system with the transmission of a single conventional OFDM signal without a polarizer over the same physical link. We show that similar bit error rates can be achieved while obtaining ∼45% improvement in both the data rate and spectral efficiency due to polarization multiplexing.


Deafness disrupts chloride transporter function and inhibitory synaptic transmission.
Loss of sensory function leads to atrophy or death within the developing CNS, yet little is known about the physiology of remaining synapses. After bilateral deafening, gramicidin-perforated-patch recordings were obtained from gerbil inferior colliculus neurons in a brain slice preparation. Afferent-evoked IPSPs had a diminished ability to block current-evoked action potentials in deafened neurons. This change could be attributed, in part, to a loss of potassium-dependent chloride transport function, with little change in K-Cl cotransporter expression. Treatments that suppressed chloride cotransport (bumetanide, cesium, and genistein) had little or no effect on neurons from deafened animals. These same treatments depolarized the E(IPSC) of control neurons. Semiquantitative RT-PCR and immunohistochemical staining indicated no change in the expression of chloride cotransporter mRNA or protein after deafness. Therefore, profound hearing loss leads rapidly to the disruption of chloride homeostasis, which is likely attributable to the dysfunction of the potassium-dependent chloride cotransport mechanism, rather than a downregulation of its expression. This results in inhibitory synapses that are less able to block excitatory events.


Modified regional self-interaction correction method based on the pseudospectral method.
A modification of the regional self-interaction correction (RSIC) scheme (Tsuneda et al., J. Comput. Chem. 2003, 24, 1592), pseudospectral RSIC (PSRSIC), is proposed to eliminate the self-interaction errors (SIEs) especially in core regions. PSRSIC reduces the SIEs by substituting the HF exchange energy density calculated with the use of the pseudospectral technique for the exchange energy in the SI-domain region. PSRSIC is combined with the long-range correction (LC) scheme. TDDFT calculations with LC-PSRSIC yield all of the core-, valence-, Rydberg-, and charge-transfer-excitation energies with reasonable accuracy. Core-ionization energies are also well-reproduced by LC-PSRSIC.


Interactions between Streptococcus suis serotype 2 and different epithelial cell lines.
Streptococcus suis is an important swine pathogen responsible for cases of sudden death, septicaemia, meningitis, endocarditis and pneumonia. It is also recognized as a zoonotic agent in people occupationally exposed to pigs or pig products. Knowledge on virulence factors of S. suis serotype 2 is limited and the pathogenesis of the infection is poorly understood. It has been suggested that the disease due to S. suis serotype 2 begins with colonization of the nasopharyngeal epithelium, followed by either spread within the respiratory tract or invasion of the bloodstream. The mechanisms involved in the access of bacteria from the bloodstream to the central nervous system are unknown. It is possible that epithelial cells of the choroid plexus also play an important role in the pathogenesis of the meningitis. Different interactions (adhesion, invasion and toxic effects) of S. suis serotype 2 with epithelial cell lines [LLC-PK1, PK(15), A549, HeLa and MDCK] were studied and compared to those of a human pathogen which also causes meningitis, group B Streptococcus (GBS). The results showed that S. suis serotype 2, in contrast to GBS, is able to adhere to but not to invade epithelial cells. The adhesin(s) involved seem(s) to be partially masked by the capsule and are a part of the cell wall. The haemolysin produced by S. suis serotype 2 is responsible for a toxic effect observed on epithelial cells. The results described give additional evidence that pathogenesis of the infection differs between S. suis and GBS. In particular, it is possible that suilysin-positive S. suis strains use adherence and cell injury, as opposed to direct cellular invasion, as part of a complicated multistep process which leads to bacteraemia and meningitis in pigs.


An unusual surgical site infection in a liver transplant recipient.
Mycobacterium abscessus is a rare cause of human infection and is difficult to diagnose unless it is suspected. A 45-year-old woman underwent deceased donor liver transplantation following which she developed non-healing surgical site infection, which did not resolve with routine antibiotics for 2 months. The scraping of the wound revealed M abscessus infection. Definitive identification of this species of mycobacterium was possible by its growth characteristics on culture and reverse line blot hybridisation assay. She was treated with clarithromycin and cotrimaxazole as per sensitivity and showed complete recovery from the infection within 6 weeks of starting the drugs, which were continued for 6 months. We believe that this is the first documented case of surgical site infection by M abscessus in a liver transplant recipient.


WD40 repeat domain proteins: a novel target class?
Antagonism of protein-protein interactions (PPIs) with small molecules is becoming more feasible as a therapeutic approach. Successful PPI inhibitors tend to target proteins containing deep peptide-binding grooves or pockets rather than the more common large, flat protein interaction surfaces. Here, we review one of the most abundant PPI domains in the human proteome, the WD40 repeat (WDR) domain, which has a central peptide-binding pocket and is a member of the β-propeller domain-containing protein family. Recently, two WDR domain-containing proteins, WDR5 and EED, as well as other β-propeller domains have been successfully targeted by potent, specific, cell-active, drug-like chemical probes. Could WDR domains be a novel target class for drug discovery? Although the research is at an early stage and therefore not clinically validated, cautious optimism is justified, as WDR domain-containing proteins are involved in multiple disease-associated pathways. The druggability and structural diversity of WDR domain binding pockets suggest that understanding how to target this prevalent domain class will open up areas of disease biology that have so far resisted drug discovery efforts.


Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique: implications for patients with breast cancer.
To assess our long-term complications from complete axillary lymph node dissection (AXLND) in patients with breast cancer. Complete AXLND as part of the surgical therapy for breast cancer has come under increased scrutiny due the use of the sentinel lymph node (SLN) biopsy technique to assess the status of the axillary nodes. As the enthusiasm for the SLN technique has increased, our impression has been that the perceived complication rate from AXLND has increased dramatically while the negative aspects of the SLN technique have been underemphasized. Female patients seen in routine follow-up over a 1-year period were eligible for our retrospective study of the long-term complications from AXLND if they were a minimum of 1 year out from all primary therapy; ie, surgery, radiation, and/or chemotherapy. All patients had previously undergone either a modified radical mastectomy (MRM) or a segmental mastectomy with axillary dissection and postoperative radiation (SegAx/XRT). All patients had a Level I-III dissection. Objective measurements, including upper and lower arm circumferences and body mass index (BMI), were obtained, and a subjective evaluation from the patients was conducted. Ninety-four patients were eligible for our study; 44 had undergone MRM, and 50 had undergone SegAx/XRT. The average number of nodes removed was 25.6 (standard deviation, 8). Thirty-three percent of the patients had positive nodal disease, 95% of the patients had an upper arm circumference within 2 cm of the unaffected side, and 93.3% had a lower arm circumference within 2 cm of the unaffected side. Subjectively, 90.4% of the patients had either no or minimal arm swelling, and 96.8% of the patients had "good" or "excellent" overall arm function. The most common long-term symptom was numbness involving the upper, inner aspect of the affected arm (25.5%). Our data indicate that a complete AXLND can be performed with minimal long-term morbidity. The lower the morbidity of AXLND, the less acceptable are the unique complications of the SLN technique.


[Tactics of surgical treatment of degenerative-dystrophic lesions of the lumbosacral spine in case of HIP-SPINE-syndrome].
The objective of this study is definition of surgical treatment tactics of multilevel degenerative-dystrophic lesions of the lumbosacral spine in case of HIP-SPINE-syndrome. It was presented the experience of surgical treatment of multilevel degenerative-dystrophic lesions of the lumbosacral spine in 52 patients aged from 48 to 81 years. Lumbar stenosis prevailed in 38 (73.1%) cases. There was degenerative spondylolisthesis in 9 (17.3%) cases, and degenerative scoliosis was detected in 5 (9.6%) patients. Different types of decompressive-stabilizing interventions according to direction of compression and the presence of degenerative instability were performed in all patients. Evaluation of surgical treatment was done by using of visual analog scale and questionnaire Oswestry Disability Index. It was revealed significant improvement of life quality by reducing of pain and increasing of daily activity. Maximal time of observation was 36 months.


Impaired vasopressin suppression and enhanced atrial natriuretic hormone release following an acute water load in primary aldosteronism.
The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) and their involvement in renal water and electrolyte metabolism in primary aldosteronism in humans were studied. An oral acute water load (20 ml/kg body weight) was given to each of 12 patients before and after surgical removal of their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured simultaneously, and renal water and electrolyte metabolism and tubular functions were determined. The same water load was given to seven normal subjects and the same parameters were determined. In the presence of mineralocorticoid excess before the operation, plasma AVP was relatively low compared with plasma osmolality (Posm), but was not suppressed in response to decreases in Posm after the water load. Baseline plasma ANH was high and increased further after the water load; urinary dilution and diuresis both remained normal. After the operation, baseline plasma AVP was normal and decreased in response to the decrease in Posm after the water load, with normal urinary dilution and diuresis. Baseline plasma ANH was normal, and did not increase after the water load. The ratio of urinary K and Na clearances and distal tubular reabsorption of Na increased before the operation. These results suggest that there are perturbations of AVP and ANH release in primary aldosteronism, despite the normal urinary dilution after a water load.


Primordial evolvability: Impasses and challenges.
While it is generally agreed that some kind of replicating non-living compounds were the precursors of life, there is much debate over their possible chemical nature. Metabolism-first approaches propose that mutually catalytic sets of simple organic molecules could be capable of self-replication and rudimentary chemical evolution. In particular, the graded autocatalysis replication domain (GARD) model, depicting assemblies of amphiphilic molecules, has received considerable interest. The system propagates compositional information across generations and is suggested to be a target of natural selection. However, evolutionary simulations indicate that the system lacks selectability (i.e. selection has negligible effect on the equilibrium concentrations). We elaborate on the lessons learnt from the example of the GARD model and, more widely, on the issue of evolvability, and discuss the implications for similar metabolism-first scenarios. We found that simple incorporation-type chemistry based on non-covalent bonds, as assumed in GARD, is unlikely to result in alternative autocatalytic cycles when catalytic interactions are randomly distributed. An even more serious problem stems from the lognormal distribution of catalytic factors, causing inherent kinetic instability of such loops, due to the dominance of efficiently catalyzed components that fail to return catalytic aid. Accordingly, the dynamics of the GARD model is dominated by strongly catalytic, but not auto-catalytic, molecules. Without effective autocatalysis, stable hereditary propagation is not possible. Many repetitions and different scaling of the model come to no rescue. Despite all attempts to show the contrary, the GARD model is not evolvable, in contrast to reflexively autocatalytic networks, complemented by rare uncatalyzed reactions and compartmentation. The latter networks, resting on the creation and breakage of chemical bonds, can generate novel ('mutant') autocatalytic loops from a given set of environmentally available compounds. Real chemical reactions that make or break covalent bonds, rather than mere incorporation of components, are necessary for open-ended evolvability. The issue of whether or not several concrete chemical systems (rather than singular curiosities) could realize reflexively autocatalytic macromolecular networks will ultimately determine the relevance of metabolism-first approaches to the origin of life, as stepping stones towards true open-endedness that requires the combination of rich combinatorial chemistry controlled by information stored in template replicators.


Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein.
Generation of active procoagulant cofactor factor Va (FVa) and its subsequent association with the enzyme activated factor X (FXa) to form the prothrombinase complex is a pivotal initial event in blood coagulation and has been the subject of investigative effort, speculation, and controversy. The current paradigm assumes that FV activation is initiated by limited proteolysis by traces of (meizo) thrombin. Recombinant tick salivary protein TIX-5 was produced and anticoagulant properties were studied with the use of plasma, whole blood, and purified systems. Here, we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B domain of FV and show that FXa activation of FV is pivotal for plasma and blood clotting. Accordingly, tick feeding is impaired on TIX-5 immune rabbits, displaying the in vivo importance of TIX-5. Our data elucidate a unique molecular mechanism by which ticks inhibit the host's coagulation system. From our data, we propose a revised blood coagulation scheme in which direct FXa-mediated FV activation occurs in the initiation phase during which thrombin-mediated FV activation is restrained by fibrinogen and inhibitors.


Exploration of irradiation intensity dependent external in-band quantum yield for ZnO and CuO/ZnO photocatalysts.
Decorating metal oxides with wide band-gap semiconductor nano-particles constitute an important approach for synthesizing nano-photocatalysts, where the photocatalytic activity is attributed to the band diagram related effective charge separation and external in-band quantum yield (EIQY). However, up to now, the correlation between the irradiation intensity and the functionalization of the in-band quantum yield has not yet been explained. In this work, by investigating the photocatalytic activity of ZnO and CuO/ZnO (CZO) nano-photocatalysts under various irradiative intensities, we show that the effective charge separation in the CuO/ZnO band alignment is sensitive to weak illumination, while ZnO exhibits a competitive photocatalytic activity with CZO under strong illumination. As a consequence, by modifying the irradiation intensity, the intrinsic ZnO can achieve a similar photocatalytic activity to that of metal oxide decorated ZnO. Besides, the optimal photocatalytic activity of CZO is found to be reachable by manipulating the pollutant concentration.


Color Constancy by Reweighting Image Feature Maps.
In this study, a novel illuminant color estimation framework is proposed for computational color constancy, which incorporates the high representational capacity of deep-learningbased models and the great interpretability of assumptionbased models. The well-designed building block, feature map reweight unit (ReWU), helps to achieve comparative accuracy on benchmark datasets with respect to prior state-of-the-art deep learning based models while requiring more compact model size and cheaper computational cost. In addition to local color estimation, a confidence estimation branch is also included such that the model is able to simultaneously produce point estimate and its uncertainty estimate, which provides useful clues for local estimates aggregation and multiple illumination estimation. The source code and the dataset have been made available1.


Surgical "Safe Zone": Rapid Anatomical Identification of the Lesser Occipital Nerve.
Surgical intervention has established a vital role in the management of chronic headaches. The lesser occipital nerve (LON) is a common target in patients suffering from occipital neuralgia and is often resected as a first-line option. We endeavored to define the relationships of the LON in the posterolateral neck to facilitate its safe and rapid intraoperative identification. Seven fresh cadavers (14 nerves) were dissected, and their relationships to the mastoid prominence and nearby spinal accessory nerve (SAN) and greater auricular nerve were noted. The distance from the mastoid to the emergence of the LON along the posterior sternocleidomastoid ranged from 36 to 51 mm (mean: 45.2 mm), with relative symmetry between the two nerves in the same cadaver. The SAN emerged an average of 54 mm from the mastoid prominence. Exploration for the LON should begin at a point 40 mm from the mastoid prominence along the posterior border of the sternocleidomastoid muscle. If the point of exit of the LON is not identified within 10 mm of this exposure, our dissection continues cranially along the posterior border of the sternocleidomastoid, anterior to the trapezius. In rare cases the nerve may pierce the fibers of the muscle and ascend directly on top of the muscle belly. By limiting the caudal extend of the dissection, we can avoid exposure of the SAN and minimize the risk of iatrogenic nerve injury.


Retinoblastoma: from disease to discovery.
Retinoblastoma has contributed much to the understanding of cancer. It provided the classic 'two-hit model' for oncogenesis and helped to identify the first tumor suppressor gene RB1. Thirty years since then, the search for additional events underlying disease progression continues. Phenotypic variations in retinoblastoma offer numerous clues to disease pathogenesis. Understanding their molecular biological basis will provide insight into mechanisms underlying tumor progression. These not fully understood genetic and stochastic events play a major role in uncontrolled retinal precursor cell proliferation. Comparative genomic hybridization and gene expression studies have facilitated probing of genes controlling basic events in cellular development, i.e. proliferation, differentiation and apoptosis. Research to determine the cell of origin that underlies the evolution of retinoblastoma can lead to understanding of the stochastic events underlying the genesis of this cancer, which currently remains unclear. In this review, we discuss the recent developments in retinoblastoma and describe how they are beginning to shape a new and revised picture of retinoblastoma pathogenesis and progression.


Diagnostic value of interactions between members of the family Neisseriaceae and lectins.
The lectin slide agglutination test for Neisseria gonorrhoeae has been modified and improved. Results show that wheat germ agglutinin and soybean lectin agglutinate 100% (193 of 193 tested) of clinical isolates of N. gonorrhoeae. Lectin-reactive meningococci can be readily identified by the hydrolysis of gamma-glutamyl-beta-naphthylamide. Branhamella catarrhalis, Neisseria lactamica, Neisseria sicca, Neisseria subflava, Neisseria perflava, and meningococcal serogroups A, B, C, X, Y, and Z do not interfere with the positive identification of N. gonorrhoeae. The frequently encountered problem of autoagglutination of members of the family Neisseriaceae may be circumvented by a short treatment of cellular suspensions with DNase. Based on agglutination assays, the enzyme treatment did not result in a loss of wheat germ agglutinin receptors from the bacteria. The lectin agglutination test, coupled with the gamma-glutamyl aminopeptidase assay, is proposed as a rapid and accurate means of identifying clinical isolates of gonococci.


In vivo PET imaging in rat of dopamine terminals reveals functional neural transplants.
Positron emission tomography (PET) and carbon-11-labeled 2B-carbomethoxy-3B-(4-fluorophenyl)tropane (11C-CFT or 11-WIN 35,428) were used as molecular markers for striatal presynaptic dopamine (DA) transporters in a unilateral Parkinson's disease rat neurotransplantation model. In the lesioned striatum, the binding ratio measured by the DA presynaptic marker was reduced to 15% to 35% of the intact side (or unoperated control). After grafting with non-DA cells (from dorsal mesencephalon), the DA binding ratio remained reduced to levels observed before transplantation and rats showed no behavioral recovery. In contrast, after DA neuronal transplantation, behavioral recovery occurred only after the 11C-CFT binding ratio had increased to 75% to 85% of the intact side. This study provides direct in vivo evidence for the dopaminergic molecular basis of functional recovery in the lesioned nigrostriatal system after neural transplantation.


Zinc-sensitive genes as potential new target genes of the metal transcription factor-1 (MTF-1).
Zinc is an essential trace element that serves as a structural constituent of a large number of transcription factors, which explains its pivotal role in the control of gene expression. Previous studies investigating the effect of zinc deficiency and zinc supplementation on gene expression in the human adenocarcinoma cell line HT-29 led to the identification of a considerable number of genes responding to alterations in cellular zinc status with changes in steady state mRNA levels. For 9 of 20 genes from these previous screenings that were studied in more detail, mRNA steady state levels responded to both high and low media zinc concentrations. As they are primarily zinc-dependent, we assessed whether these genes are controlled by the zinc-finger metal transcription factor MTF-1. To test this hypothesis we generated a doxycyline-inducible Tet-On HT-29 cell line overexpressing MTF-1. Using this conditional expression system, we present evidence that Kruppel-like factor 4 (klf4), hepatitis A virus cellular receptor 1 (hhav), and complement factor B (cfbp) are 3 potential new target genes of MTF-1. To support this, we used in silico analysis to screen for metal-responsive elements (MREs) within promotors of zinc-sensitive genes. We conclude that zinc responsiveness of klf4, hhav, and cfbp in HT-29 cells is mediated at least in part by MTF-1.


National Ambulatory Medical Care Survey: 2001 summary.
This report describes ambulatory care visits made to physician offices in the United States. Statistics are presented on selected characteristics of the physician's practice, the patient, and the visit. Results highlighting new items on continuity of care are presented. They include whether the visit was the first or a followup for a problem, number of visits to this provider in the past 12 months for established patients, and whether other physicians shared care for the patient's problem. The report also highlights estimates of practice characteristics for office-based physicians. The data presented in this report were collected from the 2001 National Ambulatory Medical Care Survey (NAMCS). NAMCS is part of the ambulatory care component of the National Health Care Survey that measures health care utilization by various types of providers. NAMCS is a national probability sample survey of visits to office-based physicians in the United States. Sample data are weighted to produce annual national estimates. Selected trends from the 1992 and 1997 NAMCS are also presented. During 2001, an estimated 880.5 million visits were made to physician offices in the United States, an overall rate of 314.4 visits per 100 persons. From 1992 through 2001, the visit rate for persons 45 years of age and over increased by 17%, from 407.3 to 478.2 visits per 100 persons. The mean age of patients at each office visit has steadily increased from 1992 through 2001 as has the mean number of diagnoses rendered and the overall drug mention rate. The visit rate to physician offices in metropolitan statistical areas (MSAs) (338.3 visits per 100 persons) was significantly larger than the rate in non-MSAs (218.0 visits per 100 persons). Females had a higher visit rate compared with males, and white persons had a higher rate than black or African-American persons. Half of all office visits were to the patient's primary care physician (PCP). Of the visits to physicians other than the patient's PCP, about one-third (32.6 percent) were referrals. About 1 in 10 office visits were made by new patients (11.8 percent), down 20% since 1992. More than one physician shared the care for the patient's condition at about one-fifth of the office visits. Of all visits made to offices in 2001, 58.8 percent listed private insurance as the primary expected source of payment, followed by Medicare (21.8 percent) and Medicaid and/or State Children's Health Insurance Program (7.2 percent). For preventive care visits, the female visit rate was over 75% higher than the rate for males (67.1 versus 37.7 visits per 100 persons). Essential hypertension, arthropathies, acute upper respiratory infection, and diabetes mellitus were the leading illness-related primary diagnoses. There were an estimated 99.8 million injury-related visits in 2001, or 35.6 visits per 100 persons. Diagnostic and screening services were ordered or provided at 82.8 percent of visits, therapeutic and preventive services were ordered or provided at 41.4 percent of visits, and medications were prescribed or provided at 61.9 percent of visits. On average, 2.4 medications were ordered or provided at each office visit with any mention of a medication. The leading therapeutic class for drugs mentioned at office visits included cardiovascular-renal drugs (14.7 percent of mentions) and pain-relieving drugs (12.1 percent of mentions). A physician was seen at a majority of visits (95.8 percent), and a registered or licensed practical nurse was seen at 31.3 percent of visits. From 1992 through 2001, changes were observed in the leading diagnoses, therapeutic drug classes, and drug mentions. Physician estimates revealed that primary care physicians were twice as likely as specialists to make home visits during an average week of work; when they conducted them, they made twice as many (6 versus 2-3 visits per week) as specialists. Approximately 3 in 10 physicians reported not accepting new capitated, privately insured patients, whereas only 6.8 percent did not accept noncapitated, privately insured patients.


Combined ligand and structure based approaches for narrowing on the essential physicochemical characteristics for CDK4 inhibition.
In the absence of an experimentally determined 3D structure of CDK4 (Cyclin-Dependent Kinase 4), QSARs (Quantitative Structure Activity Relationship) have been explored to rationalize binding affinity in terms of physicochemical and structural parameters. Further, docking on a homology model of CDK4 validated the derived QSARs and predicted the binding mode of this series of inhibitors. Relevant parameters and leave-one-out (LOO) cross-validation (q (2)) as well as an external test set validation (r (2) pred) judged the statistical significance and predictive ability of the models. Docking enabled a better understanding of protein-ligand interaction and provided a mechanistic interpretation in terms of physicochemical characteristics. It identified a unique hydrogen bonding between the imidazole of His-95 and the pyridine nitrogen in the ligand. It rationalized the need for R 2 substituents to be bulky and polar, while the substituent at R 8 to be hydrophobic and comparatively less steric. It also explained why at R 6 a variety of substituents are tolerated and how the presence of methyl at R 5 enhances binding affinity.


exampletestr-An easy start to unit testing R packages.
In spite of the utility of unit tests, most R package developers do not write them. exampletestr makes it easier to start writing unit tests by creating shells/skeletons of unit tests based on the examples in the user's package documentation. When completed, these unit tests test whether said examples run correctly. By combining the functionality of exampletestr with that of covr, having ensured that their examples adequately demonstrate the features of their package, the developer can have much of the work of constructing a comprehensive set of unit tests done for them.


Acid-sensing ion channels in pain and disease.
Why do neurons sense extracellular acid? In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. Significant progress has been made in understanding the structure and function of ASICs at the molecular level. Studies aimed at clarifying their physiological importance have suggested roles for ASICs in pain, neurological and psychiatric disease. This Review highlights recent findings linking these channels to physiology and disease. In addition, it discusses some of the implications for therapy and points out questions that remain unanswered.


Mechanisms of calcium influx into hippocampal spines: heterogeneity among spines, coincidence detection by NMDA receptors, and optical quantal analysis.
Dendritic spines receive most excitatory inputs in the vertebrate brain, but their function is still poorly understood. Using two-photon calcium imaging of CA1 pyramidal neurons in rat hippocampal slices, we investigated the mechanisms by which calcium enters into individual spines in the stratum radiatum. We find three different pathways for calcium influx: high-threshold voltage-sensitive calcium channels, NMDA receptors, and an APV-resistant influx consistent with calcium-permeable AMPA or kainate receptors. These pathways vary among different populations of spines and are engaged under different stimulation conditions, with peak calcium concentrations reaching >10 microM. Furthermore, as a result of the biophysical properties of the NMDA receptor, the calcium dynamics of spines are exquisitely sensitive to the temporal coincidence of the input and output of the neuron. Our results confirm that individual spines are chemical compartments that can perform coincidence detection. Finally, we demonstrate that functional studies and optical quantal analysis of single, identified synapses is feasible in mammalian CNS neurons in brain slices.


Comparison of fracture resistance and fracture characterization of bilayered zirconia/fluorapatite and monolithic lithium disilicate all ceramic crowns.
To compare the fracture resistance between bilayered zirconia/ fluorapatite and monolithic lithium disilicate heat-pressed crowns and characterize the mode of fracture failure. Thirty crown samples were sequentially fitted on a mandibular right first molar metal replica of an ivory prepared molar tooth. The crown specimens were divided in three groups (A, B, and C; n = 10 for each group). Group A consisted of bilayered zirconia/fluorhapatite pressed-over crowns with standard design crown copings (0.7 mm uniform thickness), Group B of bilayered zirconia/fluorhapatite with anatomical design crown copings, and Group C of lithium disilicate monolithic crowns. The samples were then dynamically loaded under water for 100,000 cycles with a profile of 250 N maximum load at 1,000 N/s rate and 2.0 Hz frequency. Loading was performed with a steel ball (5 mm in diameter) coming into contact with the test crown, loading to maximum, holding for 0.2 s, unloading and lifting off 0.5 mm. The samples were then fractured under static loading, in order to determine the ultimate crown strength. Analysis of the recorded fracture load values was carried out with one-way analysis of variance (ANOVA) followed by Tukey tests. Fractured specimens were examined by stereomicroscopy and scanning electron microscopy. The fracture loads measured were (N, means and standard deviations): Group A: 561.87 (72.63), Group B: 1,014.16 (70.18) and Group C: 1,360.63 (77.95). All mean differences were statistically significant (P < 0.001). Catastrophic fractures occurred in Group C, whereas mainly veneer fractures were observed in Groups A and B. In the present study, the heat-pressed monolithic lithium-disilicate crowns showed more fracture resistance than zirconia/fluorapatite pressed-over crowns. Within the bilayered groups, the anatomical zirconia coping design presented increased ceramic fracture resistance.


A Comprehensive Review on Energy Harvesting Integration in IoT Systems from MAC Layer Perspective: Challenges and Opportunities.
The Internet of Things (IoT) is revolutionizing technology in a wide variety of areas, from smart healthcare to smart transportation. Due to the increasing trend in the number of IoT devices and their different levels of energy requirements, one of the significant concerns in IoT implementations is powering up the IoT devices with conventional limited lifetime batteries. One efficient solution to prolong the lifespan of these implementations is to integrate energy harvesting technologies into IoT systems. However, due to the characteristics of the energy harvesting technologies and the different energy requirements of the IoT systems, this integration is a challenging issue. Since Medium Access Control (MAC) layer operations are the most energy-consuming processes in wireless communications, they have undergone different modifications and enhancements in the literature to address this issue. Despite the essential role of the MAC layer to efficiently optimize the energy consumption in IoT systems, there is a gap in the literature to systematically understand the possible MAC layer improvements allowing energy harvesting integration. In this survey paper, we provide a unified framework for different wireless technologies to measure their energy consumption from a MAC operation-based perspective, returning the essential information to select the suitable energy harvesters for different communication technologies within IoT systems. Our analyses show that only 23% of the presented protocols in the literature fulfill Energy Neutral Operation (ENO) condition. Moreover, 48% of them are based on the hybrid approaches, which shows its capability to be adapted to energy harvesting. We expect this survey paper to lead researchers in academia and industry to understand the current state-of-the-art of energy harvesting MAC protocols for IoT and improve the early adoption of these protocols in IoT systems.


Neuronal activity in the second somatosensory cortex of monkeys (Macaca mulatta) during active touch of gratings.
1. In penetrations made into the upper bank of the lateral sulcus in two monkeys (Macaca mulatta), cells were isolated from the second somatosensory cortex (SII). During single-cell recordings, animals performed an active touch task in which they rubbed their fingertips over pairs of gratings differing in groove width and indicated which was the smoother surface. Hand motion and downward applied force were measured and recorded during these strokes. 2. In this survey, 151 penetrations provided observations on 352 cells that responded to passive stimulation of the digits or during performance of the active touch task. Consistent with previous reports, receptive fields (RFs) in SII were large, often multi-digit, and frequently included a portion or all of the hand and occasionally the arm. Modality was determined for 92 of 127 fully characterized cells, and included 70 cutaneous, 5 deep, 11 Pacinian corpuscle, and 6 joint cells. Characteristic of SII, modality could not be defined in 35 cells that were unresponsive to passive stimulation or whose responses varied widely over time. 3. Response properties of a subgroup of 79 cells in SII resembled those previously studied in the primary somatosensory cortex (SI) and ventroposterior lateral nucleus of the thalamus (VPL) using identical procedures. Correlation analysis revealed that 29 of these cells, like a portion of cells in SI, responded to changes in groove width independent of force or velocity. This selectivity could be considered a form of feature specificity. 4. In contrast to SI and VPL, transient responses to the fingertips contacting small elevated metal bars, which demarcated the beginning, middle, and end of strokes across the gratings, were seen in a majority of SII cells (109/127). During contact with bars, 89 cells displayed excitatory responses and 20 cells showed suppressed activity. Twelve cells, which responded to bars in isolation from gratings, provided a possible example of increased stimulus selectivity. 5. Passive stimulation failed to activate 16 cells that responded, in some cases differentially to gratings or force, during the task. Responses of nine other cells demonstrated task-dependent modulation in the form of response reduction or enhancement during selected portions of the stroke. In these same cells, response changes did not occur under comparable stimulus conditions in other portions of the stroke that differed only in behavioral context. These types of selective response modulations, not noted in our previous studies of VPL or SI, suggest that mechanisms regulating sensory inputs may affect SII.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of Single-Leg Squat Speed and Depth on Dynamic Postural Control Under Single-Task and Dual-Task Paradigms.
Although single-leg squats are a common dynamic balance clinical assessment, little is known about the relationship between parameters that influence squat movement and postural control performance. The objective of this study was to determine the relationships between squat parameters (speed and depth) and postural control under single task and dual task. A total of 30 healthy college students performed single-leg squats under single task and dual task with Stroop. Random-intercepts generalized linear mixed models determined the effect of squat parameters on center of pressure (CoP) parameters. For each 1-cm·s-1 increase in squat speed, sway range (mediolateral: β = -0.03; anteroposterior: β = -0.05) and area (β = -0.25) decreased, whereas sway speed (mediolateral: β = 0.05; anteroposterior: β = 0.29; total: β = 0.29) increased. For each 1-cm increase in squat depth, sway range (mediolateral: β = 0.05; anteroposterior: β = 0.20) and area (β = 0.72) increased, whereas sway speed (anteroposterior: β = -0.14; total: β = -0.14) decreased. Compared with single task, the association between total and anteroposterior sway speed and squat speed was stronger under dual task. Clinicians and researchers should consider monitoring squat speed and depth when assessing dynamic balance during single-leg squats, as these parameters influence postural control, especially under dual task.


Discovering cancer immunotherapy targets in vivo.
A key challenge facing the cancer immunology field is the discovery of the most suitable targets for therapeutic intervention. We recently reported a novel RNA-interference (RNAi)-based approach for systematic discovery of such targets in the tumor microenvironment in vivo utilizing pooled shRNA libraries as a screening tool. Here, we discuss applying this unbiased method to develop innovative cancer therapeutics.


Molecular Subtyping of Blastocystis from Diverse Animals in the United Arab Emirates.
The contribution of Blastocystis from non-human hosts to zoonotic transmission is only partly known. The objective of this study was to determine the distribution of Blastocystis genetic subtypes in different animal species in United Arab Emirates. A total of 114 stool samples were tested using PCR of the small subunit (SSU) rRNA gene and sequence analysis. Twenty-three Blastocystis-positive samples were identified. The following detection rates were observed: cattle, 22.7%; sheep, 63.6%; rabbits, 33.3%; rodents, 37.5%; reptiles, 21.2%. Four subtypes were identified in this study; ST4, ST10, ST14, and ST17; ST10 was isolated from sheep and cattle, corroborating previous data indicating that these are natural hosts for this subtype. Cases of mixed subtype colonization were also detected. Conspicuously, we found ST14 in rabbits. The discovery of ST17 in a squirrel indicates a novel host for this subtype. Furthermore, the discovery of ST4 in rodents suggests that these may serve as reservoir for human Blastocystis ST4 colonization. Six tortoises and one iguana were positive for Blastocystis. In conclusion, this is the first report of Blastocystis infection in various animals in the UAE. Apart from ST4, no potentially zoonotic subtypes were detected.


The REPAIR Project: Examining the Biological Impacts of Sub-Background Radiation Exposure within SNOLAB, a Deep Underground Laboratory.
Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation. SNOLAB, located in Sudbury, Ontario, Canada, is a unique facility for examining the effects of sub-background radiation exposure. Originally constructed for astroparticle physics research, the laboratory is located within an active nickel mine at a depth of over 2,000 m. The rock overburden provides shielding equivalent to 6,000 m of water, thereby almost completely eliminating cosmic radiation. Additional features of the facility help to reduce radiological contamination from the surrounding rock. We are currently establishing a biological research program within SNOLAB: Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR project). We hypothesize that natural background radiation is essential for life and maintains genomic stability, and that prolonged exposure to sub-background radiation environments will be detrimental to biological systems. Using a combination of whole organism and cell culture model systems, the effects of exposure to a sub-background environment will be examined on growth and development, as well as markers of genomic damage, DNA repair capacity and oxidative stress. The results of this research will provide further insight into the biological effects of low-dose radiation exposure as well as elucidate some of the processes that may drive evolution and selection in living systems. This Radiation Research focus issue contains reviews and original articles, which relate to the presence or absence of low-dose ionizing radiation exposure.


Detection of filaria-specific IgG4 antibodies and filarial DNA, for the screening of blood spots for Brugia timori.
The establishment of simple, sensitive and specific tools for the diagnosis of brugian lymphatic filariasis is a prerequisite for a successful intervention to control the disease. In the simple and rapid Brugia Rapid (BR) test, an immunochromatographic dipstick is used to detect IgG(4) antibodies that are reactive with a recombinant Brugia malayi antigen. When sera from 109 individuals with Brugia microfilaraemias (12 with B. malayi and 97 with B. timori) were investigated using the BR test, all were found positive. In contrast, all of the 150 sera from individuals with Onchocerca volvulus or Mansonella infections investigated were found negative in BR tests. Some unwelcome cross-reactions were observed, however, with sera from individuals infected with Wuchereria bancrofti (three of 12 test-positive) and Dirofilaria (one of nine test-positive). In an attempt to facilitate sample collection and detect any cross-reactions, the BR dipstick was used to screen blood spots, that had been allowed to dry on filter paper, for B. timori microfilariae, before the dipstick-positive samples were tested with a PCR-based assay. Of the 66 individuals so tested, 37 (56%) were found positive by the BR test used on dry blood spots and eight (22%) by the filtration of fresh blood samples. Only nine of the 37 dipstick-positive samples were found PCR-positive. The combined use of BR tests and PCR-based assays, for testing blood spots in areas where brugian filariasis is endemic, appears to be a promising method not only for post-treatment monitoring but also for the certification activities planned within the framework of the Global Programme to Eliminate Lymphatic Filariasis.


Evaluation of polyglycolic aicd sutures in colon anastomoses.
An experimental study was carried out in dogs to compare the healing characteristics of colon anastomoses constructed with silk and catgut, with those in which Dexon sutures of the same gauge were used. Anastomoses constructed with Dexon sutures showed minimal suture reaction on the serosal surfaces, and excellent healing strength as determined by bursting-pressure studies. Inspection of the mucosal surfaces in these anastomoses revealed flawless, smooth, healing suture lines. The flexibility of tissues at the anastomotic line was found to be good, and friability of tissue minimal.


Kinetic therapy in critically ill trauma patients.
To compare the incidence of pulmonary complications and hospital resource utilisation in patients treated with continuous rotation therapy versus manual turning in a traditional hospital bed. Prospective, randomised clinical trial. Surgical intensive care unit of a large, tertiary care, urban hospital. One-hundred-and-thirty-seven consecutive injured patients admitted to the Surgical Intensive Care Unit were prospectively randomised to receive either the Rotorest Kinetic Treatment Table or a traditional hospital bed. One hundred of these patients met the study criteria and are the basis of this report. The patients' medical records were reviewed in a prospective manner to determine the frequency and severity of pulmonary complications and resource utilisation in the two patient groups. There were no significant differences in the minimum, average, or maximum pO 2, pCO 2, PEEP, IMV rate, or pre-extubation blood gases during the first seven days of the study. Fewer cardiac output measurements, arterial blood gas measurements, chest X-rays, respiratory therapies, hours intubated, days in the ICU, days in the step-down unit, days in the hospital, and lower ICU charges, respiratory care charges, and total hospital charges were utilised in the patients treated with the kinetic bed. The incidence of pulmonary event complications and process complications was lower in the group of patients treated on the Rotorest bed.(ABSTRACT TRUNCATED AT 250 WORDS)


Second generation photodynamic agents: a review.
Over the last decade, laser treatment of neoplastic diseases has become routine. The ability of these light-induced therapies to effect positive results is increased with the utilization of photosensitizing dyes. The approval of Photofrin in Canada as a first generation photodynamic therapeutic agent for the treatment of some forms of bladder cancer is being followed by the development of other agents with improved properties. At this time a number of second generation photosensitizing dyes are under study in phase I/II clinical trials. A review of the status of these trials along with mechanistic aspects is reviewed in this article. In addition, a review of the status of lasers to be utilized for photodynamic therapy gives some indication of which instruments could be considered for this therapy in the future.


Treatment of mice with the Ah receptor agonist and human carcinogen dioxin results in altered numbers and function of hematopoietic stem cells.
The aryl hydrocarbon receptor (AhR) mediates the carcinogenicity of a family of environmental contaminants, the most potent being 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increased incidence of lymphoma and leukemia in humans is associated with TCDD exposure. Although AhR activation by TCDD has profound effects on the immune system, precise cellular and molecular mechanisms have yet to be determined. These studies tested the hypothesis that alteration of marrow populations following treatment of mice with TCDD is due to an effect on hematopoietic stem cells (HSCs). Treatment with TCDD resulted in an increased number and proliferation of bone marrow (BM) populations enriched for HSCs. There was a time-dependent decrease in B-lineage cells with a concomitant increase in myeloid populations. The decrease in the B-cell lineage colony-forming unit-preB progenitors along with a transient increase in myeloid progenitors were consistent with a skewing of lineage development from lymphoid to myeloid populations. However, HSCs from TCDD-treated mice exhibited diminished capacity to reconstitute and home to marrow of irradiated recipients. AhR messenger RNA was expressed in progenitor subsets but is downregulated during HSC proliferation. This result was consistent with the lack of response following the exposure of 5-fluorouracil-treated mice to TCDD. The direct exposure of cultured BM cells to TCDD inhibited the growth of immature hematopoietic progenitor cells, but not more mature lineage-restricted progenitors. Overall, these data are consistent with the hypothesis that TCDD, through AhR activation, alters the ability of HSCs to respond appropriately to signals within the marrow microenvironment.


The Use of Head-Worn Displays for Vital Sign Monitoring in Critical and Acute Care: Systematic Review.
Continuous monitoring of patient vital signs may improve patient outcomes. Head-worn displays (HWDs) can provide hands-free access to continuous vital sign information of patients in critical and acute care contexts and thus may reduce instances of unrecognized patient deterioration. The purpose of the study is to conduct a systematic review of the literature to evaluate clinical, surrogate, and process outcomes when clinicians use HWDs for continuous patient vital sign monitoring. The review was registered with PROSPERO (CRD42019119875) and followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A literature search was conducted for articles published between January 1995 and June 2020 using the following databases: PubMed, Embase, CINAHL, PsycINFO, and Web of Science. Overall, 2 reviewers independently screened titles and abstracts and then assessed the full text of the articles. Original research articles that evaluated the clinical, surrogate, or process outcomes of head-mounted displays for continuous vital sign monitoring in critical care or acute care contexts were included. Of the 214 records obtained, 15 (7%) articles met the predefined criteria and were included in this review. Of the 15 studies, 7 (47%) took place in a clinical context, whereas the remainder took place in a simulation environment. In 100% (7/7) of the studies that evaluated gaze behavior, changes were found in gaze direction with HWDs. Change detection improvements were found in 67% (2/3) of the studies evaluating changes in the participants' ability to detect changes in vital signs. Of the 10 studies assessing the ease of use of the HWD, most participants of 7 (70%) studies reported that the HWD was easy to use. In all 6 studies in which participants were asked if they would consider using the HWD in their practice, most participants responded positively, but they often suggested improvements on the HWD hardware or display design. Of the 7 studies conducted in clinical contexts, none reported any clinical outcomes. Although there is limited and sometimes conflicting evidence about the benefits of HWDs from certain surrogate and process outcomes, evidence for clinical outcomes is lacking. Recommendations are to employ user-centered design when developing HWDs, perform longitudinal studies, and seek clinical outcomes. PROSPERO International Prospective Register of Systematic Reviews CRD42019119875; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=119875.


Neutron doses in negative pion radiotherapy.
Absorbed neutron doses in regions outside the treatment volume from negative pion radiotherapy are presented, based on neutron spectral measurements for pions stopping in a tissue-equivalent target. A Monte Carlo neutron transport computer code was developed and used to calculate the absorbed dose as a function of the distance from the centre of the treatment volume. The Monte Carlo code, which is a modification of a neutron detector efficiency code, follows neutrons and gamma rays as they interact with either hydrogen or oxygen nuclei in a phantom. The code includes neutron elastic scattering on both hydrogen and oxygen as well as five inelastic nuclear reactions on oxygen. The recoil charged particles which provide the absorbed dose are considered until the neutron escapes the phantom or its kinetic energy falls below 1 ke V. Calculations of absorbed dose are compared with earlier dose calculations and measurements. Measurements of the neutron spectrum from a tissue-equivalent target indicate that the total kinetic energy carried away by neutrons is about 76 MeV, which is a significantly higher value than that used in earlier estimates of the neutron dose. The calculations presented here suggest that the neutron dose outside large treatment volumes may limit the use of negative pions for some therapeutic applications.


Derivation and characterisation of the human embryonic stem cell lines, NOTT1 and NOTT2.
The ability to maintain human embryonic stem cells (hESCs) during long-term culture and yet induce differentiation to multiple lineages potentially provides a novel approach to address various biomedical problems. Here, we describe derivation of hESC lines, NOTT1 and NOTT2, from human blastocysts graded as 3BC and 3CB, respectively. Both lines were successfully maintained as colonies by mechanical passaging on mouse embryonic feeder cells or as monolayers by trypsin-passaging in feeder-free conditions on Matrigel. Undifferentiated cells retained expression of pluripotency markers (OCT4, NANOG, SSEA-4, TRA-1-60 and TRA-1-81), a stable karyotype during long-term culture and could be transfected efficiently with plasmid DNA and short interfering RNA. Differentiation via formation of embryoid bodies resulted in expression of genes associated with early germ layers and terminal lineage specification. The electrophysiology of spontaneously beating NOTT1-derived cardiomyocytes was recorded and these cells were shown to be pharmacologically responsive. Histological examination of teratomas formed by in vivo differentiation of both lines in severe immunocompromised mice showed complex structures including cartilage or smooth muscle (mesoderm), luminal epithelium (endoderm) and neuroectoderm (ectoderm). These observations show that NOTT1 and NOTT2 display the accepted characteristics of hESC pluripotency.


Blunted feedback processing during risk-taking in adolescents with features of problematic Internet use.
While the conceptualization of problematic Internet use (PIU) as a "behavioral addiction" resembling substance-use disorders is debated, the neurobiological underpinnings of PIU remain understudied. This study examined whether adolescents displaying features of PIU (at-risk PIU; ARPIU) are more impulsive and exhibit blunted responding in the neural mechanisms underlying feedback processing and outcome evaluation during risk-taking. Event-related potentials (ERPs) elicited by positive (i.e. reward) and negative (i.e. loss) feedback were recorded during performance on a modified version of the Balloon Analogue Risk Task (BART) among ARPIU (n=39) and non-ARPIU subjects (n=27). Compared to non-ARPIU, ARPIU adolescents displayed higher levels of urgency and lack of perseverance on the UPPS Impulsive Behavior Scale. Although no between-group difference in BART performance was observed, ERPs demonstrated overall decreased sensitivity to feedback in ARPIU compared to non-ARPIU adolescents, as indexed by blunted feedback-related negativity (FRN) and P300 amplitudes to both negative and positive feedback. The present study provides evidence for feedback processing during risk-taking as a neural correlate of ARPIU. Given recent concerns regarding the growing prevalence of PIU as a health concern, future work should examine the extent to which feedback processing may represent a risk factor for PIU, a consequence of PIU, or possibly both.


Cardiodynamic state is associated with systemic inflammation and fatal acute-on-chronic liver failure.
Acute-on-chronic liver failure (ACLF) is characterized by high short-term mortality and systemic inflammation (SI). Recently, different cardiodynamic states were shown to independently predict outcomes in cirrhosis. The relationship between cardiodynamic states, SI, and portal hypertension and their impact on ACLF development remains unclear. The aim of this study was therefore to evaluate the interplay of cardiodynamic state and SI on fatal ACLF development in cirrhosis. At inclusion, hemodynamic measures including cardiac index (CI) and hepatic venous pressure gradient of 208 patients were measured. Patients were followed prospectively for fatal ACLF development (primary endpoint). SI was assessed by proinflammatory markers such as interleukins (ILs) 6 and 8 and soluble IL-33 receptor (sIL-33R). Patients were divided according to CI (<3.2; 3.2-4.2; >4.2 L/min/m2 ) in hypo- (n = 84), normo- (n = 69) and hyperdynamic group (n = 55). After a median follow-up of 3 years, the highest risk of fatal ACLF was seen in hyperdynamic (35%) and hypodynamic patients (25%) compared with normodynamic (14%) (P = .011). Hyperdynamic patients showed the highest rate of SI. The detectable level of IL-6 was an independent predictor of fatal ACLF development. Cirrhotic patients with hyperdynamic and hypodynamic circulation have a higher risk of fatal ACLF. Therefore, the cardiodynamic state is strongly associated with SI, which is an independent predictor of development of fatal ACLF.


Amazon heart: an exploration of the role of challenge events in personal growth after breast cancer.
High-profile events where in response to the experience of breast cancer women take on adventure activities to raise awareness and/or funds for breast cancer are increasing. These activities offer physical and psychological challenges within a peer support group setting. We investigated the experiences of 21 breast cancer survivors who participated in a 7-day breast cancer awareness motorcycle ride. Assessments included a qualitative pre/postinterview, solicited diary, pre-6-month follow-up survey. Measures included satisfaction with life, distress, happiness, global well being, meaning in life. Motivators were a desire for peer support, to promote breast cancer awareness, enjoyment, and personal growth. The ride incorporated physical and emotional challenge. A positive peer support experience led to feelings of inner peace, accomplishment, self-learning, a positive perspective, and improved social support. For a minority of women peer support or recreational expectations were not met resulting in negative feelings. No significant changes were observed over time in adjustment measures. Adventure events where women undertake emotional and physical challenge in an environment of group peer support provide opportunity for personal growth. In this context, peer support may provide the catalyst for the experience to become transformational and so is critical to generating positive outcomes. Realistic expectations of the ride are also influential.


No association or linkage between an intronic polymorphism of presenilin-1 and sporadic or late-onset familial Alzheimer disease.
Recent reports have shown an association between an intronic polymorphism of the presenilin-1 (PSEN1) gene and late-onset (age at onset > 65) familial and sporadic (no family history) Alzheimer disease (AD). The reported association was independent of the effect of the only previously identified gene associated with late-onset AD, APOE. Blood samples were obtained from members of 122 multiplex AD families, 42 unrelated cases of AD with positive family histories of dementia, 456 sporadic cases of AD, and 317 controls of similar ages at examination to the cases. These samples were genotyped for an intronic polymorphism of the PSEN1 gene, located 3' to exon 8, and the data analyzed for evidence of association or linkage. The samples were also genotyped for APOE and the data analyzed to see if the association or linkage changed when controlling for APOE genotype. There was no statistically significant increase (at alpha = .01) in allele 1 (199 bp) or genotype 1/1 in the sporadic AD cases, or in a random sample of one affected from each multiplex family, compared to controls. When examining the effect of the PSEN1 polymorphism while controlling for APOE genotype, APOE genotype was strongly associated with AD, but the PSEN1 polymorphism genotype was not. Model-trait dependent (lod score) and independent (Sim1BD) methods detected no evidence of linkage between PSEN1 and AD. In this independent dataset, the previously reported association between the intronic PSEN1 polymorphism and AD cannot be confirmed, and the conclusion that PSEN1 is a major susceptibility gene for late-onset AD is not supported.


A case of prostate stromal sarcoma involving the rectum.
Sarcomas and related proliferative lesions of the specialized stroma of the prostate are very rare and have been classified into prostate stromal sarcoma (PSS) and prostatic stromal tumor of uncertain malignant potential based on histology. We herein describe a case of PSS. A 40-year-old male presented at a hospital with urinary distention. Magnetic resonance imaging revealed a large prostate mass, and the diagnosis was prostate sarcoma of uncertain differentiation by ultrasound-guided needle biopsy. Total pelvic exenteration was performed and a pathological diagnosis of PSS was ultimately reached. Ten months later, there have been no signs of metastasis or recurrence.


Surgical treatment of symptomatic osteochondroma. A three- to eight-year follow-up study.
Our aim was to investigate the outcome of excision ofosteochondromas. Between 1994 and 1998, 92 symptomatic osteochondromas in 86 patients were excised. There were 40 women and 46 men with a mean age of 20 years (3 to 62). Of these, 56 had a solitary osteochondroma and 30 had multiple hereditary tumours. The presenting symptoms were pain (79.1%), swelling (23.3%), reduced range of movement (19.8%), cosmetic abnormalities (17.4%), and bursitis (12.8%). The most common site (37.6%) was around the knee. Four patients had major complications (4.7%) including one intra-operative fracture of the femoral neck and three nerve palsies which resolved after decompression. Six patients had minor complications. Overall, 93.4% of the preoperative symptoms resolved after excision of the tumours. Excision is a successful form of treatment for symptomatic osteochondromas with a low morbidity.


MicroRNA-212 participates in the development of prostate cancer by upregulating BMI1 via NF-κB pathway.
To investigate the role of microRNA-212 in prostate cancer (PCa) and its underlying mechanism. MicroRNA-212 expressions in 72 PCa tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). The relationship between microRNA-212 expression and clinical characteristics of PCa patients was analyzed. Target genes of microRNA-212 were predicted by TargetScan and verified by luciferase reporter gene assay. Proliferation, cell cycle, and apoptosis of PCa cells were detected after transfection with corresponding plasmids of microRNA-212 in PCa cells, respectively. The effect of microRNA-212 on BMI1 and NF-κB pathway was detected by Western blot. MicroRNA-212 was downregulated in PCa patients. The survival rate of PCa patients with lower expression of microRNA-212 was remarkably lower than those with a higher level. After overexpression of microRNA-212, we observed inhibited proliferation and arrested cell cycle of PCa cells. Increased apoptosis was found after PCa cells were transfected with microRNA-212 mimic. Luciferase reporter gene assay showed that microRNA-212 was bound to BMI1, which further promoted PCa development via NF-κB pathway. MicroRNA-212 was downregulated in PCa tissues, which could promote the PCa development by targeting BMI1 via NF-κB pathway.


Generation of mtDNA homoplasmic cloned lambs.
Generally in mammals, individual animals contain only maternally inherited mitochondrial DNA (mtDNA), as paternal (sperm)-derived mitochondria are usually eliminated during early development. Somatic cell nuclear transfer (SCNT) bypasses the normal routes of mtDNA inheritance and introduces not only a different nuclear genome into the recipient cytoplast (in general an enucleated oocyte) but also somatic mitochondria. Differences in mtDNA genotype between recipient oocytes and potential mtDNA heteroplasmy due to persistence and replication of somatic mtDNA means that offspring generated by SCNT are not true clones. However, more importantly, the consequences of the presence of somatic mtDNA, mtDNA heteroplasmy, or possible incompatibility between nuclear and mtDNA genotypes on subsequent development and function of the embryo, fetus and offspring are unknown. Following sexual reproduction, mitochondrial function requires the biparental control of maternally inherited mtDNA, whereas following SCNT incompatibility between the recipient cell mitochondrial and transplanted nuclear genomes, or mtDNA heteroplasmy, may result in energy imbalance and initiate the onset of mtDNA-type disease, or disruption of normal developmental events. To remove the potentially adverse effects of somatic mtDNA following SCNT we have previously produced embryos using donor cells depleted to residual levels of mtDNA (mtDNA). We now report that these cells support development to term and produced live lambs in which no donor somatic mtDNA was detected, the lambs being homoplasmic for recipient oocyte DNA.


Nontuberculous Mycobacteria Isolation from Clinical and Environmental Samples in Iran: Twenty Years of Surveillance.
Nontuberculous mycobacteria (NTM) are opportunistic pathogens that are widely distributed in the environment. There is a lack of data on species distribution of these organisms from Iran. This study consists of a review of NTM articles published in Iran between the years 1992 and 2014. In this review, 20 articles and 14 case reports were identified. Among the 20 articles, 13 (65%) studies focused on NTM isolates from clinical specimens, 6 (30%) studies examined NTM isolates from environmental samples, and one (5%) article included both clinical and environmental isolates. M. fortuitum (229/997; 23%) was recorded as the most prevalent and rapid growing mycobacteria (RGM) species in both clinical (28%) and environmental (19%) isolated samples (P < 0.05). Among slow growing mycobacteria (SGM), M. simiae (103/494; 21%) demonstrated a higher frequency in clinical samples whereas in environmental samples it was M. flavescens (44/503; 9%). These data represent information from 14 provinces out of 31 provinces of Iran. No information is available in current published data on clinical or environmental NTM from the remaining 17 provinces in Iran. These results emphasize the potential importance of NTM as well as the underestimation of NTM frequency in Iran. NTM is an important clinical problem associated with significant morbidity and mortality in Iran. Continued research is needed from both clinical and environmental sources to help clinicians and researchers better understand and address NTM treatment and prevention.


Measurement of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome and its clinical significance.
To investigate the changes of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome (SARS) and its clinical significance. Subgroups of blood T lymphocytes in 93 patients with SARS were detected by flow cytometer. The results detected in 64 normal subjects and 50 patients with AIDS served as controls. The numbers of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes all significantly decreased in acute phase of patients with SARS [(722 +/- 533)/microliter, (438 +/- 353)/microliter, (307 +/- 217)/microliter] compared with those in normal controls [(1527 +/- 470)/microliter, (787 +/- 257)/microliter, (633 +/- 280)/microliter, all P <0.01], which was different from what we observed in patients with AIDS who had decreased CD(4)(+) [(296 +/- 298)/microliter] but increased CD(8)(+) [(818 +/- 566)/microliter] counts. The counts of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes decreased more apparently in patients with severe SARS. All the five patients who died had CD(4)(+) counts less than 200/microliter. As the patients' condition improved, CD(3)(+), CD(4)(+), and CD(8)(+) counts gradually returned to normal ranges. The damage of cellular immunity is probably an important mechanism of pathogenesis of SARS.


Distance-based detection of paracetamol in microfluidic paper-based analytical devices for forensic application.
Whisky adulteration is a prevalent practice driven by the high cost of these beverages. Counterfeiters commonly dilute whisky with less expensive alcoholic beverages, water, food additives, drugs or pharmaceuticals. Paracetamol (PAR), an analgesic drug that mitigates hangovers and headaches, is commonly used to adulterate whisky. Currently, the primary method for quantifying PAR levels is high-performance liquid chromatography, but this technique is both time consuming and usually generates more residues. In this context, the utilization of miniaturized and portable analytical devices becomes imperative for conducting point-of-care/need analyses. These devices offer several advantages, including portability, user-friendliness, low cost, and minimal material wastage. This study proposes the selective distance-based PAR quantification on whisky samples using a paper-based microfluidic analytical device (μPAD). Colorimetric detection on paper-based platforms offers great benefits such as affordability, portability, and the ability to detect PAR without complicated instrumentation. The optimal detection conditions were achieved by introducing 5 μL of a mixture containing 7.5 mmol L-1 of Fe(III) and K3[Fe(CN)6] into the detection zone, along with 12 μL of whisky samples into the sample zone. The method exhibited linear behavior within the concentration range from 15 to 120 mg L-1, with a determination coefficient of 0.998. PAR was quantified in adulterated samples. The results obtained with the paper-based devices were compared with a referenced method, and no significant differences were observed at a confidence level of 95%. The μPAD allowed to determine ca. 1 drop of pharmaceutical medicine PAR of 200 mg mL-1 in 1 L of solution, demonstrating excellent sensitivity. This method offers cost-effective and rapid analysis, reducing the consumption of samples, reagents, and wastes. Consequently, it could be considered a viable and portable alternative for analyzing beverages at criminal scenes, customs, and police operations, thereby enhancing the field of forensics.


Probes for narcotic receptor-mediated phenomena. 25. Synthesis and evaluation of N-alkyl-substituted (alpha-piperazinylbenzyl)benzamides as novel, highly selective delta opioid receptor agonists.
A series of N-alkyl- and N,N-dialkyl-4-[alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl] benzyl]-benzamides were synthesized and evaluated for binding affinities at mu, delta, and kappa opioid receptor subtypes. Several compounds (2e,f,h,i,m) strongly bound to the delta receptor with IC50 values in the nanomolar range. On the other hand, the binding affinities of these compounds for the mu and kappa receptors were in the micromolar or greater range indicating excellent delta opioid receptor subtype selectivities. In this series, two important structure-activity relationships were found for the delta receptor binding affinity. First, the spatial orientation of the alpha-benzylic position influenced the affinities with the alpha R derivatives 2a-n generally showing more than 10-fold greater affinity than the alpha S derivatives 3a-n. Second, the binding affinities were strongly influenced by the number of alkyl substituents on the amide nitrogen. N-Monoalkylbenzamide derivatives 2b-d showed lower affinity than N,N-dialkylbenzamide derivatives 2e-n, and the N-unsubstituted benzamide derivative 2a had the lowest affinity for the delta receptor in the series. The dramatic effect of the amide group substitution pattern on the binding affinity for the delta receptor strongly suggests that the amide function is an important structural element in the interaction of this series of compounds at the delta receptor. Selective compounds in this series were examined for binding affinity in cloned human mu and delta receptors. The results obtained generally paralleled those from the rat brain binding assay. Compounds 2e,f with potent delta binding affinities and high delta selectivities were shown to be delta agonists with high selectivity by studies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Compound 2f was the most selective compound in the rat brain and GPI/MVD assays with 1755- and 958-fold delta vs mu selectivity, respectively.


WOMEN'S EDUCATION AND UTILIZATION OF MATERNAL HEALTH SERVICES IN AFRICA: A MULTI-COUNTRY AND SOCIOECONOMIC STATUS ANALYSIS.
There is an abundant literature on the relationship between women's education and maternal and child outcomes, including antenatal and postnatal care, onset of antenatal care and skilled birth attendance. However, few studies have adopted the 'equity' lens, despite increasing evidence that inequities between rich and poor are increasing although maternal and child mortality is declining. This study examined the differential effects of women's education within different socioeconomic strata in Africa. The most recent Demographic and Health Surveys (DHS) conducted in the Democratic Republic of the Congo, Egypt, Ghana, Nigeria and Zimbabwe were used. In each country, the original sample was stratified into three socioeconomic groups: poor, middle and rich. For each maternal health service utilization variable, the gross and net effects of women's education, controlling for age, parity, religion, marital status, health insurance, access to health facilities, partner's education and current place of residence, were estimated using logistic regression, taking into account the complex sampling design of the DHS. The findings revealed country-specific variations in maternal health service utilization, and for most indicators there was a clear gradient among socioeconomic strata: women living in better-off households exhibited greater access to, and utilization of, maternal health services. Multivariate analyses revealed that women's education had a positive association with type of antenatal care provider, timing and frequency of antenatal care visits, place of delivery and presence of a skilled birth attendant at delivery. Many other factors were found to be significantly associated with maternal health service utilization. For instance, parity had a negative and significant association with timing of first antenatal care visit. Likewise, partner's education was positively and statistically associated with timing of first antenatal care visit. It is argued that an over-generalization of the association between women's education and maternal health service utilization can be misleading. Efforts to improve maternal health service utilization in Africa must adopt an 'equity' approach, taking into account the specific needs of sub-populations.


[Problems of disinfection and decontamination in the biological protection and prevention of contagious diseases].
The problems of biological protection of the general population and military staff against biological hazard sources, primarily against biological terrorism and military threat underlie works on the design of new disinfectants having a universal spectrum of antimicrobial action and less ecological hazard than currently available ones. Elimination of biological hazard require effective chemical disinfectants that can completely inactivate microbes of unknown etiology as rapidly as possible and that cause the minimum damage to environmental objects. The disinfectant PFK of various modifications is evaluated in terms of the requirements of that ecological and chemical concept aimed at testing chemicals entering the environment.


Functional correlates of optic flow motion processing in Parkinson's disease.
The visual input created by the relative motion between an individual and the environment, also called optic flow, influences the sense of self-motion, postural orientation, veering of gait, and visuospatial cognition. An optic flow network comprising visual motion areas V6, V3A, and MT+, as well as visuo-vestibular areas including posterior insula vestibular cortex (PIVC) and cingulate sulcus visual area (CSv), has been described as uniquely selective for parsing egomotion depth cues in humans. Individuals with Parkinson's disease (PD) have known behavioral deficits in optic flow perception and visuospatial cognition compared to age- and education-matched control adults (MC). The present study used functional magnetic resonance imaging (fMRI) to investigate neural correlates related to impaired optic flow perception in PD. We conducted fMRI on 40 non-demented participants (23 PD and 17 MC) during passive viewing of simulated optic flow motion and random motion. We hypothesized that compared to the MC group, PD participants would show abnormal neural activity in regions comprising this optic flow network. MC participants showed robust activation across all regions in the optic flow network, consistent with studies in young adults, suggesting intact optic flow perception at the neural level in healthy aging. PD participants showed diminished activity compared to MC particularly within visual motion area MT+ and the visuo-vestibular region CSv. Further, activation in visuo-vestibular region CSv was associated with disease severity. These findings suggest that behavioral reports of impaired optic flow perception and visuospatial performance may be a result of impaired neural processing within visual motion and visuo-vestibular regions in PD.


Development and validation of a nomogram for predicting hemodynamic response to balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.
Balloon pulmonary angioplasty (BPA) can effectively alleviate pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Identifying predictors of unfavorable hemodynamic response to BPA is essential to guide clinical practice. Therefore, our objective was to construct and validate a nomogram to facilitate clinicians predicting hemodynamic response to BPA. Patients with CTEPH and underwent BPA from May 2018 to April 2022 were retrospectively collected. Favorable hemodynamic response to BPA was defined as a mean pulmonary arterial pressure ≤30 mmHg and/or a reduction in pulmonary vascular resistance ≥30 % at follow-up. A total of 155 patients were included. At baseline, patients with favorable hemodynamic response had significantly lower proportion of occlusive lesions (11.11 % vs. 26.32 %, P = 0.017), higher diffusing capacity of the lungs for carbon monoxide (63.77 % ± 14.10 % vs. 59.11 % ± 11.78 %, P = 0.039), and better cardiac morphology than counterparts. LASSO regression and random forest were used to construct prediction models respectively. The LASSO regression model demonstrated better predictive ability and accuracy than the random forest model, as evidenced by higher area under curve (0.745 vs. 0.740) and lower Brier score (0.192 vs. 0.195). A nomogram was constructed based on the LASSO regression model, consisting of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter, number of treated pulmonary vessels and proportion of occlusion lesions. High predictive ability of the LASSO model was preserved in validation (C index 0.744). The current study constructed a nomogram with high accuracy in predicting BPA hemodynamic outcome, which could facilitate decision-making in clinical practice.


alpha-Chloralose alters autonomic reflex function of the lower urinary tract.
The effects of alpha-chloralose on the micturition reflex were evaluated using an efficiently voiding decerebrate cat model. At laparotomy cannulas were introduced into the urethra and/or bladder for measurement of urethral perfusion pressure and/or bladder pressure during bladder filling and voiding. After establishment of efficient voiding in the anesthetic-free decerebrate cat, chloralose, 50 mg/kg iv, was administered. Parameters assessed before and after anesthetic included bladder pressure at peak of contraction (voiding pressure), intravesical pressure at onset of bladder contraction (threshold pressure), contraction amplitude, duration of bladder contraction, bladder volume at onset of bladder contraction (volume threshold), and residual bladder volume after voiding (postvoid residual). In addition to these parameters, preparations with intact bladder-urethra and with divided bladder-urethra were used to assess effects of chloralose on voiding efficiency and coordination between bladder and urethra, respectively. Chloralose significantly reduced voiding pressure, contraction amplitude, and voiding efficiency. Neither vehicle for the chloralose nor sympathetic denervation of the lower urinary tract affected these reductions. Chloralose had no effect on direct contraction of the bladder and urethra produced by intra-arterial acetylcholine (25-100 micrograms). Chloralose converted the synergic bladder and urethral responses during voiding to dyssynergic responses. Neuromuscular blockade with gallamine, 10 mg/kg iv, improved voiding efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)


Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study.
In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010-2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78-2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.