Maternal Height and Preterm Birth: A Study on 192,432 Swedish Women.
There is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women. This study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between women's heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories. Every cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (≤155 cm or ≤-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (≥179 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants. Among Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.


Influence of amniotic fluid volume on lecithin estimation in prediction of respiratory distress.
One hundred samples of amniotic fluid were obtained by amniocentesis from 82 patients at different stages of normal and abnormal pregnancies. The concentration of lecithin was estimated together with the volume of the amniotic fluid, using the dilution technique. Thus the total quantity of lecithin in any amniotic sac could be calculated. While confirming the findings of others that concentrations of lecithin below 3.5 mg/100 ml in the liquor immediately before delivery suggested that the baby was likely to develop respiratory distress syndrome, we found that in borderline cases the total amount of lecithin in the sac was of greater prognostic significance than the lecithin concentration.


β-Lactoglobulin Peptide Fragments Conjugated with Caffeic Acid Displaying Dual Activities for Tyrosinase Inhibition and Antioxidant Effect.
The regulation of tyrosinase activity and reactive oxygen species is of great importance for the prevention of dermatological disorders in the fields of medicine and cosmetics. Herein, we report a strategy based on solid-phase peptide chemistry for the synthesis of β-lactoglobulin peptide fragment/caffeic acid (CA) conjugates (CA-Peps) with dual activities of tyrosinase inhibition and antioxidation. The purity of the prepared conjugates, CA-MHIR, CA-HIRL, and CA-HIR, significantly increased to 99%, as acetonide-protected CA was employed in solid-phase coupling reactions on Rink amide resins. The tyrosinase inhibitory activities of all CA-Pep derivatives were higher than the activity of kojic acid, and CA-MHIR exhibited the highest tyrosinase inhibition activity (IC50 = 47.9 μM). Moreover, CA-Pep derivatives displayed significantly enhanced antioxidant activities in the peroxidation of linoleic acid as compared to the pristine peptide fragments. All CA-Pep derivatives showed no cytotoxicity against B16-F1 melanoma cells.


Isometric Exercise for the Cervical Extensors Can Help Restore Physiological Lordosis and Reduce Neck Pain: A Randomized Controlled Trial.
The aim of this study was to investigate whether isometric neck extension exercise restores physiological cervical lordosis and reduces pain. Sixty-five patients with loss of cervical lordosis were randomly assigned to exercise (27 women, 7 men; mean age, 32.82 ± 8.83 yrs) and control (26 women, 5 men; mean age, 33.48 ± 9.67 yrs) groups. Both groups received nonsteroidal anti-inflammatory drugs for 10 days. The exercise group received additional therapy as a home exercise program, which consisted of isometric neck extension for 3 mos. Neck pain severity and cervical lordosis were measured at baseline and at 3 mos after baseline. Compared with baseline levels, cervical lordosis angle was significantly improved in the exercise group (P < 0.001) but not in the control group (P = 0.371) at the end of 3 mos. Moreover, the exercise group was significantly superior to the control group considering the number of patients in whom cervical lordosis angle returned to physiological conditions (85.2% vs. 22.5%; P < 0.001). At the end of 3 mos, pain intensity was significantly reduced in both groups compared with baseline levels (for all, P < 0.001). Nevertheless, considering the change from baseline to month 3, the reduction in pain was about twice in the exercise group compared with the control group (P < 0.001). Isometric neck extension exercise improves cervical lordosis and pain.


Caudal vena cava progesterone and LH release patterns on Day 14 of gestation in primiparous sows.
The aim of the present study was to explore the relationship between systemic and local progesterone secretion and LH pulsatility during implantation in the pig. Differences in progesterone concentrations measured locally in the caudal vena cava and systemically in the jugular vein were studied in eight primiparous sows on Day 14 of pregnancy. LH pulsatility was analysed for its effects on the local progesterone-releasing pattern. Mean (±s.d.) progesterone concentrations in the vena cava (65.5±19.8ngmL-1) were approximately double basal concentrations (33.6±13.1ngmL-1). Basal concentrations of progesterone and LH were calculated as the average of the lowest six values. Basal caudal vena cava and mean jugular (27.6±1.5ngmL-1) progesterone concentrations did not differ significantly. Pre- and postprandial jugular progesterone concentrations were significantly different in the morning and afternoon (P=0.025 and 0.023). Mean LH ranged from 0.24 to 0.43ngmL-1 and was approximately double as high as basal LH in individual sows. In 60.8% of cases, LH pulses were followed by a progesterone pulse within 1h. In conclusion, the present study showed that corpus luteum function appears to respond to LH pulsatility on Day 14 of pregnancy. However, the response varies at the level of individual sows. In addition, systemic postprandial decreases in progesterone were confirmed on Day 14 of pregnancy.


Current treatment of oral candidiasis: A literature review.
Candidiasis or oral candidosis is one of the most common human opportunistic fungal infections of the oral cavity. This pathology has a wide variety of treatment which has been studied until these days. The present study offers a literature review on the treatment of oral candidiasis, with the purpose of establish which treatment is the most suitable in each case. Searching the 24 latest articles about treatment of candidiasis it concluded that the incidence depends on the type of the candidiasis and the virulence of the infection. Although nystatin and amphotericin b were the most drugs used locally, fluconazole oral suspension is proving to be a very effective drug in the treatment of oral candidiasis. Fluconazole was found to be the drug of choice as a systemic treatment of oral candidiasis. Due to its good antifungal properties, its high acceptance of the patient and its efficacy compared with other antifungal drugs. But this drug is not always effective, so we need to evaluate and distinguish others like itraconazole or ketoconazole, in that cases when Candida strains resist to fluconazole. Key words:Candidiasis, treatment, miconazole, fluconazole, nystatin.


[Soluble CD4 antigens in the cerebrospinal fluid as a marker of lymphocytic infiltration of the central nervous system].
Early diagnosis of the central nervous system (CNS) infections is a precondition of their successful treatment. However, the essential standard examination of the cerebrospinal fluid (CSF) is sometimes neither specific enough to define their basic nature, nor sufficient to differentiate them from processes of non-infectious origin. Supposing that the released surface molecules of activated immunocompetent cells could better define the character of inflammatory reaction, the levels of soluble CD4 antigens (sCD4) were determined with enzyme-immunosorbent test in the CSF of the patients with various CNS diseases. In contrast to cerebrovascular insults, toxic-metabolic, and other conditions in control group, detectable sCD4 concentrations in acute encephalitis (24 +/- 11 U/ml) were verified at the beginning of the disease, being also present in cytologically diagnosed normal CSF findings. They were significantly higher (p<0.05) compared to acute serous meningitis (13.5 +/- 8 U/ml), while in purulent meningitis they were measurable only after the disease progression--in correlation with the disturbed brain system function. The obtained results suggested the significance of CD4 antigen levels in CSF as a sensitive and specific marker of lymphocytic infiltration of the brain parenchyma, the measurement of which could contribute to early identification of the CNS infections, better understanding of their pathogenesis, and the assessment of the actual level of the destruction of neurons.


Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis.
To investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS). A total of 145 patients with sporadic ALS and 73 healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale-Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model. Compared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years, p = 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival (p = 0.002). Sensory cortex hyperexcitability predicts short survival in patients with ALS.


Effects of ear-canal static pressure on pure-tone thresholds and wideband acoustic immittance.
Wideband acoustic immittance (WAI) measures provide information about middle-ear function across the traditional audiometric frequency range from 0.25 to 8.0 kHz. Recent studies have found that WAI is effective in predicting the presence of conductive hearing loss (CHL). It is not known whether WAI can accurately estimate the degree of threshold shift caused by CHL. The purpose of the present study was to evaluate the relationship between changes in pure-tone threshold and changes in wideband absorbance and acoustic conductance levels induced by positive and negative ear-canal static pressure. Twenty young adult subjects with normal hearing and a negative history of middle-ear disorders participated in the study. Experimental pure-tone thresholds at 0.5 and 2.0 kHz were estimated by using a three-interval, three-alternative forced-choice adaptive psychometric procedure under three conditions: ambient ear-canal pressure, +200 daPa static pressure, and -200 daPa static pressure. Wideband absorbance and conductance were obtained in the same subjects by using a Welch Allyn prototype diagnostic middle ear analyzer. Changes in pure-tone threshold from the ambient pressure condition to the static pressure condition were evaluated by using a paired-samples t test and Pearson product-moment correlation. Wideband middle-ear absorbance and conductance at ambient pressure in this study were consistent with published data in adults with normal hearing. The mean change in threshold at 0.5 and 2.0 kHz with +200 daPa or -200 daPa ear-canal static pressure was similar to the mean change in absorbance and conductance levels in the same conditions. However, there was one statistically significant difference between the shift in pure-tone threshold and the change in conductance level for the +200 daPa pressure condition for 2.0 kHz, with the change in threshold being 1.5 dB greater than the change in conductance level (t = 2.39, p = 0.03). In contrast to the good performance of WAI measures in predicting mean threshold shifts caused by ear-canal pressure, the shifts in WAI were not correlated with threshold shifts. Thus WAI was not well suited to predict individual threshold changes caused by ear-canal static pressure. For the conditions of this study, results suggest that mean change in absorbance or conductance level caused by ear-canal static pressure of +200 daPa or -200 daPa provides a good estimate of the change in pure-tone threshold in the same conditions. However, individual threshold change was not accurately predicted by the change in absorbance or conductance level.


Survival analysis of irish amyotrophic lateral sclerosis patients diagnosed from 1995-2010.
The Irish ALS register is a valuable resource for examining survival factors in Irish ALS patients. Cox regression has become the default tool for survival analysis, but recently new classes of flexible parametric survival analysis tools known as Royston-Parmar models have become available. We employed Cox proportional hazards and Royston-Parmar flexible parametric modeling to examine factors affecting survival in Irish ALS patients. We further examined the effect of choice of timescale on Cox models and the proportional hazards assumption, and extended both Cox and Royston-Parmar models with time varying components. On comparison of models we chose a Royston-Parmar proportional hazards model without time varying covariates as the best fit. Using this model we confirmed the association of known survival markers in ALS including age at diagnosis (Hazard Ratio (HR) 1.34 per 10 year increase; 95% CI 1.26-1.42), diagnostic delay (HR 0.96 per 12 weeks delay; 95% CI 0.94-0.97), Definite ALS (HR 1.47 95% CI 1.17-1.84), bulbar onset disease (HR 1.58 95% CI 1.33-1.87), riluzole use (HR 0.72 95% CI 0.61-0.85) and attendance at an ALS clinic (HR 0.74 95% CI 0.64-0.86). Our analysis explored the strengths and weaknesses of Cox proportional hazard and Royston-Parmar flexible parametric methods. By including time varying components we were able to gain deeper understanding of the dataset. Variation in survival between time periods appears to be due to missing data in the first time period. The use of age as timescale to account for confounding by age resolved breaches of the proportional hazards assumption, but in doing so may have obscured deficiencies in the data. Our study demonstrates the need to test for, and fully explore, breaches of the Cox proportional hazards assumption. Royston-Parmar flexible parametric modeling proved a powerful method for achieving this.


The use of a simple home flow test as a quality indicator for male patients treated for lower urinary tract symptoms suggestive of bladder outlet obstruction.
To evaluate the performance of a simple home flow test (HFT) in the examination and follow-up of patients suffering from lower urinary tract symptoms suggestive of bladder outlet obstruction. One hundred seventy-two patients who were treated with either transurethral resection of the prostate or transurethral microwave therapy were included. Symptom evaluation, HFT and uroflowmetry were done before and 3 months following treatment. The patients' opinions about the need for further therapy and the effect of therapy were categorised at the follow-up. The HFT correlated strongly with the maximum flow rate (Qmax) both before and after therapy and it was better correlated to the symptoms of the patients and to the subjective effect of therapy compared to the Qmax. HFT is a cost-saving diagnostic technique for the classification of urinary flow and should be useful as a quality indicator in large-scale health care management programs.


Self-reported stress and subsequent hospital admissions as a result of hypertension, varicose veins and haemorrhoids.
This study examines a cohort in which individuals of privileged socio-economic position report greater psychological stress. We have previously shown in this cohort that stress is unrelated to coronary heart disease as measured by hospital discharge diagnosis and cause-specific death. In contrast, stress and hospitalization for cardiovascular conditions not requiring mandatory admission were associated. We hypothesized that psychosocial factors, in particular reporting tendency, are the likely mediator of this association, and the present study considers this further. A total of 5,596 men underwent a health screening during which they completed the Reeder Stress Inventory. Details of hospital admissions were retrieved from the Scottish Morbidity Records over a 21 year follow-up. Relationships between stress and admission were evaluated using proportional hazards regression. Compared with low stress, reported high stress was found to be associated with increased numbers of admissions for each of three most common cardiovascular causes of non-mandatory admission: adjusted hazard ratios were 3.43 for essential hypertension (95 per cent confidence interval (CI) 1.36-8.65), 1.91 for lower limb varicose veins (95 per cent CI 1.12-3.24), and 2.01 for haemorrhoids (95 per cent CI 1.16-3.51). Stress and blood pressure at baseline were not associated. The association between stress and admissions as a result of hypertension appears unlikely to be mediated by blood pressure. More likely is a mechanism based upon the reporting of symptoms, or the recording of discharge diagnoses. There is no obvious medical explanation for associations between stress and hospitalization as a result of varicose veins or haemorrhoids, and again it is likely that psychosocial factors provide the mechanism.


Regionalisation of rural medical training in far north Queensland: a learning experience for medical educators and managers.
The need for an appropriate, dedicated vertically-integrated training pathway for rural doctors, provided by regional consortia of educational organisations, has been clearly identified by Rural Doctors Association of Queensland (RDAQ) and The Australian College of Rural and Remote Medicine (ACRRM) as a key strategy to resolve rural medical workforce issues. The opportunity to put the ideas into action is now here with rural doctors responding to the challenge of managing more reform in general practice all over Australia. In Far North Queensland, the ongoing reform of general practice education has been challenging, with many lessons learned by both educators and managers. This paper describes the management of change, and outlines key principles and characteristics of a successful regional rural medical training system, building on the lessons learned from the Rural and Remote Area Placement Program (RRAP) and other projects.


Nitric oxide synthase inhibitors that interact with both heme propionate and tetrahydrobiopterin show high isoform selectivity.
Overproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of α-amino functionalized aminopyridine derivatives (3-8) were designed to probe the structure-activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a Ki of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors.


Timing of activities of daily life is jaggy: How episodic ultradian changes in body and brain temperature are integrated into this process.
Charles Darwin noted that natural selection applies even to the hourly organization of daily life. Indeed, in many species, the day is segmented into active periods when the animal searches for food, and inactive periods when the animal digests and rests. This episodic temporal patterning is conventionally referred to as ultradian (<24 hours) rhythmicity. The average time between ultradian events is approximately 1-2 hours, but the interval is highly variable. The ultradian pattern is stochastic, jaggy rather than smooth, so that although the next event is likely to occur within 1-2 hours, it is not possible to predict the precise timing. When models of circadian timing are applied to the ultradian temporal pattern, the underlying assumption of true periodicity (stationarity) has distorted the analyses, so that the ultradian pattern is frequently averaged away and ignored. Each active ultradian episode commences with an increase in hippocampal theta rhythm, indicating the switch of attention to the external environment. During each active episode, behavioral and physiological processes, including changes in body and brain temperature, occur in an integrated temporal order, confirming organization by programs endogenous to the central nervous system. We describe methods for analyzing episodic ultradian events, including the use of wavelet mathematics to determine their timing and amplitude, and the use of fractal-based procedures to determine their complexity.


Harm and benefits of primary liver resection and salvage transplantation for hepatocellular carcinoma.
Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm.


Frequent emergency department use in the paediatric population: A systematic literature review.
We systematically reviewed the literature on paediatric frequent emergency department (ED) users to identify and to synthesize characteristics and factors associated with frequent ED utilization among this population in the United States. We searched Medline (Ovid), CINAHL (Ebsco), and Embase (Ovid) to identify all relevant studies after 1990. We focused on US studies analysing paediatric frequent ED (PFED) users excluding those focused on specific subgroups. Two reviewers independently selected articles and extracted data on predisposing, enabling, behavioural, need and reinforcing factors. Fifteen studies met the inclusion criteria. PFED users comprised 3% to 14% of all paediatric ED users and accounted for 9% to 42% of all paediatric ED visits in 11 studies that defined frequent use as four to six ED visits per year. Most PFED users were less than 5 years old who had public insurance coverage and a regular provider. Public insurance compared to private residency in disadvantaged areas, having at least one chronic or complex condition and a history of hospitalization, were associated with frequent use. Children who had a regular primary care provider were less likely to exhibit frequent ED use. Minimizing unnecessary ED visits by frequent utilizers is a quality improvement and cost-saving priority for health systems. Our findings indicate that many PFED users have greater healthcare needs and face barriers accessing care in a timely manner, even though some have regular providers. To better address the needs of this vulnerable group, health systems should focus on educating caregivers and expanding access to providers in other settings.


Multiplex PCB-based electrochemical detection of cancer biomarkers using MLPA-barcode approach.
Asymmetric multiplex ligation-dependent probe amplification (MLPA) was developed for the amplification of seven breast cancer related mRNA markers and the MLPA products were electrochemically detected via hybridization. Seven breast cancer genetic markers were amplified by means of the MLPA reaction, which allows for multiplex amplification of multiple targets with a single primer pair. Novel synthetic MLPA probes were designed to include a unique barcode sequence in each amplified gene. Capture probes complementary to each of the barcode sequences were immobilized on each electrode of a low-cost electrode microarray manufactured on standard printed circuit board (PCB) substrates. The functionalised electrodes were exposed to the single-stranded MLPA products and following hybridization, a horseradish peroxidase (HRP)-labelled DNA secondary probe complementary to the amplified strand completed the genocomplex, which was electrochemically detected following substrate addition. The electrode arrays fabricated using PCB technology exhibited an excellent electrochemical performance, equivalent to planar photolithographically-fabricated gold electrodes, but at a vastly reduced cost (>50 times lower per array). The optimised system was demonstrated to be highly specific with negligible cross-reactivity allowing the simultaneous detection of the seven mRNA markers, with limits of detections as low as 25pM. This approach provides a novel strategy for the genetic profiling of tumour cells via integrated "amplification-to-detection".


Identification of novel non-coding RNAs using profiles of short sequence reads from next generation sequencing data.
The increasing interest in small non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs) and recent advances in sequencing technology have yielded large numbers of short (18-32 nt) RNA sequences from different organisms, some of which are derived from small nucleolar RNAs (snoRNAs) and transfer RNAs (tRNAs). We observed that these short ncRNAs frequently cover the entire length of annotated snoRNAs or tRNAs, which suggests that other loci specifying similar ncRNAs can be identified by clusters of short RNA sequences. We combined publicly available datasets of tens of millions of short RNA sequence tags from Drosophila melanogaster, and mapped them to the Drosophila genome. Approximately 6 million perfectly mapping sequence tags were then assembled into 521,302 tag-contigs (TCs) based on tag overlap. Most transposon-derived sequences, exons and annotated miRNAs, tRNAs and snoRNAs are detected by TCs, which show distinct patterns of length and tag-depth for different categories. The typical length and tag-depth of snoRNA-derived TCs was used to predict 7 previously unrecognized box H/ACA and 26 box C/D snoRNA candidates. We also identified one snRNA candidate and 86 loci with a high number of tags that are yet to be annotated, 7 of which have a particular 18mer motif and are located in introns of genes involved in development. A subset of new snoRNA candidates and putative ncRNA candidates was verified by Northern blot. In this study, we have introduced a new approach to identify new members of known classes of ncRNAs based on the features of TCs corresponding to known ncRNAs. A large number of the identified TCs are yet to be examined experimentally suggesting that many more novel ncRNAs remain to be discovered.


Glucagon-like peptide-2 receptor modulates islet adaptation to metabolic stress in the ob/ob mouse.
Glucagon-like peptide-2 (GLP-2) is a gut hormone that increases gut growth, reduces mucosal cell death, and augments mesenteric blood flow and nutrient absorption. Exogenous GLP-2(1-33) also stimulates glucagon secretion and enhances gut barrier function with implications for susceptibility to systemic inflammation and subsequent metabolic dysregulation. We examined the importance of GLP-2 receptor (GLP-2R) signaling for glucose homeostasis in multiple models of metabolic stress, diabetes, and obesity. Body weight, islet function, glucose tolerance, and islet histology were studied in wild-type, high-fat fed, lean diabetic, Glp2r(-/-) and ob/ob:Glp2r(-/-) mice. GLP-2 did not stimulate glucagon secretion from isolated pancreatic islets in vitro, and exogenous GLP-2 had no effect on the glucagon response to insulin-induced hypoglycemia in vivo. Glp2r(-/-) mice exhibit no change in glycemia, and plasma glucagon levels were similar in Glp2r(-/-) and Glp2r(+/+) mice after hypoglycemia or after oral or intraperitoneal glucose challenge. Moreover, glucose homeostasis was comparable in Glp2r(-/-) and Glp2r(+/+) mice fed a high-fat diet for 5 months or after induction of streptozotocin-induced diabetes. In contrast, loss of the GLP-2R leads to increased glucagon secretion and alpha-cell mass, impaired intraperitoneal glucose tolerance and hyperglycemia, reduced beta-cell mass, and decreased islet proliferation in ob/ob:Glp2r(-/-) mice. Our results show that, although the GLP-2R is not critical for the stimulation or suppression of glucagon secretion or glucose homeostasis in normal or lean diabetic mice, elimination of GLP-2R signaling in obese mice impairs the normal islet adaptive response required to maintain glucose homeostasis.


Effects of CYP2C8 and SLCO1B1 Genetic Polymorphisms on Repaglinide Pharmacokinetics: A Systematic Review and Meta-Analysis.
The purpose of this systematic review and meta-analysis was to summarize the potential impact of CYP2C8 and SLCO1B1 genetic polymorphisms on repaglinide pharmacokinetics. A systematic search was conducted using electronic databases. Eligible studies reported data from pharmacokinetic evaluations of repaglinide in healthy adults according to different categories of CYP2C8 and SLCO1B1 genetic polymorphisms. Six studies including a total of 191 participants met the inclusion criteria. We noted that CYP2C8 *1/*3 carriers exhibited lower AUC(0-∞) (SMD: -0.77; 95%CI: -1.23 to -0.30; P=0.001) and Cmax (SMD: -0.94; 95%CI: - 1.41 to -0.47; P<0.001) than CYP2C8 *1/*1 carriers. There were no significant differences in AUC(0-∞), Cmax, t1/2 and mean change in blood glucose concentration between *1/*4 and *1/*1 carriers. Further, *3/*3 carriers had lower Cmax (SMD: -1.42; 95%CI: -2.66 to -0.17; P=0.026) than *1/*1 carriers. Additionally, *3/*3 carriers had lower Cmax than *1/*3 carriers (SMD: -1.20; 95%CI: -2.40 to -0.00; P=0.050). Finally, we noted that repaglinide pharmacokinetics did not differ by SLCO1B1 genotype. The current systematic review and meta-analysis indicated that the genotype of CYP2C8, but not SLCO1B1, may affect repaglinide pharmacokinetics. However, because of the comparatively insufficient number of published studies included, our conclusions require support from additional studies.


Tactile spatial resolution in blind braille readers.
To determine if blind people have heightened tactile spatial acuity. Recently, studies using magnetic source imaging and somatosensory evoked potentials have shown that the cortical representation of the reading fingers of blind Braille readers is expanded compared to that of fingers of sighted subjects. Furthermore, the visual cortex is activated during certain tactile tasks in blind subjects but not sighted subjects. The authors hypothesized that the expanded cortical representation of fingers used in Braille reading may reflect an enhanced fidelity in the neural transmission of spatial details of a stimulus. If so, the quantitative limit of spatial acuity would be superior in blind people. The authors employed a grating orientation discrimination task in which threshold performance is accounted for by the spatial resolution limits of the neural image evoked by a stimulus. The authors quantified the psychophysical limits of spatial acuity at the middle and index fingers of 15 blind Braille readers and 15 sighted control subjects. The mean grating orientation threshold was significantly (p = 0.03) lower in the blind group (1.04 mm) compared to the sighted group (1.46 mm). The self-reported dominant reading finger in blind subjects had a mean grating orientation threshold of 0.80 mm, which was significantly better than other fingers tested. Thresholds at non-Braille reading fingers in blind subjects averaged 1.12 mm, which were also superior to sighted subjects' performances. Superior tactile spatial acuity in blind Braille readers may represent an adaptive, behavioral correlate of cortical plasticity.


Monitoring flow in extracranial-intracranial bypass grafts using duplex ultrasonography: a single-center experience in 80 grafts over 8 years.
High-flow extracranial-intracranial (EC-IC) bypass is performed by using radial artery graphs (RAGs) or saphenous vein grafts (SVGs) for various pathologies such as aneurysms, ischemia, and skull-base tumors. Quantifying the acceptable amount of blood flow to maintain proper cerebral perfusion has not been well established, nor have the variables that influence flow been determined. To identify the normative range of blood flow through extracranial-intracranial RAGs and SVGs as measured by duplex ultrasonography. Multiple variables were evaluated to better understand their influence of graft flow. All EC-IC grafts performed at Harborview Medical Center from 2005 to 2012 were retrospectively reviewed for this cohort study. Daily extracranial graft duplex ultrasonography with flow volumes and transcranial graft Doppler were examined, as were short- and long-term outcomes. Both ischemic and hyperemic events were evaluated in further detail. Eighty monitorable high-flow EC-IC bypasses were performed over the 8-year period. Sixty-five bypasses were performed by using RAGs and 15 were performed with SVGs. The average flow was 133 mL/min for RAGs and 160 mL/min for SVGs (P = .25). For both RAG and SVG groups, the donor and recipient vessel selected significantly impacted flow. For the RAG group only, preoperative graft diameter, postoperative hematocrit, and postoperative date significantly influenced flow. A 1-week average of >200 mL/min was 100% sensitive to cerebral hyperemia syndrome. This study establishes the normative range of duplex ultrasonographic flow after high-flow EC-IC bypass, as well the usefulness and practicality of such monitoring as a surrogate to flow in the postoperative period.


Trauma care systems in Saudi Arabia: an agenda for action.
Saudi Arabia is undergoing a rapid population growth that along with improved socioeconomics has led many individuals to own a car or even a number of cars per family, resulting in a greater number of vehicles on the roads. The reduced focus on good public transportation systems and the dependence on cars for transportation have created a diversity of drivers who are unfamiliar with the local driving rules and lack the basic skills for safe driving. This is in addition to some young drivers who frequently violate traffic laws and tend to speed most of the time. This unplanned expansion in road traffic has resulted in more car accidents, injuries, disabilities, and deaths. Accompanying that is an increased socioeconomic burden, depletion of human resources, emotional and psychological stress on families, and a strain on healthcare facilities. If this continues without prompt intervention, it will lead to increased insurance premiums and may become unmanageable. To minimize this impact, a national or regional multidisciplinary trauma system has to be developed and implemented. A trauma system is a preplanned, comprehensive, and coordinated regional injury response network that includes all facilities with the capability to care for the injured. Essential components of the system include trauma prevention, prehospital care, hospital care, rehabilitation, system administration, trauma care education and training, trauma care evaluation and quality improvement, along with the participation of society. Research has documented a significant decrease in morbidity and mortality from trauma after the implementation of such systems, depending on their efficiency. The purpose of this review is to discuss the problem of road traffic accidents in this country and address the trauma care system as an effective solution.


Skin anti-aging strategies.
Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall "well-being" and the perception of "health" in humans, several anti-aging strategies have been developed during the last years. It is the intention of this article to review the most important anti-aging strategies that dermatologists have nowadays in hand, including including preventive measurements, cosmetological strategies, topical and systemic therapeutic agents and invasive procedures.


Pulmonary hypertension in advanced chronic obstructive pulmonary disease.
Pulmonary hypertension is a common complication seen in patients with advanced chronic obstructive pulmonary disease (COPD). Information related to the true prevalence, implications for functional outcomes, pathogenesis, and therapeutic options available has been lacking. The purpose of this review is to summarize some exciting findings from the last several years that address these holes in our knowledge. Several recent studies have explored the prevalence and the functional implications of pulmonary hypertension for patients with COPD. These highlight the importance of clearly defining pulmonary hypertension that can be quite heterogeneous in this patient population. Furthermore, the concept that pulmonary hypertension in COPD is merely driven by hypoxic vasoconstriction has been called into question by several lines of investigation that suggest a much more complex pathogenesis potentially occurring independently of hypoxemia. Finally, there has been much interest in exploring pulmonary hypertension-specific therapies in patients with COPD, but available data to support their use are limited. The recent findings summarized here have expanded our knowledge regarding this important comorbidity in patients with advanced COPD. We now know that pulmonary hypertension is common, has clear effects on both morbidity and mortality, and has a complex pathophysiology that we are only beginning to understand.


Cyclometalated (N,C) Au(III) Complexes: The Impact of Trans Effects on Their Synthesis, Structure, and Reactivity.
ConspectusThe early years of gold catalysis were dominated by Au(I) complexes and inorganic Au(III) salts. Thanks to the development of chelating ligands, more sophisticated Au(III) complexes can now be easily prepared and handled. The choice of the ancillary ligand has great consequences for the synthesis, properties, and reactivity of the Au(III) complex in question. Among the major factors controlling reactivity are the "trans effect" and the "trans influence" that a ligand imparts at the ligand trans to itself. The kinetic trans effect manifests itself with an increased labilization of the ligand trans to a given ligand and arises from an interplay between ground-state and transition-state effects. The term trans influence, on the other hand, is a ground-state effect only, describing the tendency of a given ligand to weaken the metal-ligand bond trans to itself. Herein, we will use the term "trans effect" to describe both the kinetic and the thermodynamic properties, whereas the term "trans influence" will refer only to thermodynamic properties. We will describe how these trans effects strongly impact the chemistry of the commonly encountered cyclometalated (N,C) Au(III) complexes, a class of complexes we have studied for more than a decade. We found that the outcome of reactions like alkylation, arylation, and alkynylation as well as halide metathesis are dictated by the different trans influence of the two termini of the chelating tpy ligand in (tpy)Au(OAcF)2 (tpy = 2-(p-tolyl)pyridine, OAcF = OCOCF3, tpy-C > tpy-N). There is a strong preference for high trans influence ligands to end up trans to tpy-N, whereas the lower trans influence ligands end up trans to tpy-C. Taking advantage of these preferences, tailor-made (N,C)Au(III) complexes could be prepared. For the functionalization of alkenes at (tpy)Au(OAcF)2, the higher trans effect of tpy-C would suggest that the coordination site trans to tpy-C would be kinetically more available than the one trans to tpy-N. However, due to the thermodynamic preference of having the σ-bonded ligand, resulting from the nucleophilic addition to alkenes, trans to tpy-N, functionalization of alkenes was only observed trans to tpy-N. However, for a catalytic process, the reaction should happen trans to tpy-C, as was observed for the trifluoroacetoxylation of acetylene. When functionalizing acetylene in the coordination site trans to tpy-N, protolytic cleavage of the Au-C(vinyl) bond to release the product did not occur at all, whereas trans to tpy-C protolytic cleavage of the Au-C(vinyl) bond occurred readily, in agreement with the higher trans influence of tpy-C over tpy-N. The large impact of the trans effects in Au(III) complexes is finally exemplified with the synthesis of [(tpy)Au(π-allyl)]+[NTf2]-, which resulted in a highly asymmetric π + σ bonding of the allyl moiety. Here, the bonding is such that the most thermodynamically favorable situation is achieved, with the carbon trans to tpy-N bonded in a σ-fashion and the π-allyl double bond being coordinated trans to tpy-C.


Patient satisfaction with video teleconsultation in a virtual diabetes outreach clinic.
This study assessed the level of patient satisfaction with diabetes remote consultations via videoconferencing in a virtual outreach clinic. A cross-sectional observational survey was conducted of people with diabetes who were living in regional cities of Queensland, Australia, and remotely consulted by endocrinologists at the Princess Alexandra Hospital tele-endocrinology clinic in Brisbane during autumn 2013. A questionnaire with 15 multiple-choice questions and one open-ended question was developed for assessing patient satisfaction with videoconferencing for specialty consultation. The questionnaire items showed strong internal consistency (Cronbach's α = 0.90). Patient satisfaction was assessed by this 16-item questionnaire exploring four dimensions: equipment/technical issues; communication and rapport; clinical assessment; and program evaluation. In total, 62 questionnaires were mailed to the patients, with 24 (39%) surveys completed and returned. The quality of video had the highest satisfaction rate (100%). The lowest satisfaction scores were reported in the "Clinical Assessment" dimension, in which 21% of respondents (five of 24) were concerned that the lack of physical contact could be a problem for managing their diabetes. The patients did not report any problem with building rapport with their consultant over the videoconference. The patients with diabetes who were seen remotely by endocrinologists via videoconferencing were generally satisfied with remote consultation. The questionnaire developed specifically for diabetes video teleconsultation in this study is useful for the measurement of patient satisfaction, and a modified version may be used in other clinical specialties.


The Transforming Growth Factor β1/Interleukin-31 Pathway Is Upregulated in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure and Is Associated with Disease Severity and Survival.
The transforming growth factor β1/interleukin-31 (TGF-β1/IL-31) pathway plays an important role in the process of cell injury and inflammation. The purpose of this work was to explore the role of the TGF-β1/IL-31 pathway in the cytopathic process of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). The quantitative serum levels of TGF-β1, IL-9, IL-10, IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were analyzed among chronic hepatitis B (CHB) patients (n = 17), ACLF patients (n = 18), and normal control (NC) subjects (n = 18). Disease severity in patients with ACLF was assessed using the model for end-stage liver disease (MELD) and Child-Pugh scores. Serum TGF-β1 levels were strongly positively correlated with IL-31 in all subjects, and both of them were positively correlated with IL-17, IL-22, and IL-33. In CHB and ACLF patients, serum levels of TGF-β1 and IL-31 were both increased significantly compared with those in NC subjects and positively correlated with total bilirubin (TBil) and alpha-fetoprotein (AFP) levels. ACLF patients showed the highest levels of TGF-β1 and IL-31, which were positively correlated with Child-Pugh scores. Furthermore, the recovery from the liver injury in CHB was accompanied by decreased TGF-β1 and IL-31 levels. More importantly, serum levels of TGF-β1 and IL-31 were markedly upregulated in ACLF nonsurvivors, and IL-31 displayed the highest sensitivity and specificity (85.7% and 100.0%, respectively) in predicting nonsurvival of ACLF patients. Increasing activity of the TGF-β1/IL-31 pathway is well correlated with the extent of liver injury, disease severity, and nonsurvival of ACLF patients, while reducing activity is detected along the recovery from liver injury in CHB, suggesting its potential role in the pathogenesis of liver injury during chronic HBV infection.


Reward processing in trichotillomania and skin picking disorder.
Trichotillomania (hair pulling disorder) and skin picking disorder are common and often debilitating mental health conditions, grouped under the umbrella term of body focused repetitive behaviors (BFRBs). Although the pathophysiology of BFRBs is incompletely understood, reward processing dysfunction has been implicated in the etiology and sustention of these disorders. The purpose of this study was to probe reward processing in BFRBs. 159 adults (125 with a BFRB [83.2% (n = 104) female] and 34 healthy controls [73.5% (n = 25) female]) were recruited from the community for a multi-center between-group comparison using a functional imaging (fMRI) monetary reward task. Differences in brain activation during reward anticipation and punishment anticipation were compared between BFRB patients and controls, with stringent correction for multiple comparisons. All group level analyses controlled for age, sex and scanning site. Compared to controls, BFRB participants showed marked hyperactivation of the bilateral inferior frontal gyrus (pars opercularis and pars triangularis) compared to controls. In addition, BFRB participants exhibited increased activation in multiple areas during the anticipation of loss (right fusiform gyrus, parahippocampal gyrus, cerebellum, right inferior parietal lobule; left inferior frontal gyrus). There were no significant differences in the win-lose contrast between the two groups. These data indicate the existence of dysregulated reward circuitry in BFRBs. The identified pathophysiology of reward dysfunction may be useful to tailor future treatments.


[Preparation of a standard diet for out-patients in the study of lithogenesis].
With the development of extracorporeal shock wave lithotripsy treatment, the duration of hospitalization for stone patients fortunately has become shorter. However, a detailed analysis of lithogenesis is not possible during such patients' short hospital stays. We prepared a standard diet to be eaten at home for investigation of lithogenesis at the out-patient clinic. This diet was nutritionally well-balanced and contained the following: energy: 2000 Kcal, total protein: 70-75 g, animal protein: 30-35 g, carbohydrate: 510 g, fat and oil: 50-60 g, calcium: 600-630 mg and magnesium: 320 mg. The urine of 24 male patients with stones on a free diet and the same patients after 3 days on the standard diet was analyzed for urea-nitrogen, uric acid, sodium, calcium, phosphorus, magnesium, citric acid and oxalic acid. The results were compared with those in 17 healthy male subjects who were eating the standard diet (controls). It was found that 66% of hypercalciuria (greater than = 300 mg/day) on a free diet became normocalciuria on the standard diet. The hypercalciuria was therefore thought to be of dietary origin. Moreover, urinary excretion of urea nitrogen, uric acid, sodium and phosphorus by patients remarkably decreased after 3 days on the standard diet, which was not different from that of controls. These results suggest that the standard diet at home is useful in the screening of hypercalciuria and also quite adequate for patients with stones.


Principles of rehabilitation and reactivation: interstitial lung disease, sarcoidosis and rheumatoid disease with respiratory involvement.
The interstitial lung diseases (ILDs) are characterised by dyspnoea on exertion, exercise-induced hypoxaemia, reduced skeletal muscle function and exercise intolerance. Evidence from nine randomised controlled trials shows that pulmonary rehabilitation improves exercise capacity, dyspnoea and quality of life in ILD, with moderately large effect sizes from 0.59 to 0.68. Participants with idiopathic pulmonary fibrosis, the most common and most progressive of the ILDs, achieve benefits in exercise capacity and quality of life that are of equal magnitude to those seen in other ILDs, with effect sizes from 0.59 to 0.75. Whole body exercise training is a core component of pulmonary rehabilitation for ILD. The standard exercise prescription used for other chronic lung diseases is effective in ILD, including 8 weeks of training with at least two supervised sessions per week and at least 30 min of aerobic training per session. However, the unique presentation and underlying pathophysiology of ILD may require modifications of the exercise prescription for individual patients. Those with connective tissue disease may present with joint pain and stiffness that require modification of the standard exercise prescription, including reduction in weight-bearing exercise. Some patients with severe disease may present with distressing dyspnoea that limits the intensity or progression of training. Because exercise-induced hypoxaemia is common in ILD and more severe than seen in other chronic lung diseases, pulmonary rehabilitation should be provided in a setting where supplemental oxygen therapy is available. Pulmonary rehabilitation programs offer the opportunity to address other critical aspects of ILD care, including management of comorbidities, symptoms and mood.


Facet joint changes after chemonucleolysis-induced disc space narrowing.
Changes on facet joint articular cartilage biology after chymopapain-induced disc height loss were determined in adult mongrel dogs. Disc height decreased to 50% at 2 weeks and returned to 80% at 6 months. The biochemistry and histology of the involved-level facet joints were followed at 2 weeks, 6 weeks, 3 months and 6 months after the injection. X-ray study showed a narrowing of the joint space and overlap of the facet joints at 6 weeks and at 3 months. Some return toward normal appearance was noted at 6 months. There was a loss of Safranin-O stain at 6 weeks, which persisted at 3 months, although some cells showed increased Safranin-O staining in the surrounding matrix. This was further improved at 6 months. The water content was unchanged early, but had decreased significantly at 6 weeks. The hexuronic acid content, already dropping at 2 weeks, was significantly lower at 6 weeks, at 3 months, and at 6 months. However, by 6 months, it had increased, compared with the 3-month value. Synthesis of proteoglycan was depressed only at 6 weeks. Similar changes were found in the facet cartilage in the joints above and below the last injected disc level. Results of this study would suggest that there is a cause-and-effect relationship between disc pathology and facet pathology and this can affect adjacent disc facet-joint biology. The initial facet lesion described appears to be potentially reversible, but a long-term disc height decrease might be expected to cause irreversible osteoarthritic-like changes in the adjacent facet joint.


A duplex probe-directed recombinase amplification assay for detection of single nucleotide polymorphisms on 8q24 associated with prostate cancer.
Single nucleotide polymorphisms (SNPs) have important application value in the research of population genetics, hereditary diseases, tumors, and drug development. Conventional methods for detecting SNPs are typically based on PCR or DNA sequencing, which is time-consuming, costly, and requires complex instrumentation. In this study, we present a duplex probe-directed recombinase amplification (duplex-PDRA) assay that can perform real-time detection of two SNPs (rs6983267 and rs1447295) in four reactions in two tubes at 39°C within 30 min. The sensitivity of duplex-PDRA was 2×103-104 copies per reaction and no cross-reactivity was observed. A total of 382 clinical samples (179 prostate cancer patients and 203 controls) from northern China were collected and tested by duplex-PDRA assay and direct sequencing. The genotyping results were completely identical. In addition, the association analysis of two SNPs with prostate cancer risk and bone metastasis was conducted. We found that the TT genotype of rs6983267 (OR: 0.42; 95%CI: 0.23-0.78; P=0.005) decreased the risk of prostate cancer, while the CA genotype of rs1447295 (OR: 1.89; 95%CI: 1.20-2.96; P=0.005) increased the risk of prostate cancer. However, no association between the two SNPs (rs6983267 and rs1447295) and bone metastasis in prostate cancer was found in this study (P>0.05). In conclusion, the duplex-PDRA assay is an effective method for the simultaneous detection of two SNPs and shows great potential for widespread use in research and clinical settings.


Plasma membrane microparticles in angiogenesis: role in ischemic diseases and in cancer.
Microparticles are small fragments of the plasma membrane released by activated and/or apoptotic cells. In theory, all type of cells can shed microparticles representing a physiological process in the cell life. Mainly, microparticles generation has been studied in different cardiovascular pathologies due to the facility to obtain blood samples from individuals. Although microparticles have been considered as simply markers of several diseases, in the last decade, several studies support the hypothesis that they participate in the regulation of the cardiovascular system function by carrying biological messages between cells. Among the effects of microparticles, recent data show that they can be implicated in the modulation of neovascularization, an essential function of cells from cardiovascular system during either ischemic diseases or cancer development. Whereas during pathologies associated with ischemia an increase of neovascularization may have beneficial effects, anti-angiogenic strategies represent new approaches for manipulation of tumor development. Here, we give an overview of the mechanisms and factors involved in neovascularization, and finally, we look at the role and the consequences of the modulation of this process by microparticles in pathological situations.


Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: role of vinegar in Irukandji syndrome.
A shortcut review was carried out to establish whether dousing areas of contact with vinegar could relieve the symptoms of Irukandji syndrome. Four studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is there is a lack of evidence for effectiveness and the latest local guidelines should be followed.


Brain volumes in relatives of patients with schizophrenia: a meta-analysis.
Smaller brain volumes have consistently been found in patients with schizophrenia, particularly in gray matter and medial temporal lobe structures. Although several studies have investigated brain volumes in nonpsychotic relatives of patients with schizophrenia, results have been inconsistent. To determine the magnitude and extent of brain volume differences in first-degree relatives of schizophrenic patients. A systematic search was conducted to identify relevant studies. Computer searches of the MEDLINE database were performed for English-language articles published before July 2005. Relevant abstracts published in 2005 were also selected. Magnetic resonance imaging studies that examined differences in brain volumes between first-degree relatives of patients with schizophrenia and healthy control subjects were obtained through computerized databases, including MEDLINE. Studies had to report sufficient data for computation of effect sizes. For each study, the Cohen d was calculated. Data extraction and calculation of the effect size were performed by 2 authors (H.B.M.B. and A.A.) who reached a consensus in cases of uncertainty and discrepancies. All analyses were performed using the random-effects model. Twenty-five studies were identified as suitable for analysis and included 1065 independent first-degree relatives of patients, 679 patients with schizophrenia, and 1100 healthy control subjects. The largest difference between relatives and healthy control subjects was found in hippocampal volume, with relatives having smaller volumes than controls (d = 0.31; 95% confidence interval [CI], 0.13-0.49; 9 effect sizes). Gray matter was smaller (d = 0.18; 95% CI, 0.02-0.33; 7 effect sizes) and third-ventricle volume was larger (d = 0.21; 95% CI, 0.03-0.40; 7 effect sizes) in relatives compared with healthy control subjects. Brain abnormalities are present in nonpsychotic first-degree relatives of patients with schizophrenia and are most pronounced in the hippocampus.


Bibliometric study of the systematic reviews and meta-analyses in dentistry.
Scientific production has increased in the last decades, consequently the number of systematic reviews, reviews and meta-analyses, the objective is to carry out a bibliometric analysis study of systematic reviews and meta-analyses in dentistry, divided into different thematic areas. A search was conducted in the Science Citation Index-Expanded on the core collection of Web of Science, they were selected from the area of Dentistry and Oral Surgery and Medicine categories, the data was downloaded on April 20, 2022 and The 100 most cited articles from each of the thematic areas were selected. An increase in this type of articles was observed in the last decade in the areas of pediatric and medical dentistry and oral pathology. The thematic area that received the most citations was periodontics. The two authors with the most citations are Zwahlen, Marcel and Pjetursson, Bjarni Eluar. The countries that receive the most citations are European, along with the USA and China. The topics that are most published in this type of article deal with Cancer with 50 publications, caries treatment with 25 and fluoridation with 1. The entities that finance this type of articles the most are private companies (26.76%). Together with an exponential increase in the number of publications in dentistry, there has been an increase in the number of publications in systematic reviews. The areas publishing the most articles and having the most citations are Periodontics and Implantology, despite the fact that the most studied topic is cancer. Key words:Bibliometrics, methodological study, systematics reviews, metanalys.


Anatomo-Physiologic Basis for Auricular Stimulation.
Introduction: Stimulation of cranial nerves modulates central nervous system (CNS) activity via the extensive connections of their brainstem nuclei to higher-order structures. Clinical experience with vagus-nerve stimulation (VNS) demonstrates that it produces robust therapeutic effects, however, posing concerns related to its invasiveness and side-effects. Discussion: Trigeminal nerve stimulation (TNS) has been recently proposed as a valid alternative to VNS. The ear presents afferent vagus and trigeminal-nerve distribution; its innervation is the theoretical basis of different reflex therapies, including auriculotherapy. An increasing number of studies have shown that several therapeutic effects induced by invasive VNS and TNS, can be reproduced by noninvasive auricular-nerve stimulation. However, the sites and neurobiologic mechanisms by which VNS and TNS produce their therapeutic effects are not clear yet. Conclusions: Accumulating evidence suggests that VNS and TNS share multiple levels and mechanisms of action in the CNS.


Gintonin Alleviates HCl/Ethanol- and Indomethacin-Induced Gastric Ulcers in Mice.
Gintonin, newly extracted from ginseng, is a glycoprotein that acts as an exogenous lysophosphatidic acid (LPA) receptor ligand. This study aimed to demonstrate the in vivo preventive effects of gintonin on gastric damage. ICR mice were randomly assigned to five groups: a normal group (received saline, 0.1 mL/10 g, p.o.); a control group (administered 0.3 M HCl/ethanol, 0.1 mL/10 g, p.o.) or indomethacin (30 mg/kg, p.o.); gintonin at two different doses (50 mg/kg or 100 mg/kg, p.o.) with either 0.3 M HCl/ethanol or indomethacin; and a positive control (Ranitidine, 40 mg/kg, p.o.). After gastric ulcer induction, the gastric tissue was examined to calculate the ulcer index. The expression of gastric damage markers, such as tumor necrosis factor (TNF)-α, cyclooxygenase 2 (COX-2), and LPA2 and LPA5 receptors, were measured by Western blotting. Interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were measured by enzyme-linked immunosorbent assay. The platelet endothelial cell adhesion molecule (PECAM-1), Evans blue, and occludin levels in gastric tissues were measured using immunofluorescence analysis. Both HCl/ethanol- and indomethacin-induced gastric ulcers showed increased TNF-α, IL-6, Evans blue permeation, and PECAM-1, and decreased COX-2, PGE2, occludin, and LPA5 receptor expression levels. However, oral administration of gintonin alleviated the gastric ulcer index induced by HCl/ethanol and indomethacin in a dose-dependent manner. Gintonin suppressed TNF-α and IL-6 expression, but increased COX-2 expression and PGE2 levels in mouse gastric tissues. Gintonin intake also increased LPA5 receptor expression in mouse gastric tissues. These results indicate that gintonin can play a role in gastric protection against gastric damage induced by HCl/ethanol or indomethacin.


Seed storage proteins as a system for teaching protein identification by mass spectrometry in biochemistry laboratory.
Mass spectrometry (MS) has become an important tool in studying biological systems. One application is the identification of proteins and peptides by the matching of peptide and peptide fragment masses to the sequences of proteins in protein sequence databases. Often prior protein separation of complex protein mixtures by 2D-PAGE is needed, requiring more time and expertise than instructors of large laboratory classes can devote. We have developed an experimental module for our Biochemistry Laboratory course that engages students in MS-based protein identification following protein separation by one-dimensional SDS-PAGE, a technique that is usually taught in this type of course. The module is based on soybean seed storage proteins, a relatively simple mixture of proteins present in high levels in the seed, allowing the identification of the main protein bands by MS/MS and in some cases, even by peptide mass fingerprinting. Students can identify their protein bands using software available on the Internet, and are challenged to deduce post-translational modifications that have occurred upon germination. A collection of mass spectral data and tutorials that can be used as a stand-alone computer-based laboratory module were also assembled.


Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease.
This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI). Baseline demographics were similar between the treatment groups. Least squares mean (+/- SE) baseline NPI 12-item total scores were 19.55 +/- 1.48 and 19.30 +/- 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI (continued) 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.


Survival models with preclustered gene groups as covariates.
An important application of high dimensional gene expression measurements is the risk prediction and the interpretation of the variables in the resulting survival models. A major problem in this context is the typically large number of genes compared to the number of observations (individuals). Feature selection procedures can generate predictive models with high prediction accuracy and at the same time low model complexity. However, interpretability of the resulting models is still limited due to little knowledge on many of the remaining selected genes. Thus, we summarize genes as gene groups defined by the hierarchically structured Gene Ontology (GO) and include these gene groups as covariates in the hazard regression models. Since expression profiles within GO groups are often heterogeneous, we present a new method to obtain subgroups with coherent patterns. We apply preclustering to genes within GO groups according to the correlation of their gene expression measurements. We compare Cox models for modeling disease free survival times of breast cancer patients. Besides classical clinical covariates we consider genes, GO groups and preclustered GO groups as additional genomic covariates. Survival models with preclustered gene groups as covariates have similar prediction accuracy as models built only with single genes or GO groups. The preclustering information enables a more detailed analysis of the biological meaning of covariates selected in the final models. Compared to models built only with single genes there is additional functional information contained in the GO annotation, and compared to models using GO groups as covariates the preclustering yields coherent representative gene expression profiles.


Novel, complex interruptions of the GAA repeat in small, expanded alleles of two affected siblings with late-onset Friedreich ataxia.
Friedreich ataxia (FA) is an autosomal recessive disorder associated with expanded GAA repeats in intron 1 of the FRDA gene. Two siblings presented with a mild form of FA at >60 years of age. Both had a large expansion (>600 repeats) and a small expansion (120 repeats) by long-range PCR. Sequence analysis of the small allele revealed multiple, complex interruptions in the GAA repeat. These 2 patients presented later than predicted from their allele size alone, when compared with a large cohort of FA patients. Accounting for the interruptions in the GAA repeat, though, did not make the age of onset consistent with that noted in other patients. Three additional patients with late onset FA and small expanded alleles also exhibited interrupted GAA repeats that were not associated with inappropriately late onset. Our observations suggest that interrupted GAA repeats do not clearly impact the age of onset in FA.


Carotid stenting done exclusively by vascular surgeons: first 175 cases.
Percutaneous CAS may well replace CEA as standard of care. CAS has been performed largely by interventional cardiologists; however, with recent Food and Drug Administration approval, vascular surgeons are now hurriedly attempting to obtain the requisite endovascular skills. Reported are our 30-day and midterm outcomes of CAS. Retrospective review of 175 cervical carotid stenoses treated with elective CAS from April 2001 to February 2005. All procedures were performed under local anesthesia via percutaneous femoral access in an operating room angiosuite. Mechanical cerebral protection was used in 90% of cases. Data analysis includes demographics, procedural records, and duplex exams over a mean follow-up of 21 months. Mean age is 70 years (74% men and 26% women). Preprocedural neurologic symptoms were present in 32%. Intraoperative complications included 2 seizures (1.1%) and 4 asystolic arrests (2.3%), all managed medically without sequelae. Over the 30-day follow-up there were no deaths, no myocardial infarctions (MIs), 2 major strokes (1.1%), 2 minor strokes (1.1%), 3 transient ischemic attacks (TIAs) (1.7%), and 1 major access-site complication (0.6%). At late follow-up, 3 cases (1.7%) of restenosis occurred; all were treated with repeat angioplasty and remain patent. One (0.6%) asymptomatic occlusion was detected at 6-month follow-up. There have been no late carotid-related complications or deaths. Vascular surgeons possessing advanced catheter-based skills can safely perform CAS and achieve perioperative results comparable to CEA. Such skills are crucial to those surgeons intent on the future management of carotid occlusive disease.


Genistein-Opportunities Related to an Interesting Molecule of Natural Origin.
Nowadays, increasingly more attention is being paid to a holistic approach to health, in which diet contributes to disease prevention. There is growing interest in functional food that not only provides basic nutrition but has also been demonstrated to be an opportunity for the prevention of disorders. A promising functional food is soybean, which is the richest source of the isoflavone, genistein. Genistein may be useful in the prevention and treatment of such disorders as psoriasis, cataracts, cystic fibrosis, non-alcoholic fatty liver disease and type 2 diabetes. However, achievable concentrations of genistein in humans are low, and the use of soybean as a functional food is not devoid of concerns, which are related to genistein's potential side effects resulting from its estrogenic and goitrogenic effects.


Evidence of duration and type of illness in children found unexpectedly dead.
The thymus, rib, and liver from a series of 200 children found unexpectedly dead showed that in over 90% of these children the costochondral junction indicated that a retardation in growth velocity had preceded death. In a similar proportion of children the liver showed fatty change indicating a metabolic upset, which in 5% was of severe degree. Changes in the thymus compatible with a normal reaction to infection were observed in only a little over half of the child deaths. An absence of gross thymic reaction in some children in whom there was other evidence of infection suggests that in some an abnormal immunological reaction was taking place. It is concluded that careful systematic clinical monitoring of growth in these children would have shown abnormality in nearly all.


Devices for low flow O2 administration.
Long-term oxygen therapy requires a practical regulated oxygen delivery system which works in the home. Although face-masks are cheap and efficient, they are awkward and need removal for talking and eating. Few patients would comply with this for 15 h her day. Nasal prongs are reliable, cheap, safe and well tolerated but are wasteful of oxygen. This waste is important both practically and financially when oxygen is supplied from portable or large cylinders or from a liquid source. The Oxymizer pendants and moustache or inspiration phased delivery devices improve nasal prong efficiency. Nasopharyngeal catheters are an alternative but more invasive means of oxygen conservation. Percutaneous transtracheal catheterization is both oxygen efficient and cosmetically acceptable. As it requires an invasive surgical procedure with some serious potential complications its use should probably be reserved for those patients in whom adequate oxygenation is not achieved by standard nasal prongs. Its use is rarely justified on merely cosmetic grounds. Permanent tracheostomy is not indicated in most cases of hypoxic chronic obstructive airways disease (COAD). Nasal prongs would seem the most reasonable method of oxygen delivery. Their use with oxygen concentrators lessens the need for oxygen conservation.


DERnet: a deep neural network for end-to-end reconstruction in magnetic particle imaging.
Magnetic particle imaging (MPI) shows potential for contributing to biomedical research and clinical practice. However, MPI images are effectively affected by noise in the signal as its reconstruction is an ill-posed inverse problem. Thus, effective reconstruction method is required to reduce the impact of the noise while mapping signals to MPI images. Traditional methods rely on the hand-crafted data-consistency (DC) term and regularization term based on spatial priors to achieve noise-reducing and reconstruction. While these methods alleviate the ill-posedness and reduce noise effects, they may be difficult to fully capture spatial features. In this study, we propose a deep neural network for end-to-end reconstruction (DERnet) in MPI that emulates the DC term and regularization term using the feature mapping subnetwork and post-processing subnetwork, respectively, but in a data-driven manner. By doing so, DERnet can better capture signal and spatial features without relying on hand-crafted priors and strategies, thereby effectively reducing noise interference and achieving superior reconstruction quality. Our data-driven method outperforms the state-of-the-art algorithms with an improvement of 0.9-8.8dB in terms of peak signal-to-noise ratio under various noise levels. The result demonstrates the advantages of our approach in suppressing noise interference. Furthermore, DERnet can be employed for measured data reconstruction with improved fidelity and reduced noise. In conclusion, our proposed method offers performance benefits in reducing noise interference and enhancing reconstruction quality by effectively capturing signal and spatial features. DERnet is a promising candidate method to improve MPI reconstruction performance and facilitate its more in-depth biomedical application.


Through education we can grow.
A Registry Examination for optometric technicians was administered to 189 students and graduate optometric technicians on April 19, 1980. Those who passed this examination will be designated as members of the National paraoptometric Registry. A Registry Examination for optometric assistants is being developed for administration in April 1981. This article will outline how these Registry Examination were developed and what implications they have for the profession. A paraoptometric career ladder will also be presented.


Polymeric IgA-secreting and mucosal homing pre-plasma cells in normal human peripheral blood.
Clear identification of recently activated mucosal B cells in human blood would greatly facilitate study of mucosal vaccines, immune response to infection and the ongoing mucosal IgA response. We examined blood lymphocytes from normal, healthy individuals to identify IgA-secreting pre-plasma cells' (PPC) functional and phenotypic relevance to mucosal antibody production, in the absence of infection, disease or recent vaccination. PPC are the most recently activated B lymphocytes in blood and are considered in transit between lymphoid tissue and effector tissues, where they terminally differentiate into plasma cells. We observed that all IgA-secreting PPC expressed surface IgA (sIgA) and intracellular IgA (icIgA) and secreted primarily polymeric IgA (pIgA), as determined by flow cytometry, ELISPOT and size exclusion chromatography. A large sub-population of PPC in blood expresses the mucosal chemokine receptor CCR10 and contains the largest fraction of sIgA and icIgA PPC that secrete pIgA. The majority of CCR10(+) PPC expresses high levels of Ki67, indicative of recently activated blasts. In contrast, most CCR10(-) PPC secrete IgG, but a small population secretes pIgA and stains for icIgA. The mucosal integrin alpha(4)beta(7) was detected on a subset of PPC, but this subset did not account for all CCR10(+) PPC or all PPC with sIgA expression. Our data clearly demonstrate that PPC defined by surface expression of CD19, CD27(hi), IgA and CCR10 secrete only pIgA and are the dominant mucosal PPC subset in human blood. These mucosal PPC can now be investigated routinely as indicators of recent human mucosal IgA responses.


The relationship between terminal functionalization and molecular weight of a gene delivery polymer and transfection efficacy in mammary epithelial 2-D cultures and 3-D organotypic cultures.
Non-viral gene delivery vectors were developed for efficient gene transfer to hard-to-transfect mouse mammary epithelial cells. Ten modified versions of the same base poly(beta-amino ester), poly(1,4-butanediol diacrylate-co-5-amino-1-pentanol), were tested in both traditional 2-D monolayer and in 3-D organotypic cultures. The polymers self-assembled with plasmid DNA encoding enhanced green fluorescent protein to form nanoparticles (approximately 100 nm) used to transfect the cells. Nanoparticle transfection efficacy was tuned by changes in synthesis and fabrication conditions and the transfection efficacy was analyzed using confocal microscopy and flow cytometry. The best performing polymeric nanoparticles transfected 57 +/- 6% of the cells in 2-D culture and 6 +/- 1% of the cells in 3-D culture. Small modifications to the polymer end-capping molecules and tuning of polymer molecular weight could either significantly enhance the transfection efficacy up to 6-fold or instead abolish efficacy completely. The efficacy of leading polymers was higher than that of the commercial transfection agent FuGENE HD by a factor of 13 in 2-D and 2 in 3-D. These non-viral nanoparticles may be useful as delivery reagents or targeted therapeutics for breast cancer. This gene delivery strategy is also a promising approach for studying the normal development of the mammary gland.


Use of inhaled devices during a hospital exacerbation of COPD: a summary of an interdisciplinary audit held at ICS Maugeri Pavia, Italy (March-June 2019).
To date treatment protocols in Respiratory and or Internal departments across Italy for treatment of chronic obstructive pulmonary disease (COPD) patients at hospital admission with relapse due to exacerbation do not find adequate support in current guidelines. Here we describe the results of a recent clinical audit, including a systematic review of practices reported in literature and an open discussion comparing these to current real-life procedures. The process was dived into two 8-hour-audits 3 months apart in order to allow work on the field in between meeting and involved 13 participants (3 nurses, 1 physiotherapist, 2 internists and 7 pulmonologists). This document reports the opinions of the experts and their consensus, leading to a bundle of multidisciplinary statements on the use of inhaled drugs for hospitalized COPD patients. Recommendations and topics addressed include: i) monitoring and diagnosis during the first 24 h after admission; ii) treatment algorithm and options (i.e., short and long acting bronchodilators); iii) bronchodilator dosages when switching device or using spacer; iv) flow measurement systems for shifting to LABA+LAMA within 48 h; v) when nebulizers are recommended; vi) use of SMI to deliver LABA+LAMA when patient needs SABA <3 times/day independently from flow limitation; vii) use of DPI and pre-dosed MDI to deliver LABA+LAMA or TRIPLE when patient needs SABA <3 times/day, with inspiratory flow > 30 litres/min; viii) contraindication to use DPI; ix) continuation of LABA-LAMA when patient is already on therapy; x) possible LABA-LAMA dosage increase; xi) use of SABA and/or SAMA in addition to LABA+LABA; xii) use of SABA+SAMA restricted to real need; xiii) reconciliation of drugs in presence of comorbidities; xiv) check of knowledge and skills on inhalation therapy; xv) discharge bundle; xvi) use of MDI and SMI in tracheostomized patients in spontaneous and ventilated breathing.


Establishment of an in vitro cell model system to study human prostate carcinogenesis.
A positive family history of prostate cancer is a risk factor for this disease, suggesting that alterations of certain genes may play an important role in the development and progression of prostate cancer. However, genetic alterations responsible for initiation and acquisition of metastatic phenotypes by prostate cancer are not well defined. We have observed a consistent change in chromosome 5 in an in vitro cell model of human prostate carcinogenesis in which the near-diploid cells from the surrounding tissue of an adenocarcinoma of the prostate obtained from a 42-year-old patient were subjected to in vitro cell culture and passages. We have examined three different passages of this cell strain by conventional and molecular cytogenetic methods and have seen an increased number of alterations in chromosome 5 in higher passage cells, with accompanying changes in cell morphology. In late passages of this cell line, no cell showed two normal copies of chromosome 5 as analyzed by G-banding and fluorecent in situ hybridization (FISH). The long arm (q) of chromosome 5 was either missing or involved in structural rearrangements. This observation suggests that the q arm of chromosome 5 may carry a tumor suppressor gene(s) that is well-expressed in normal prostate tissue, but when one of these tumor suppressor gene(s) is mutated or deleted and its encoded mRNA and protein are differentially expressed or not expressed at all in the prostate cells, then it may lead to initiation of tumor growth and development. Cytogenetic analyses of early passage cells in this cell strain revealed that approximately 78.8% of metaphases were normal, with a 46,XY chromosome constitution, and 21.2% of cells had clonal alterations mostly of chromosomes 5, 7, 8, 15, 16 and Y. In the middle passages, abnormal cells increased in number (78.26%) and also showed a large number of chromosomal changes. In the late passages, all cells showed structural and numerical abnormalities of the same chromosomes, in addition to some new markers; no cells were found to have a normal karyotype. These chromosomal aberrations could be considered early markers of prostate carcinogenesis. Some of the markers present in late passage cells were similar to those reported in a well-characterized prostate cancer cell line, LNCaP.


High-power supercontinuum generation by noise-like pulse amplification in Yb-doped fiber amplifier operating in a nonlinear regime.
In this paper, we report on a supercontinuum generation by amplifying noise-like pulses (NLPs) in a nonlinear Yb-doped fiber amplifier. The NLP source is a homemade Yb-doped all-fiber ring oscillator based on nonlinear polarization rotation mode-locking method. NLPs possess a repetition rate of 11.57 MHz, energy of 16.5 nJ, and 3 dB spectral bandwidth of 42 nm. The intensity autocorrelation function of NLPs has a broad pedestal and a narrow central spike. The pedestal and the spike have temporal widths of 63 ps and 92 fs, respectively. The NLPs are amplified by a Yb-doped fiber nonlinear power amplifier to achieve output power of 7.5 W. Nonlinear effects in the amplifier drastically broaden the spectrum of NLPs and generate high-power supercontinuum light with 10 dB spectral bandwidth of 1130 nm (from 1037 to 2167 nm). The presented supercontinuum generation system is an all-fiber compact structure and has the advantage of not requiring long single-mode, nonlinear, or photonic crystal fibers.


Interrogation of global active site occupancy of a fungal iterative polyketide synthase reveals strategies for maintaining biosynthetic fidelity.
Nonreducing iterative polyketide synthases (NR-PKSs) are responsible for assembling the core of fungal aromatic natural products with diverse biological properties. Despite recent advances in the field, many mechanistic details of polyketide assembly by these megasynthases remain unknown. To expand our understanding of substrate loading, polyketide elongation, cyclization, and product release, active site occupancy and product output were explored by Fourier transform mass spectrometry using the norsolorinic acid anthrone-producing polyketide synthase, PksA, from the aflatoxin biosynthetic pathway in Aspergillus parasiticus. Here we report the simultaneous observation of covalent intermediates from all catalytic domains of PksA from in vitro reconstitution reactions. The data provide snapshots of iterative catalysis and reveal an underappreciated editing function for the C-terminal thioesterase domain beyond its recently established synthetic role in Claisen/Dieckmann cyclization and product release. The specificity of thioesterase catalyzed hydrolysis was explored using biosynthetically relevant protein-bound and small molecule acyl substrates and demonstrated activity against hexanoyl and acetyl, but not malonyl. Processivity of polyketide extension was supported by the inability of a nonhydrolyzable malonyl analog to trap products of intermediate chain lengths and by the detection of only fully extended species observed covalently bound to, and as the predominant products released by, PksA. High occupancy of the malonyl transacylase domain and fast relative rate of malonyl transfer compared to starter unit transfer indicate that rapid loading of extension units onto the carrier domain facilitates efficient chain extension in a manner kinetically favorable to ultimate product formation.


[The use of fenazid in patients with pulmonary tuberculosis with poor isoniazid tolerance].
The paper shows the experience gained in the use of the new Russian antituberculous drug fenazid in patients with different forms of active pulmonary tuberculosis and with neuro- and angiotoxic reactions to isoniazid. The study group comprised 25 patients aged 23 to 70 years who received fenazid as tablets in a daily dose of 0.5 g for 2 months at the first stage of the basic course of chemotherapy. The control group including 24 patients of the same age was given the routine antituberculous chemotherapy regimen, including isoniazid. The use of fenazid permits adequate therapy in patients with poor isoniazid tolerance, which may recommend fenazid to individuals at high risk for adverse reactions as their prevention.


Atopobacter phocae gen. nov., sp. nov., a novel bacterium isolated from common seals.
Two strains of a Gram-positive, catalase-negative, facultatively anaerobic, rod-shaped bacterium isolated from common seals were characterized using phenotypic and molecular taxonomic methods. The two strains closely resembled each other based on their biochemical characteristics, and PAGE analysis of whole-cell protein patterns confirmed their close phenotypic affinity. 16S rRNA gene sequencing showed that the two strains were genetically highly related (99.8% sequence similarity) and that they constitute a new line of descent within the lactic acid group of bacteria. The nearest phylogenetic neighbours of the unknown bacterium were Granulicatella spp., with related taxa such as enterococci, carnobacteria, Desemzia incerta, Lactosphaera pasteurii, Melissococcus plutonius, tetragenococci and vagococci more distantly related. Based on phylogenetic and phenotypic evidence it is proposed that the unknown bacterium from seals be classified in a new genus as Atopobacter phocae gen. nov., sp. nov. The type strain of Atopobacter phocae is CCUG 42358T (= CIP 106392T).


Cryptorchidism in Children with Zika-Related Microcephaly.
The genitourinary tract was recently identified as a potential site of complications related to the congenital Zika syndrome (CZS). We provide the first report of a series of cryptorchidism cases in 3-year-old children with Zika-related microcephaly who underwent consultations between October 2018 and April 2019 as part of the follow-up of the children cohort of the Microcephaly Epidemic Research Group, Pernambuco, Brazil. Of the 22 males examined, eight (36.4%) presented with cryptorchidism. Among 14 undescended testis cases, 11 (78.6%) could be palpated in the inguinal region. Seven of the eight children had severe microcephaly. Conventional risk factors for cryptorchidism were relatively infrequent in these children. We hypothesize that cryptorchidism is an additional manifestation of CZS present in children with severe microcephaly. As in our cases, for most of the children, the testes were located in the inguinal region, and the possible mechanisms for cryptorchidism were gubernaculum disturbance or cremasteric abnormality.


Career choice of tourism students in a triple-whammy crisis.
Hong Kong hospitality and tourism industry has been battered by the triple whammy of social unrest, Sino-US trade war and COVID-19 pandemic in recent years. To understand how vulnerable tourism students may be in terms of career shock when facing the three major challenges, 407 tourism students in Hong Kong were surveyed. Structural equation modelling found a positive correlation between affect (an intrinsic, motivating factor) and extraneous events (an extrinsic, demotivating factor), indicating that motivation and demotivating factors may co-exist. Affect was more positively correlated with three career choice outcomes (intent to join the industry, desire for a lifelong career, and resilience in face of unfavourable circumstances) than was Extraneous. In face of career shock arising from extraneous events, tourism students still tend to have a strong intent to join the workforce, take it as a lifelong career, and remain resilient despite the hardship. However, the career shock was a greater concern for those in hotel-related disciplines and for students aged over 20 than younger ones. The findings offer an empirical basis to guide policy makers, academia and the industry in strategy formulation to ensure sustainable quality and manpower supply in the post-crisis future.


Cervical kyphosis in patients who have Larsen syndrome.
Four patients who had Larsen syndrome and cervical kyphosis were managed operatively and followed for an average of seventy months (range, forty to ninety-two months). The preoperative cervical kyphosis ranged from 35 to 65 degrees. The patients had had a posterior cervical arthrodesis alone when they were infants, at an average age fo fourteen months (range, ten to sixteen months). In three infants, the kyphosis either stabilized (one patient) or reversed into lordosis (two patients). Thus, the kyphosis corrected gradually by continued anterior growth in the presence of a solid posterior fusion. In the fourth infant, the kyphosis progressed to 110 degrees because of pseudarthrosis. This child had anterior decompression and arthrodesis for an acute neurological deficit. We believe that cervical kyphosis is sometimes present but not diagnosed in patients who have Larsen syndrome. Early diagnosis followed by operative stabilization should help such patients avoid neurological deficits. Posterior cervical arthrodesis alone, performed in infancy, provided stability and the opportunity for the gradual correction of the deformity by continued anterior growth in three of our four patients.


Recurrent dislocation of the proximal tibiofibular joint.
Recurrent dislocation of the proximal tibiofibular joint is a rare injury. This report presents a case of bilateral recurrent dislocations of the proximal tibiofibular joint in a jet skier that responded to physical therapy and activity modification. A review of the literature is provided, with attention to the mechanism of injury and other treatment options--including arthrodesis and resection of the proximal fibula. This diagnosis should be considered in jet skiers with lateral-sided knee pain.


Climate change influences on marine infectious diseases: implications for management and society.
Infectious diseases are common in marine environments, but the effects of a changing climate on marine pathogens are not well understood. Here we review current knowledge about how the climate drives host-pathogen interactions and infectious disease outbreaks. Climate-related impacts on marine diseases are being documented in corals, shellfish, finfish, and humans; these impacts are less clearly linked for other organisms. Oceans and people are inextricably linked, and marine diseases can both directly and indirectly affect human health, livelihoods, and well-being. We recommend an adaptive management approach to better increase the resilience of ocean systems vulnerable to marine diseases in a changing climate. Land-based management methods of quarantining, culling, and vaccinating are not successful in the ocean; therefore, forecasting conditions that lead to outbreaks and designing tools/approaches to influence these conditions may be the best way to manage marine disease.


In search of the RNA world on Mars.
Advances in origins of life research and prebiotic chemistry suggest that life as we know it may have emerged from an earlier RNA World. However, it has been difficult to reconcile the conditions used in laboratory experiments with real-world geochemical environments that may have existed on the early Earth and hosted the origin(s) of life. This challenge is due to geologic resurfacing and recycling that have erased the overwhelming majority of the Earth's prebiotic history. We therefore propose that Mars, a planet frozen in time, comprised of many surfaces that have remained relatively unchanged since their formation > 4 Gya, is the best alternative to search for environments consistent with geochemical requirements imposed by the RNA world. In this study, we synthesize in situ and orbital observations of Mars and modeling of its early atmosphere into solutions containing a range of pHs and concentrations of prebiotically relevant metals (Fe2+ , Mg2+ , and Mn2+ ) spanning various candidate aqueous environments. We then experimentally determine RNA degradation kinetics due to metal-catalyzed hydrolysis (cleavage) and evaluate whether early Mars could have been permissive toward the accumulation of long-lived RNA polymers. Our results indicate that a Mg2+ -rich basalt sourcing metals to a slightly acidic (pH 5.4) environment mediates the slowest rates of RNA cleavage, though geologic evidence and basalt weathering models suggest aquifers on Mars would be near neutral (pH ~ 7). Moreover, the early onset of oxidizing conditions on Mars has major consequences regarding the availability of oxygen-sensitive metals (i.e., Fe2+ and Mn2+ ) due to increased RNA degradation rates and precipitation. Overall, (a) low pH decreases RNA cleavage at high metal concentrations; (b) acidic to neutral pH environments with Fe2+ or Mn2+ cleave more RNA than Mg2+ ; and (c) alkaline environments with Mg2+ dramatically cleaves more RNA while precipitates were observed for Fe2+ and Mn2+ .