Decreased cerebellar posterior vermis size in fragile X syndrome: correlation with neurocognitive performance.
We examined whether posterior vermis size is smaller in individuals with fragile X syndrome (fra X) than in control subjects and whether this decreased size is associated with cognitive performance. Cognitive and behavioral dysfunctions have been identified in fra X; however, underlying neuropathogenic mechanisms remain unclear. MRI was used to investigate the posterior fossa in 32 males with fra X, 28 males with other causes of cognitive disability (CD), and 38 males with normal development (ND) as well as and in 37 females with fra X and 53 female control subjects. Among females with fra X, neurocognitive correlates of posterior vermis size were examined. Posterior vermis size (cross-sectional area) in males with fra X was significantly smaller compared with CD and ND groups, particularly when corrected for intracranial area. Posterior vermis size corrected for intracranial area was significantly smaller in females with fra X compared with control subjects. Compared with males with fra X and non-fra X control subjects, posterior vermis size in females with fra X was intermediate. After statistically removing the effect of mean parental IQ, posterior vermis size predicted a significant proportion of the variance (10 to 23%) of performance on full-scale, verbal, and performance IQ; block design; categories achieved on the Wisconsin Card Sorting Test; and the Rey inventory score. The size of the posterior vermis is significantly decreased in fra X, more so in males than in females. In females with fra X, posterior vermis size predicts performance on selected cognitive measures.


[Does sea-grass biomass control the density of peracarids (Crustacea: Peracarida) in tropical lagoons?].
We analyzed the time-space variation of the peracarid crustaceans that inhabit seagrasses of the Alvarado Lagoon System, Veracruz, Gulf of Mexico. The organisms were collected from 108 samples in six sites with Ruppia maritima beds (December 1992 to November 1994). The assemblage was composed of 11 species. Eight species of Amphipoda (Hourstonius laguna, Cerapus benthophilus, Apocorophium louisianum, Grandidierella bonnieroides, Leptocheirus rhizophorae, Gammarus mucronatus, Melita longisetosa and Haustorius sp.), one of Isopoda (Cassidinidea ovalis) and two of Tanaidacea (Discapseudes holthuisi and Leptochelia savignyi) were identified. Taxocoenosis, density and biomass of peracarids showed seasonal pulses related to R. maritima biomass, salinity variation, epicontinental affluent and inlets. The species C. ovalis, G. mucronatus, A. louisianum and D. holthuisi were dominant.


Absence of interaction between atorvastatin or other statins and clopidogrel: results from the interaction study.
Some, but not all, post hoc analyses have suggested that the antiplatelet effects of clopidogrel are inhibited by atorvastatin. We sought to address this issue prospectively by performing serial measurements of 19 platelet characteristics using conventional aggregometry, rapid analyzers, and flow cytometry. The Interaction of Atorvastatin and Clopidogrel Study (Interaction Study) was designed for patients undergoing coronary stenting. All patients (n = 75) received 325 mg of aspirin daily for at least 1 week and 300 mg of clopidogrel immediately prior to stent implantation. They had been taking atorvastatin (n = 25), any other statin (n = 25), or no statin (n = 25) for at least 30 days prior to stenting. The main outcome measure was comparison of platelet biomarkers 4 and 24 hours after clopidogrel administration between study groups. At baseline, patients from both statin groups exhibited diminished platelet aggregation and reduced platelet expression of G-protein-coupled protease-activated thrombin receptor (PAR)-1. There were no significant differences in measured platelet characteristics among the study groups 4 and 24 hours after clopidogrel intake, with the exception of a lower collagen-induced aggregation at 24 hours and a constantly diminished expression of PAR-1 in patients treated with any statin. Statins in general, and atorvastatin in particular, do not affect the ability of clopidogrel to inhibit platelet function in patients undergoing coronary stenting. These prospective data also suggest that statins may inhibit platelets directly via yet unknown mechanism(s) possibly related to the regulation of the PAR-1 thrombin receptors.


An assessment of the immune costs associated with meiotic drive elements in Drosophila.
Most organisms are constantly adapting to pathogens and parasites that exploit their host for their own benefit. Less studied, but perhaps more ubiquitous, are intragenomic parasites or selfish genetic elements. These include transposable elements, selfish B chromosomes and meiotic drivers that promote their own replication without regard to fitness effects on hosts. Therefore, intragenomic parasites are also a constant evolutionary pressure on hosts. Gamete-killing meiotic drive elements are often associated with large chromosomal inversions that reduce recombination between the drive and wild-type chromosomes. This reduced recombination is thought to reduce the efficacy of selection on the drive chromosome and allow for the accumulation of deleterious mutations. We tested whether gamete-killing meiotic drive chromosomes were associated with reduced immune defence against two bacterial pathogens in three species of Drosophila. We found little evidence of reduced immune defence in lines with meiotic drive. One line carrying the Drosophila melanogaster autosomal Segregation Distorter did show reduced defence, but we were unable to attribute that reduced defence to either genotype or immune gene expression differences. Our results suggest that though gamete-killing meiotic drive chromosomes probably accumulate deleterious mutations, those mutations do not result in reduced capacity for immune defence.


An ironman triathlon does not lead to a change in body mass in female triathletes.
In 16 female nonprofessional Ironman triathletes, body mass, percent body fat, and skeletal muscle mass were determined before and after an Ironman race in order to detect changes. Selected hematological and urinary variables as well as percent total body water were measured in order to quantify a change in hydration status. Body mass, skeletal muscle mass, percent body fat, and percent body water did not change (p > 0.05). Plasma volume increased significantly by 8.1 (13.7) % (p < 0.05). The significant increase in plasma volume, plasma urea concentration, and urinary specific gravity after the race was associated with a significant fall in hematocrit and plasma sodium concentration (p < 0.05). In contrast to studies of male Ironman triathletes, we could not detect a decrease in body mass in female Ironman triathletes. The statistically insignificant loss of 0.6 kg in body mass was smaller than reported in studies of male athletes.


miRNAs in brain development.
MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development.


Use of a preferred provider plan by employees of the City of Seattle.
Little is known about the use of services in a preferred provider organization (PPO). We studied a preferred provider arrangement between Pacific Medical Center and employees of the City of Seattle. In the second 12 months of this program 8,529 subjects submitted at least one claim; of these, only 420 (4.9%) ever used the preferred provider. Those who used the PPO at least once differed significantly from those who never used it on age, sex, employee/dependent status, and utilization in the previous year. Outpatient and total charges were higher for PPO users than for nonusers before and after control for those characteristics. Those who used the PPO exclusively were similar to those who never used it. People who used both the PPO and other providers were at higher risk for use of services, and had much higher overall utilization, with or without control for other variables. No differences were found between people who obtained only a small proportion of their services at the PPO and those who had most (but not all) of their use at the PPO. Many of these findings can be explained by a self-selection model. It is important for research on PPOs to have an independent manner of assessing who is a PPO user.


Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway.
Transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) have opposite effects on diverse cellular functions, but the basis for this antagonism is not known. TGF-beta signals through a receptor serine kinase that phosphorylates and activates the transcription factors Smads 2 and 3, whereas the IFN-gamma receptor and its associated protein tyrosine kinase Jak1 mediate phosphorylation and activation of the transcription factor Stat1. Here we present a basis for the integration of TGF-beta and IFN-gamma signals. IFN-gamma inhibits the TGF beta-induced phosphorylation of Smad3 and its attendant events, namely, the association of Smad3 with Smad4, the accumulation of Smad3 in the nucleus, and the activation of TGFbeta-responsive genes. Acting through Jak1 and Stat1, IFN-gamma induces the expression of Smad7, an antagonistic SMAD, which prevents the interaction of Smad3 with the TGF-beta receptor. The results indicate a mechanism of transmodulation between the STAT and SMAD signal-transduction pathways.


Practical approach to clinical controversies in glycemic control for hospitalized surgical patients.
The importance of glycemic management in surgical patient populations stems from an association between hyperglycemia and increased rates of surgical site infections, sepsis, and mortality. Various guidelines provide recommendations regarding target glucose concentrations, but all stress the importance of avoiding hypoglycemia as well. Within the surgical patient population, glycemic targets may vary further depending on the surgical service, such as cardiac surgery, neurosurgery, or reconstructive burn surgery. Glycemic management in critically ill surgical patients is achieved primarily through the use of intravenous insulin infusion protocols. These protocols can include fixed protocols, multiplication factor protocols, and computerized algorithms. In contrast, noncritically ill surgical patients are generally managed through the utilization of subcutaneous insulin with a combination of basal, bolus, and sliding scale insulin. Insulin protocols should be effective at maintaining glucose concentrations within the specified target range with minimal hypoglycemic events. Monitoring glucose concentrations while on either an intravenous or subcutaneous insulin protocol is essential. Point-of-care testing is the primary method for monitoring glucose concentrations in both critically ill and noncritically ill surgical patients and allows for adjustment of the insulin regimen. As patients move between units and to the outpatient setting, ensuring adequate follow-up is essential to maintaining control of hyperglycemia.


Biogeography and adaptation in the Kuril Islands, Northeast Asia.
The Circumpolar North is generally recognized as a challenging environment to inhabit and yet, we know relatively little about how people managed their welfare in these places. Here, we add to the understanding of maritime hunter-gatherers in the subarctic North Pacific through a comparative approach that synthesizes biogeographic and archaeological data from the Kuril Islands. We conclude that our faunal, ceramic and lithic evidence support expectations from biogeography as assemblages from low biodiversity and insular regions show limited diet breadth, more locally produced pottery and a conservation of lithic resources. However, we highlight that these ecological factors did not strictly determine the occupation history of the archipelago as radiocarbon data suggests all regions experienced similar demographic fluctuations regard-less of their biogeography. These results imply additional pressures influenced the strategic use and settlement of the Kuril Islands and the need for increased chronological resolution to disentangle these complex historical factors.


Phosphorylation of paxillin at threonine 538 by PKCdelta regulates LFA1-mediated adhesion of lymphoid cells.
We investigated the PKCdelta-mediated phosphorylation of paxillin within its LIM4 domain and the involvement of this phosphorylation in activation of LFA-1 integrins of the Baf3 pro-B lymphocytic cell line. Using phosphorylated-threonine-specific antibodies, phosphorylated amino acid analysis and paxillin phosphorylation mutants, we demonstrated that TPA, the pharmacological analog of the endogenous second messenger diacyl glycerol, stimulates paxillin phosphorylation at threonine 538 (T538). The TPA-responsive PKC isoform PKCdelta directly binds paxillin in a yeast two-hybrid assay and phosphorylates paxillin at T538 in vitro and also co-immunoprecipitates with paxillin and mediates phosphorylation of this residue in vivo. Recombinant wild-type paxillin, its phospho-inhibitory T538A or phospho-mimetic T538E mutants were expressed in the cells simultaneously with siRNA silencing of the endogenous paxillin. These experiments suggest that phosphorylation of paxillin T538 contributes to dissolution of the actin cytoskeleton, redistribution of LFA-1 integrins and an increase in their affinity. We also show that phosphorylation of T538 is involved in the activation of LFA-1 integrins by TPA.


Modeling the growth of Salmonella in cut red round tomatoes as a function of temperature.
Tomato-associated Salmonella outbreaks have recently become a significant food safety concern. Temperature abuse of cut tomatoes may have played a role in some of these outbreaks. The purpose of this study was to develop a mathematical model to describe the growth of Salmonella on cut tomatoes at various temperatures. Four Salmonella serotypes (Typhimurium, Newport, Javiana, and Braenderup) obtained from previous tomato-linked cases of salmonellosis were used in this study. These four serotypes were cultured separately, combined into a cocktail, and inoculated onto whole red round tomatoes and allowed to dry overnight. The tomatoes were then cut into pieces and incubated at a predetermined range of temperatures (10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, and 35 degrees C). Salmonella concentration was measured at specified time intervals to determine the growth curve for Salmonella on cut tomatoes at each temperature. The growth rates were calculated using DMFit and used to build a mathematical model to illustrate the relationship between the growth rates of Salmonella on tomatoes and incubation temperatures from 10 to 35 degrees C. The resulting model compared favorably with a Salmonella growth model for raw poultry developed by our laboratory. The Pathogen Modeling Program underpredicted growth at low temperatures and overpredicted growth at high temperatures. ComBase predicted consistently slower growth rates than were observed in tomatoes but showed parallel increases in growth rate with increasing temperature.


Medullary Sponge Kidney: Current Perspectives.
Medullary Sponge Kidney (MSK) disease is a rare congenital malformation of the distal nephron where cystic dilatation is appreciable in the collecting ducts and renal papillae. Most cases of the malformation are thought to arise from a malfunction within neurotrophic factor and tyrosine kinase interactions. Presentation and prognosis are usually indolent; however, they include urinary tract infections (UTI), nephrolithiasis and nephrocalcinosis, distal renal tubular acidosis (dRTA) and hypocitraturia. With an insidious and asymptomatic onset, MSK is a difficult renal manifestation to both diagnose and treat. Difficulty diagnosing MSK today arises from clinical settings deviating from the usage of contrast methods when assessing the urogenital tract. Many healthcare standards for kidney disorders center diagnosis around imaging techniques rather than contrast methods. This ultimately leads to a decrease in the total number of confirmed cases of MSK. Though intra-venous urogram (IVU) remains as the current gold standard to diagnose MSK, other methods such as endoscopy and Multi-detector computed tomography (MDCT) are being put into place. Endoscopic examination and renal biopsy may allow definitive diagnosis; however, such invasive methods may be considered excessive. Moving forward, differential diagnoses for MSK can be made more precisely when patients present with other renal manifestations, especially in groups at risk. These groups include patients between the age of 20 and 30, patients with other renal malformations, high sodium diet patients, hyperparathyroid patients, and patients with family history of MSK. Basic treatment is aimed at controlling stone formation by stabilizing urinary pH. Treatment for patients, especially those prone to forming stones, includes the application of potassium citrate compounds, prophylactic water and diet control, surgical intervention or lithotripsy for removal of symptomatic kidney stones.


Metatarsophalangeal joint extension changes ultrasound measurements for plantar fascia thickness.
Ultrasound is an inexpensive method for quantifying plantar fascia thickness, especially in those with plantar fasciitis. Ultrasound has also been used to assess the effectiveness of various treatments for plantar fasciitis by comparing plantar fascia thickness before and after an intervention period. While a plantar fascia thickness over 4 mm via ultrasound has been proposed to be consistent with plantar fasciitis, some researchers believe the 4 mm plantar fascia thickness level to be a dubious guideline for diagnosing plantar fasciitis due to the lack of standardization of the measurement process for plantar fascia thickness. In particular, no universal guidelines exist on the positioning of the metatarsophalangeal (MTP) joints during the procedure and the literature also has inconsistent protocols. The purpose of this study is to investigate and compare the influence of MTP joint extension on plantar fascia thickness in healthy participants and those with unilateral plantar fasciitis. The plantar fascia thickness of forty participants (20 with unilateral plantar fasciitis and 20 control) was measured via ultrasound three times at three different MTP joint positions: 1) at rest, 2) 30° of extension from the plantar surface, and 3) maximal extension possible. The plantar fascia became significantly thinner as MTP joint extension increased in both the plantar fasciitis group (p < 0.001) and the control group (p < 0.001). In the plantar fasciitis group, the involved plantar fascia was 1.2 to 1.3 mm thicker (p < 0.001) than the uninvolved side depending on the MTP joint position. In the control group, the difference in plantar fascia thickness between the two sides was less than 0.1 mm (p < 0.92) at any MTP joint position. MTP joint position can influence the ultrasound measurement of plantar fascia thickness. It is recommended that plantar fascia thickness measurements be performed with the toes at rest. If MTP joints must be extended, then the toes should be extended maximally and then noted to ensure subsequent ultrasound procedures are repeated. Standardizing the position of the MTP joints is not only important for attaining the most accurate thickness measurement of the plantar fascia, but is also important to researchers who use plantar fascia thickness to determine the effectiveness of various plantar fasciitis interventions.


Early versus late initiation of epidural analgesia for labour.
Pain during childbirth is arguably the most severe pain some women may experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour. Many women have concerns regarding its safety. Furthermore, epidural services and anaesthetic support may not be available consistently across all centres. Observational data suggest that early initiation of epidural may be associated with an increased risk of caesarean section, but the same findings were not seen in recent randomised controlled trials. More recent guidelines suggest that in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labour. The choice of analgesic technique, agent, and dosage is based on many factors, including patient preference, medical status, and contraindications. There is no systematically reviewed evidence on the maternal and foetal outcomes and safety of this practice. This systematic review aimed to summarise the effectiveness and safety of early initiation versus late initiation of epidural analgesia in women. We considered the obstetric and fetal outcomes relevant to women and side effects of the treatments, including risk of caesarean section, instrumental birth and time to birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 February 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1966 to February 2014), Embase (January 1980 to February 2014) and reference lists of retrieved studies. We included all randomised controlled trials involving women undergoing epidural labour analgesia that compared early initiation versus late initiation of epidural labour analgesia. Two review authors independently assessed trials for inclusion, extracted the data and assessed the trial quality. Data were checked for accuracy. We included nine studies with a total of 15,752 women.The overall risk of bias of the studies was low, with the exception of performance bias (blinding of participants and personnel).The nine studies showed no clinically meaningful difference in risk of caesarean section with early initiation versus late initiation of epidural analgesia for labour (risk ratio (RR) 1.02; 95% confidence interval (CI) 0.96 to 1.08, nine studies, 15,499 women, high quality evidence). There was no clinically meaningful difference in risk of instrumental birth with early initiation versus late initiation of epidural analgesia for labour (RR 0.93; 95% CI 0.86 to 1.01, eight studies, 15,379 women, high quality evidence). The duration of second stage of labour showed no clinically meaningful difference between early initiation and late initiation of epidural analgesia (mean difference (MD) -3.22 minutes; 95% CI -6.71 to 0.27, eight studies, 14,982 women, high quality evidence). There was significant heterogeneity in the duration of first stage of labour and the data were not pooled.There was no clinically meaningful difference in Apgar scores less than seven at one minute (RR 0.96; 95% CI 0.84 to 1.10, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in Apgar scores less than seven at five minutes (RR 0.96; 95% CI 0.69 to 1.33, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in umbilical arterial pH between early initiation and late initiation (MD 0.01; 95% CI -0.01 to 0.03, four studies, 14,004 women, high quality evidence). There was no clinically meaningful difference in umbilical venous pH favouring early initiation (MD 0.01; 95% CI -0.00 to 0.02, four studies, 14,004 women, moderate quality evidence). There is predominantly high-quality evidence that early or late initiation of epidural analgesia for labour have similar effects on all measured outcomes. However, various forms of alternative pain relief were given to women who were allocated to delayed epidurals to cover that period of delay, so that is it hard to assess the outcomes clearly. We conclude that for first time mothers in labour who request epidurals for pain relief, it would appear that the time to initiate epidural analgesia is dependent upon women's requests.


Pressure-Induced Metallization of BaH2 and the Effect of Hydrogenation.
Using optical spectroscopy, X-ray diffraction, and electrical transport measurements, we have studied the pressure-induced metallization in BaH2 and Ba8H46. Our combined measurements suggest a structural phase transition from BaH2-II to BaH2-III accompanied by band gap closure and transformation to a metallic state at 57 GPa. The metallization is confirmed by resistance measurements as a function of the pressure and temperature. We also confirm that, with further hydrogenation, BaH2 forms the previously observed Weaire-Phelan Ba8H46, synthesized at 45 GPa and 1200 K. In this compound, metallization pressure is shifted to 85 GPa. Through a comparison of the properties of these two compounds, a question is raised about the importance of the hydrogen content in the electronic properties of hydride systems.


Identification of glutamate receptors and transporters in mouse and human sperm.
gamma-Aminobutyric acid (GABA) and glutamate (Glu) are considered as the predominant inhibitory and excitatory neurotransmitters in mammalian central nervous systems (CNS), respectively. The presence of the GABA system and metabotropic glutamate receptors in sperm prompted us to explore the existence of ionotropic glutamate receptors and glutamate transporters in sperm. Immunofluorescent analysis was used to investigate the existence and location of glutamate, glutamate receptor (NR2B), and glutamate transporter (GLT1) in mouse and human sperm. Our present results showed that NR2B was located in the midpiece of sperm, whereas GLT1 mainly existed in the head. Moreover, glutamate uptake activity was detected in mouse sperm and it could be blocked by dihydrokainic acid (DHK, GLT1-selective inhibitor) and DL-threo-beta-hydroxyaspartic acid (THA, nonselective inhibitor). In addition, reverse transcription-polymerase chain reaction technique and sequencing analysis revealed that glutamate transporters (GLT1 and EAAC1) and ionotropic glutamate receptors (NR1, NR2B, GluR6, and KA2) existed in mouse sperm as well as in human sperm. The present findings are the first direct evidence for the existence of ionotropic glutamate receptors and glutamate transporters in sperm. It also indicates that, in sperm, glutamate receptors and transporters might have functions other than neurotransmission.


[Diagnostic image (20). Prolapsed submucous fibromyoma].
In a 48-year-old woman suffering from acute strong pain in the lower abdomen spontaneous partial delivery of a submucous fibromyoma was diagnosed.


The regulation of 1-aminocyclopropane-1-carboxylic acid synthase gene expression during the transition from system-1 to system-2 ethylene synthesis in tomato.
1-Aminocyclopropane-1-carboxylic acid synthase (ACS) is one of the key regulatory enzymes involved in the synthesis of the hormone ethylene and is encoded by a multigene family containing at least eight members in tomato (Lycopersicon esculentum). Increased ethylene production accompanies ripening in tomato, and this coincides with a change in the regulation of ethylene synthesis from auto-inhibitory to autostimulatory. The signaling pathways that operate to bring about this transition from so-called system-1 to system-2 ethylene production are unknown, and we have begun to address these by investigating the regulation of ACS expression during ripening. Transcripts corresponding to four ACS genes, LEACS1A, LEACS2, LEACS4, and LEACS6, were detected in tomato fruit, and expression analysis using the ripening inhibitor (rin) mutant in combination with ethylene treatments and the Never-ripe (Nr) mutant has demonstrated that each is regulated in a unique way. A proposed model suggests that system-1 ethylene is regulated by the expression of LEACS1A and LEACS6. In fruit a transition period occurs in which the RIN gene plays a pivotal role leading to increased expression of LEACS1A and induction of LEACS4. System-2 ethylene synthesis is subsequently initiated and maintained by ethylene-dependent induction of LEACS2.


Phytochemical Analysis and Antioxidant Property of Leaf Extracts of Vitex doniana and Mucuna pruriens.
Oxidative stress and impaired antioxidant system have been implicated in the pathophysiology of diverse disease states. The phytochemical screening and antioxidant property of fresh leaves of Vitex doniana and Mucuna pruriens, used in the management and treatment of various diseases, were studied. The extracts (ethanol and distilled water) were screened for the presence of phytochemicals, and their inhibition of 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical was used to evaluate their free radical scavenging activity. Liver levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in carbon tetrachloride- (CCl(4)) treated albino rats were also used to assess the antioxidant activity of the extracts. The animals were treated with 250 mg/kg body weight of the extracts for six consecutive days before a single dose (2.5 mL/kg body weight) of CCl(4). Vitamin C was used as the standard antioxidant. Phytochemical screening revealed the presence of saponins, tannins, anthraquinones, terpenoids, and flavonoids in all the extracts, while alkaloids were detected in extracts of Vitex doniana only, and cardiac glycosides occurred in extracts of Mucuna pruriens only. All the extracts inhibited DPPH radical in a concentration-dependent manner, water extract of Vitex doniana producing highest inhibition which was not significantly different (P > .05) from vitamin C. The extracts produced a significant decrease (P < .05) in liver MDA, while the levels of SOD and CAT significantly increased (P < .05) relative to the positive control. These results are an indication of antioxidant potential of the extracts and may be responsible for some of the therapeutic uses of these plants.


Adequate lymphadenectomy for colorectal cancer: a comparative analysis between open and laparoscopic surgery.
In the surgical treatment of colorectal cancer, a lymphadenectomy is considered adequate when at least 12 lymph nodes are removed. To evaluate whether videolaparoscopic surgery positively affects the rates of adequate lymphadenectomy. An observational study was conducted with patients undergoing either open or videolaparoscopic surgery for colorectal cancer between 2008 and 2013. The following variables were collected: gender, age, tumor site, histology, degree of differentiation, tumor stage, number of lymph nodes removed, and number of lymph nodes affected by the disease. A total of 62 patients with colorectal cancer were included; 42 (67.7%) received open surgery, and 20 (32.3%) laparoscopic surgery. Regarding lymphadenectomy, a mean of 13 lymph nodes (95% CI: 10-16) were removed in the group that received open surgery, while 19 lymph nodes were removed (95% CI: 14-24) in the laparoscopic surgery group (p=0.021). Adequate lymphadenectomy (removal of at least 12 lymph nodes) was achieved in 58.1% of the total cases, in 50.0% of the patients who received open surgery, and in 75% of those who received laparoscopic surgery. Non-elderly patients and those with an advanced disease stage were more likely to receive an adequate lymphadenectomy (p=0.004 and p=0.035, respectively). Disease stage and patient age were the factors that had the greatest influence on achieving an adequate lymphadenectomy. The type of surgery did not affect the number of lymph nodes removed.


Executive functions in adult offspring of alcohol-dependent probands: toward a cognitive endophenotype?
Executive function (EF) impairment in alcohol dependence (AD) has been related to the toxic effects of alcohol on frontal lobes. However, this impairment could be partially present before the onset of the disease and might constitute a vulnerability factor. Although a considerable body of research has investigated executive functioning among AD patients, much less attention has been directed toward high-risk individuals. Most studies were carried out among children or adolescents, and very few were conducted in adults. The aim of this study was to examine EF in a group of adult offspring of AD individuals. One hundred and fifty-five nonalcoholic adults with (family history positive [FHP]) or without (family history negative [FHN]) family history of AD were included in the study. All participants were screened for past and current psychiatric diagnoses, and alcohol, tobacco, and other substance use. They were compared on self-rated impulsiveness using the Barratt Impulsiveness Scale-11 (BIS-11) and EF using a neuropsychological test battery. Group comparison revealed that FHP participants had significantly higher BIS-11 scores than the FHN participants, while neuropsychological examination revealed lower EF scores for FHP participants. Hierarchical regression analysis revealed that the number of AD family members was a predictor of EF results, whereas impulsiveness was not. Nonalcoholic adult offspring of AD individuals showed increased impulsiveness and decreased EF, suggesting weakness of 2 distinct neurobehavioral decision systems. Findings support evidence that EF weaknesses may qualify as a suitable endophenotype candidate for AD.


The Role of Governments in the Implementation of Patient Safety and Patient Safety Incident Reporting in Indonesia: A Qualitative Study.
(1) Background: A patient safety incident reporting system was introduced in Indonesian hospitals in 2006; however, under-reporting of patient safety incidents is evident. The government plays a vital role in the implementation of a national system. Therefore, this study focuses on how the Indonesian government has been undertaking its role in patient safety at provincial and city/district levels, including incident reporting according to the National Guideline for Hospital Patient Safety. (2) Methods: This study employed a qualitative approach with interviews of 16 participants from seven organizations. The data were managed using NVivo and thematically analyzed. (3) Results: The findings revealed several problems at the macro-, meso-, and micro-level as the government was weak in monitoring and evaluation. The District Health Office (DHO) and Provincial Health Office (PHO) were not involved in incident reporting, and there was a lack of government support for the hospitals. (4) Conclusions: The DHO and PHO have not carried out their roles related to patient safety as mentioned in the national guidelines. Lack of commitment to and priority of patient safety, the complexity of the bureaucratic structure, and a lack of systematic partnership and collaboration are problems that need to be addressed by systematic improvement. To ensure effective and efficient national outcomes, the three levels of government need to work more closely.


Role of coronary artery surgery in patients surviving unexpected cardiac arrest.
During the past 3-1/2 years, 101 of 199 patients who were successfully resuscitated by fire rescue squads in the community after unexpected cardiac arrest (documented ventricular fibrillation--VF) were admitted to the hospital. Forty-two of these patients ultimately were discharged from the hospital. However, the intermediate and long-term results were disappointing, for their mean survival after discharge was only 12.7 months. Sudden deaths (recurrent unexpected VF) occurred during the first 12 months after discharge in 28 percent of the patients surviving the initial hospitalization. Among the survivors of sudden and unexpected VF (i.e., survivors of the initial hospitalization), 16 patients who had had pre-existing symptoms of coronary heart disease had hemodynamic and coronary angiographic studies. Of these, 11 were considered surgical candidates. This report concerns the follow-up results in these patients with particular emphasis on the eight patients who accepted surgery and had myocardial revascularization. Five patients had moderate hemodynamic abnormalities, but none had had an acute myocardial infarction at the time of the initial arrest. The group of eight patients had a total of 18 vein graft bypasses performed. The significant findings is that all eight survived operation, and there was one late death at 10 months. The remaining patients are alive at 14 to 34 months, and six are free of symptoms. Despite patent vein grafts, one patient has had a second serious arrhythmia. It is concluded that surgical intervention can be done safely and may decrease the high posthospitalization, recurrent arrest, and mortality rates in selected survivors of unexpected cardiac arrest. It is concluded further that all patients sustaining an unexpected arrest should have postarrest coronary catheterization and angiography, and all patients should be on antiarrhythmic agents whether or not they receive myocardial revascularization.


The process of quality management.
Hospitals are focusing their attention on quality improvement programs to meet the demands of the health care consumer. Managers need to be educated in the methodology and process of total quality management (TQM).


Evaluating the diagnostic utility of applying a machine learning algorithm to diffusion tensor MRI measures in individuals with major depressive disorder.
Using MRI to diagnose mental disorders has been a long-term goal. Despite this, the vast majority of prior neuroimaging work has been descriptive rather than predictive. The current study applies support vector machine (SVM) learning to MRI measures of brain white matter to classify adults with Major Depressive Disorder (MDD) and healthy controls. In a precisely matched group of individuals with MDD (n =25) and healthy controls (n =25), SVM learning accurately (74%) classified patients and controls across a brain map of white matter fractional anisotropy values (FA). The study revealed three main findings: 1) SVM applied to DTI derived FA maps can accurately classify MDD vs. healthy controls; 2) prediction is strongest when only right hemisphere white matter is examined; and 3) removing FA values from a region identified by univariate contrast as significantly different between MDD and healthy controls does not change the SVM accuracy. These results indicate that SVM learning applied to neuroimaging data can classify the presence versus absence of MDD and that predictive information is distributed across brain networks rather than being highly localized. Finally, MDD group differences revealed through typical univariate contrasts do not necessarily reveal patterns that provide accurate predictive information.


The RhoGEF trio functions in sculpting class specific dendrite morphogenesis in Drosophila sensory neurons.
As the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures. Here we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da) sensory neurons of the Drosophila peripheral nervous system (PNS). Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis. Collectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia formation.


Creation of matrix protein gene variants of two serotypes of vesicular stomatitis virus as prime-boost vaccine vectors.
To take advantage of live recombinant vesicular stomatitis viruses (rVSVs) as vaccine vectors for their high yield and for their induction of strong and long-lasting immune responses, it is necessary to make live vaccine vectors safe for use without losing their immunogenicity. We have generated safer and highly efficient recombinant VSV vaccine vectors by combining the M51R mutation in the M gene of serotype VSV-Indiana (VSVInd) with a temperature-sensitive mutation (tsO23) of the VSVInd Orsay strain. In addition, we have generated two new serotype VSV-New Jersey (VSVNJ) vaccine vectors by combining M48R and M51R mutations with G22E and L110F mutations in the M gene, rVSVNJ(G22E M48R M51R) [rVSVNJ(GMM)] and VSVNJ(G22E M48R M51R L110F) [rVSVNJ(GMML)]. The combined mutations G21E, M51R, and L111F in the M protein of VSVInd significantly reduced the burst size of the virus by up to 10,000-fold at 37°C without affecting the level of protein expression. BHK21 cells and SH-SY5Y human neuroblastoma cells infected with rVSVInd(GML), rVSVNJ(GMM), and rVSVNJ(GMML) showed significantly reduced cytopathic effects in vitro at 37°C, and mice injected with 1 million infectious virus particles of these mutants into the brain showed no neurological dysfunctions or any other adverse effects. In order to increase the stability of the temperature-sensitive mutant, we have replaced the phenylalanine with alanine. This will change all three nucleotides from UUG (leucine) to GCA (alanine). The resulting L111A mutant showed the temperature-sensitive phenotype of rVSVInd(GML) and increased stability. Twenty consecutive passages of rVSVInd(GML) with an L111A mutation did not convert back to leucine (UUG) at position 111 in the M protein gene. Recombinant vesicular stomatitis viruses as live vaccine vectors are very effective in expressing foreign genes and inducing adaptive T cell and B cell immune responses. As with any other live viruses in humans or animals, the use of live rVSVs as vaccine vectors demands the utmost safety. Our strategy to attenuate rVSVInd by utilizing a temperature-sensitive assembly-defective mutation of L111A and combining it with an M51R mutation in the M protein of rVSVInd significantly reduced the pathogenicity of the virus while maintaining highly effective virus production. We believe our new temperature-sensitive M gene mutant of rVSVInd(GML) and M gene mutants of rVSVNJ(GMM) and rVSVNJ(GMML) add excellent vaccine vectors to the pool of live viral vectors.


Prevalence of and risk factors for diabetes mellitus in the school-attending adolescent population of the United Arab Emirates: a large cross-sectional study.
The prevalence of diabetes has reportedly increased among adolescents in low-income and middle-income countries of the Middle East and may be linked to social, demographic and economic contextual factors. This study aimed: (1) to estimate the prevalence of self-reported diagnosis of diabetes in the adolescent population of the United Arab Emirates (UAE); (2) to assess differences in the prevalence based on gender and (3) to identify other characteristics of those with diabetes including parental marital status, smoking/illegal drug use, quality of life and nationality. A secondary data analysis was performed on data from the National Study of Population Health in the UAE, conducted between 2007 and 2009. Large cross-sectional population-based survey study. Survey was administered to a stratified random sample of 151 public and private schools from the UAE, across 7 emirates. 6365 school-attending adolescents (12-22 years; mean=16 years) participated. Multivariable logistic regression analysis was used to examine the relationships between diabetes diagnosis and characteristics of participants after adjusting for confounding from other predictors. The overall prevalence of self-reported diabetes was 0.9% (95% CI 0.7% to 1.2%) and was higher in males 1.5% (95% CI 1.0% to 2.1%) than females 0.5% (95% CI 0.3% to 0.8%), (p<0.001). Children of parents who were not currently married had more than twice the odds of self-reporting diabetes (p=0.031) compared with those with married parents. Adolescents who reported ever smoking/using illegal drugs had more than three times the odds of diabetes (p<0.001). We found a positive association between certain characteristics of adolescents and their diabetes status, including male gender, parental marital status and smoking/illegal drug use. The high prevalence of smoking/illegal drug use among those reporting a diagnosis of diabetes suggests the need for behavioural and mental health interventions for adolescents with diabetes, as well as strong parental support and involvement.


Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization.
The presence of anti-HLA antibodies is an increasing challenge in kidney transplantation. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), has been proposed to complement conventional desensitization therapy. We aimed to describe TCZ plasma trough concentrations and their variability and to investigate the link between TCZ concentration and the evolution of anti-HLA antibodies. Sensitized kidney-transplant candidates treated monthly with TCZ (8 mg/kg) for desensitization were retrospectively included. TCZ concentrations were determined by liquid chromatography-tandem mass spectrometry. Seventy-four TCZ concentrations from 10 patients were analyzed. The TCZ trough concentration ranged from <1.0 to 52.5 mg·L-1, with a median of 25.6 mg·L-1 [25th-75th percentiles: 13.2-35.3 mg·L-1). The inter- and intra-individual coefficients of variation were 55.0% and 33.0%, respectively. The TCZ trough concentration was not related to IL-6 (rho = -0.46, p = 0.792), soluble IL-6R (rho = -0.81, p = 0.65) concentrations or reduction of anti-HLA antibodies (mixed-effects model adjusting, effect of TCZ trough concentration: rho = -0.004, p = 0.26). The individual median TCZ concentration tended to be associated with the number of antibodies, with an initial MFI > 3000 that dropped to <3000 after TCZ treatment (rho = 0.397, p = 0.083). TCZ trough concentrations in kidney-transplant candidates treated for desensitization were highly variable. Further studies on larger cohorts are needed to study the possible link between TCZ concentrations and the reduction of anti-HLA antibodies.


How adults understand what young children say.
Children's early speech often bears little resemblance to that of adults, and yet parents and other caregivers are able to interpret that speech and react accordingly. Here we investigate how adult listeners' inferences reflect sophisticated beliefs about what children are trying to communicate, as well as how children are likely to pronounce words. Using a Bayesian framework for modelling spoken word recognition, we find that computational models can replicate adult interpretations of children's speech only when they include strong, context-specific prior expectations about the messages that children will want to communicate. This points to a critical role of adult cognitive processes in supporting early communication and reveals how children can actively prompt adults to take actions on their behalf even when they have only a nascent understanding of the adult language. We discuss the wide-ranging implications of the powerful listening capabilities of adults for theories of first language acquisition.


Typing of chronic obstructive pulmonary disease using high-resolution computed tomography and the association with smoking, airway inflammation, and common comorbidities
Background/aim: This study performed typing of chronic obstructive pulmonary disease (COPD) using high-resolution computed tomography (HRCT) to determine the association with smoking, matrix metalloproteinases, and common comorbidities. Materials and methods: The study enrolled 94 hospitalized patients. Participants were divided into a group of 69 current and former smokers (group A) and a group of 25 that had never smoked (group B). Patients were also divided into 3 categories according to the degree of emphysema and bronchial wall thickness using HRCT to determine the association with levels of matrix metalloproteinase 9 (MMP-9) and TIMP-1, as well as associated comorbidities. These three categories were: type A - no or mild emphysema, with or without bronchial wall thickening; type E - emphysema without bronchial wall thickening; and type M - both emphysema and bronchial wall thickening. Results: The low attenuation area (LAA) scores in group A patients were higher than those in group B (t = 2.86, P < 0.01); correlation analysis showed that smoking was associated with a decline of the forced expiratory volume in 1 s and forced vital capacity ratio (FEV1/ FVC%) and higher LAA scores in patients with COPD (F = 4.46, F = 8.20, P < 0.05). The levels of MMP-9 in group A were higher than those in group B (t = 3.65, P < 0.01). Among COPD patients with more than 3 comorbidities, there were statistically significant differences in both the smoking group and the nonsmoking group (chi-square = 12.08, P < 0.01). When compared to type A patients, who had coincident cardiovascular diseases in the smoking group, patients of type M and E showed statistically significant differences (F = 2.42 and 2.12, P < 0.05). Conclusion: Emphysema was more severe in smokers. Metalloproteinase levels in smokers were higher than those in nonsmokers. Moreover, comorbidities were more severe in smokers.


Effects of the peroxisome proliferator-activated receptor-alpha agonists clofibrate and fish oil on hepatic fatty acid metabolism in weaned dairy calves.
Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists increase fatty acid oxidation in liver of nonruminants. If similar effects occur in dairy cattle, enhanced hepatic oxidative capacity could decrease circulating nonesterified fatty acids and hepatic triacylglycerol accumulation in periparturient cows. The objectives of this study were 1) to determine whether partitioning of fatty acid metabolism by liver slices from weaned Holstein calves treated with PPARalpha agonists in vivo is altered compared with partitioning by liver slices from control (untreated) calves, and 2) to measure in vitro metabolism of palmitate and oleate by bovine liver slices and relate these to mRNA abundance for key enzymes. Weaned male Holstein calves (7 wk old; n=15) were assigned to 1 of 3 groups for a 5-d treatment period: control (untreated), clofibrate (62.5 mg/kg of BW), or fish oil (250 mg/kg of BW). Calves treated with clofibrate consumed less dry matter. Body weight, liver weight, liver weight:body weight ratio, blood nonesterified fatty acids, beta-hydroxybutyrate, and liver composition were not significantly different among treatments. Liver slices were incubated for 2, 4, and 8 h to determine in vitro conversion of [1-(14)C] palmitate and [1-(14)C] oleate to CO(2), acid-soluble products, esterified products, and total metabolism. In liver slices incubated for 8 h, conversion of palmitate to CO(2) was greater for calves treated with clofibrate compared with control calves or calves treated with fish oil. Conversion of palmitate to esterified products, total palmitate metabolism, and metabolism of oleate were not different among treatments. Conversion of palmitate to CO(2) was greater than that from oleate for all treatments, but rates of total metabolism did not differ. Clofibrate increased or tended to increase liver expression of several PPARalpha target genes involved in fatty acid oxidation (e.g., ACADVL, ACOX1, CPT1A), whereas fish oil did not significantly affect genes associated with fatty acid oxidation but tended to increase DGAT1. Overall, our data indicated that bovine liver responded to clofibrate treatment but not fish oil, although increases in hepatic lipid metabolism were much less than those reported in rodents treated with clofibrate or fish oil. Applications of PPARalpha agonists may be of interest to increase the rate of hepatic fatty acid oxidation and decrease triacylglycerol accumulation in periparturient dairy cows.


Hazard Ranking Methodology for Assessing Health Impacts of Unconventional Natural Gas Development and Production: The Maryland Case Study.
The recent growth of unconventional natural gas development and production (UNGDP) has outpaced research on the potential health impacts associated with the process. The Maryland Marcellus Shale Public Health Study was conducted to inform the Maryland Marcellus Shale Safe Drilling Initiative Advisory Commission, State legislators and the Governor about potential public health impacts associated with UNGDP so they could make an informed decision that considers the health and well-being of Marylanders. In this paper, we describe an impact assessment and hazard ranking methodology we used to assess the potential public health impacts for eight hazards associated with the UNGDP process. The hazard ranking included seven metrics: 1) presence of vulnerable populations (e.g. children under the age of 5, individuals over the age of 65, surface owners), 2) duration of exposure, 3) frequency of exposure, 4) likelihood of health effects, 5) magnitude/severity of health effects, 6) geographic extent, and 7) effectiveness of setbacks. Overall public health concern was determined by a color-coded ranking system (low, moderately high, and high) that was generated based on the overall sum of the scores for each hazard. We provide three illustrative examples of applying our methodology for air quality and health care infrastructure which were ranked as high concern and for water quality which was ranked moderately high concern. The hazard ranking was a valuable tool that allowed us to systematically evaluate each of the hazards and provide recommendations to minimize the hazards.


The extent and frequency of abuse in the lives of older women and their relationship with health outcomes.
This study assessed the extent of different types of abuse, repeated and multiple abuse experiences among women aged 60 and older, and their effects on the women's self-reported health. A cross-sectional study of a clinical sample of 842 community-dwelling women aged 60 and older completed a telephone survey about type and frequency of abuse, self-reported health status and health conditions, and demographic characteristics. Bivariate and multivariate analyses were performed using SPSS 11.5 and STATA 7.0. Nearly half of the women had experienced at least one type of abuse--psychological/emotional, control, threat, physical, or sexual--since turning 55 years old. Sizable proportions were victims of repeat abuse. Many women experienced multiple types of abuse and experienced abuse often. Abused older women were significantly more likely to report more health conditions than those who were not abused. Women who experienced psychological/emotional abuse--alone, repeatedly, or with other types of abuse--had significantly increased odds of reporting bone or joint problems, digestive problems, depression or anxiety, chronic pain, and high blood pressure or heart problems. It is important that health care and service providers acknowledge psychological/emotional, control, threat, physical, and sexual abuse against older women and understand their health implications. In addition, it is important for providers to be trained in both aging and domestic violence services and resources.


Endocrine targets of hypoxia-inducible factors.
Endocrine is an important and tightly regulated system for maintaining body homeostasis. Endocrine glands produce hormones, which are released into blood stream to guide the target cells responding to all sorts of stimulations. For maintaining body homeostasis, the secretion and activity of a particular hormone needs to be adjusted in responding to environmental challenges such as changes in nutritional status or chronic stress. Hypoxia, a status caused by reduced oxygen availability or imbalance of oxygen consumption/supply in an organ or within a cell, is a stress that affects many physiological and pathological processes. Hypoxic stress in endocrine organs is especially critical because endocrine glands control body homeostasis. Local hypoxia affects not only the particular gland but also the downstream cells/organs regulated by hormones secreted from this gland. Hypoxia-inducible factors (HIFs) are transcription factors that function as master regulators of oxygen homeostasis. Recent studies report that aberrant expression of HIFs in endocrine organs may result in the development and/or progression of diseases including diabetes, endometriosis, infertility and cancers. In this article, we will review recent findings in HIF-mediated endocrine organ dysfunction and the systemic syndromes caused by these disorders.


Screening for cognitive impairment in older people attending accident and emergency using the 4-item Abbreviated Mental Test.
To determine the utility of the 4-item Abbreviated Mental Test (AMT4) for detecting cognitive impairment in accident and emergency patients aged 65 years or older. Cognitive function was assessed using the Mini Mental State Examination (MMSE), 4 and 10-point AMT and subjective judgment. Cognitive impairment was defined as an MMSE score 23/30 or less. Of 601 patients, 226 (37.6%) scored 23 or less on MMSE. Cutoffs of 3 or less for AMT4 and 7 or less for AMT had sensitivities of 80% [95% confidence interval (CI): 0.75-0.85] and 76% (95% CI: 0.69-0.81), and specificities of 88% (95% CI: 0.84-0.91) and 93% (95% CI: 0.90-0.96), respectively, for detection of cognitive impairment; subjective judgement of admitting nurse had 50.5% (95% CI: 44-57%) sensitivity and 98.6% (95% CI: 0 96-1.00%) specificity. In conclusion, the AMT4 performs as well as the 10-point AMT in screening for cognitive impairment, and will assist in the early detection of cognitive problems.


Literature-based immunization recommendations for patients requiring immunosuppressive medications for autoimmune bullous dermatoses.
Autoimmune bullous diseases, such as pemphigus, pemphigoid, and dermatitis herpetiformis, are uniquely associated with vulnerability in the mucocutaneous barrier against infection. The management of immunobullous diseases is complex and may at times require immunosuppressive medications. Iatrogenic immunosuppression may increase susceptibility to vaccine-preventable illnesses. Currently, there are no guidelines to assist the clinician treating patients with immunobullous disease regarding the delivery of various vaccinations. The aim of this review is to provide recommendations for immunization in the unique setting of immunobullous disease. Recommendations are based on careful review of the literature in other conditions requiring iatrogenic immunosuppression, as well as the most recent Centers for Disease Control and Prevention guidelines. Immunization with nonlive vaccines appears to be a safe and effective strategy for preventing infection in the particularly susceptible patient with immunobullous disease. Opportunities for live vaccine administration may become available at lower levels of immune suppression or during clinical remission when immunosuppressive regimens can be reduced. Anticipatory vaccination before the initiation of iatrogenic immunosuppression is ideal. Although immunologic response to vaccination may be suboptimal during immunosuppression, nonlive vaccination is strongly recommended for this patient population.


Neurochemical substrates of ictal behavior.
Ictal activity is associated with (a) very marked changes in energy metabolism and neurotransmitter turnover and (b) complex secondary effects on second messenger systems and the control of protein synthesis. These events both reflect the abnormal patterns of excitatory and inhibitory activity and entail further modifications of neuronal function. More refined in vivo measurements of neurochemical changes and their anatomy will be required if we are to correlate the more subtle ictal behavioral abnormalities with their underlying events.


Expiratory CT scanning in COVID-19 patients: can we add useful data?
To evaluate small airway disease in COVID-19 patients using the prevalence of air trapping (AT) and correlating it with clinical outcomes. The relationship between CT-based opacities in small blood vessels and ventilation in patients with SARS-CoV-2 pneumonia was also assessed. We retrospectively included 53 patients with positive RT-PCR results for SARS-CoV-2 between March and April of 2020. All subjects underwent HRCT scanning, including inspiratory and expiratory acquisitions. Subjects were divided into two groups based on visual identification of AT. Small blood vessel volumes were estimated by means of cross-sectional areas < 5 mm2 (BV5) derived from automated segmentation algorithms. Mixed-effect models were obtained to represent the BV5 as a function of CT-based lobar opacities and lobar ventilation. Of the 53 participants, AT was identified in 23 (43.4%). The presence of AT was associated with increased SpO2 at admission (OR = 1.25; 95% CI, 1.07-1.45; p = 0.004) and reduced D-dimer levels (OR = 0.99; 95% CI, 0.99-0.99; p = 0.039). Patients with AT were less likely to be hospitalized (OR = 0.27; 95% CI, 0.08-0.89; p = 0.032). There was a significant but weak inverse correlation between BV5 and CT-based lobar opacities (R2 = 0.19; p = 0.03), as well as a nonsignificant and weak direct correlation between BV5 and lobar ventilation (R2 = 0.08; p = 0.54). AT is a common finding in patients with COVID-19 that undergo expiratory CT scanning. The presence of AT may correlate with higher SpO2 at admission, lower D-dimer levels, and fewer hospitalizations when compared with absence of AT. Also, the volume of small pulmonary vessels may negatively correlate with CT opacities but not with lobar ventilation.


Ab initio simulation of helium-ion microscopy images: the case of suspended graphene.
Helium ion microscopy (HIM), which was released in 2006 by Ward et al., provides nondestructive imaging of nanoscale objects with higher contrast than scanning electron microscopy. HIM measurement of suspended graphene under typical conditions is simulated by first-principles time-dependent density functional theory and the 30 keV He+ collision is found to induce the emission of electrons dependent on the impact point. This finding suggests the possibility of obtaining a highly accurate image of the honeycomb pattern of suspended graphene by HIM. Comparison with a simulation of He0 under the same kinetic energy shows that electron emission is governed by the impact ionization instead of Auger process initiated by neutralization of He+.


Almond processing residues as a source of organic acid biopesticides during biosolarization.
Biosolarization utilizes organic amendments to produce biopesticide compounds in soil that can work in tandem with other stresses to inactivate agricultural pests. The prospect of using by-products from industrial almond processing as amendments for biosolarization was assessed. Soil mesocosms were used to simulate biosolarization using various almond by-products, application rates, and incubation times. Several potentially biopesticidal organic acids were identified and quantified in the soil, and the toxicity of soil extracts was evaluated for the root lesion nematode (Pratylenchus vulnus). It was determined that both almond hulls and a mixture of hulls and shells harbored several acids, the concentration of which was enhanced 1-7 fold via fermentation by native soil microbes. Organic acid concentration in the soil showed a significant linear relationship with the quantity of waste biomass amended. Extracts from soils containing at least 2.5% incorporated biomass by dry weight showed a 84-100% mortality of nematodes, which corresponded to acid concentrations 0.75 mg/g (2.0 g/L) or greater. This study showed that almond processing by-products - hulls and a hull and shell mixture - were suitable amendments for control of P. vulnus and potentially other soil agricultural pests in the context of biosolarization.


Fractional Erbium laser in the treatment of photoaging: randomized comparative, clinical and histopathological study of ablative (2940nm) vs. non-ablative (1540nm) methods after 3 months.
Fractional non-ablative lasers keep the epidermis intact, while fractional ablative lasers remove it, making them theoretically more effective. To evaluate the clinical and histological alterations induced by fractional photothermolysis for treating photoaging, comparing the possible equivalence of multiple sessions of 1540nm Erbium, to one session of 2940nm Erbium. Eighteen patients (mean age 55.9) completed the treatment with three sessions of 1540nm fractional Erbium laser on one side of the face (50 mJ/mB, 15ms, 2 passes), and one session of 2940nm on the other side (5mJ/mB, 0.25ms, 2 passes). Biopsies were performed before and 3 months after treatment. Clinical, histological and morphometric evaluations were carried out. All patients presented clinical improvement with no statistically significant difference (p> 0.05) between the treated sides. Histopathology revealed a new organization of collagen and elastic fibers, accompanied by edema, which was more evident with the 2940nm laser. This finding was confirmed by morphometry, which showed a decrease in collagen density for both treatments, with a statistical significance for the 2940nm laser (p > 0.001). Three 1540nm sessions were clinically equivalent to one 2940nm session. The edema probably contributed to the positive results after three months, togheter with the new collagen and elastic fibers organization. The greater edema after the 2940nm session indicates that dermal remodeling takes longer than with 1540nm. It is possible that this histological superiority relates to a more prolonged effect, but a cohort longer than three months is needed to confirm that supposition.


[Preinvasive lesions in gynaecology - ovary].
In comparison to malignant tumors of vulva, vagina, cervix and uterine corpus, clear morphologic and molecular genetic features of precursor lesions of ovarian carcinoma have not been defined yet. We can see an effort to describe preinvasive lesions to allow dia-gnostics and treatment prior to development of invasive ovarian cancer. This tendency is magnified by the fact that ovarian carcinomas have the highest mortality from all gynecological malignancies. Currently, reports confirming different morphology, pathogenesis and molecular alterations in heterogeneous group of ovarian carcinomas have been described. There is a tendency to divide epithelial malignant tumors into two groups. Low grade ovarian serous carcinoma, low grade endometrioid, clear cell, mucinous ovarian cancers and Brenner tumors of ovary are categorized as type I ovarian tumors. Highgrade serous carcinoma, undifferentiated carcinomas and malignant mixed mesodermal tumors of the ovary (MMMTs) belong to type II tumors. A potential precursor lesion of highgrade serous ovarian cancer has been defined - serous tubal intraepithelial carcinoma.


Insights into the evolution of vitamin B12 auxotrophy from sequenced algal genomes.
Vitamin B(12) (cobalamin) is a dietary requirement for humans because it is an essential cofactor for two enzymes, methylmalonyl-CoA mutase and methionine synthase (METH). Land plants and fungi neither synthesize or require cobalamin because they do not contain methylmalonyl-CoA mutase, and have an alternative B(12)-independent methionine synthase (METE). Within the algal kingdom, approximately half of all microalgal species need the vitamin as a growth supplement, but there is no phylogenetic relationship between these species, suggesting that the auxotrophy arose multiple times through evolution. We set out to determine the underlying cellular mechanisms for this observation by investigating elements of B(12) metabolism in the sequenced genomes of 15 different algal species, with representatives of the red, green, and brown algae, diatoms, and coccolithophores, including both macro- and microalgae, and from marine and freshwater environments. From this analysis, together with growth assays, we found a strong correlation between the absence of a functional METE gene and B(12) auxotrophy. The presence of a METE unitary pseudogene in the B(12)-dependent green algae Volvox carteri and Gonium pectorale, relatives of the B(12)-independent Chlamydomonas reinhardtii, suggest that B(12) dependence evolved recently in these lineages. In both C. reinhardtii and the diatom Phaeodactylum tricornutum, growth in the presence of cobalamin leads to repression of METE transcription, providing a mechanism for gene loss. Thus varying environmental conditions are likely to have been the reason for the multiple independent origins of B(12) auxotrophy in these organisms. Because the ultimate source of cobalamin is from prokaryotes, the selective loss of METE in different algal lineages will have had important physiological and ecological consequences for these organisms in terms of their dependence on bacteria.


Limited central side effects of a β-subunit subtype-selective GABAA receptor allosteric modulator.
GABAergic anxiolytics have well-documented centrally mediated side effects including sedation, potentiation of ethanol, tolerance, abuse liability and memory impairment. Most research directed towards identifying an anxioselective GABAergic therapeutic has been based upon the theory that these side effects could be mitigated by avoiding α1/5-subunit GABAA receptors while specifically targeting those with the α2/3-subunit. Unfortunately, there are prominent exceptions to this theory and it has yet to be translated into clinical success. We previously demonstrated that β2/3-subunit-selective GABAA receptor-positive allosteric modulators act as anxiolytics with reduced sedation and ethanol potentiation regardless of their activity at α1-subunit GABAA receptors. The prototypical β2/3-subunit-selective positive allosteric modulator, 2-261, is further characterized here for additional side effects commonly associated with central GABAA receptor activation. In mice, 10 times the anxiolytic dose (10 mg/kg) of 2-261 does not induce behavioral tolerance in the elevated plus maze following a 2 week subchronic treatment. In rats, an anxiolytic dose (10 mg/kg) of 2-261 is inactive in conditioned place preference, suggesting a reduced abuse liability. In rats, 10 times the anxiolytic dose (100 mg/kg) of 2-261 does not have a significant amnestic effect in the radial arm maze, suggesting a greater therapeutic index for memory impairment. These results suggest that β2/3-subunit subtype-selective GABAA receptor-positive allosteric modulators not only have reduced sedative liability, but also a reduction in other central side effects commonly associated with broader GABAA receptor activation. β2/3-subunit-selective compounds may represent a novel design template for anxiolytics with benzodiazepine-like efficacy and mitigated side effects.


The Arabidopsis GAI gene defines a signaling pathway that negatively regulates gibberellin responses.
The Arabidopsis gai mutant allele confers a reduction in gibberellin (GA) responsiveness. Here we report the molecular cloning of GAI and a closely related gene GRS. The predicted GAI (wild-type) and gai (mutant) proteins differ only by the deletion of a 17-amino-acid segment from within the amino-terminal region. GAI and GRS contain nuclear localization signals, a region of homology to a putative transcription factor, and motifs characteristic of transcriptional coactivators. Genetic analysis indicates that GAI is a repressor of GA responses, that GA can release this repression, and that gai is a mutant repressor that is relatively resistant to the effects of GA. Mutations at SPY and GAR2 suppress the gai phenotype, indicating the involvement of GAI, SPY, and GAR2 in a signaling pathway that regulates GA responses negatively. The existence of this pathway suggests that GA modulates plant growth through derepression rather than through simple stimulation.


Semaphorin 3F gene from human 3p21.3 suppresses tumor formation in nude mice.
Loss of heterozygosity on human chromosome 3p21.3 is a frequent occurrence in many tumor types. In a previous study, our laboratory demonstrated that an 80-kb P1 clone from chromosome 3 suppresses the tumorigenicity of the mouse fibrosarcoma cell line A9. Two cDNAs corresponding to genes encoded on this P1 clone, semaphorin 3F (SEMA3F) and N23, were tested for their effects on in vitro and in vivo growth characteristics after transfection into mouse A9 cells. Transfection of SEMA3F cDNA resulted in complete loss of tumorigenicity in nude mice, whereas transfection of N23 had no effect. Moreover, SEMA3F also functioned to block apoptosis of transfected A9 cells treated with Taxol or Adriamycin. The human ovarian adenocarcinoma cell line HEY showed a similar result as A9 cells, but the small cell lung cancer line GLC45 was unaffected by expression of SEMA3F.


Telemedicine experience of NYC Internal Medicine residents during COVID-19 pandemic.
The COVID-19 pandemic challenged the resilience of public health, including diagnostic testing, antiviral development and transmission prevention. In addition, it also affected the medical education of many residents and learners throughout the country. Historically, physicians undergoing their residency training were not involved in telemedicine. However, in response to the challenges faced due to COVID-19, the Accreditation Council for Graduate Medical Education (ACGME) released a provision in May 2020 to allow residents to participate in telemedicine. Lincoln Medical Center, located in the South Bronx of New York City, currently has 115 Internal Medicine residents, and telemedicine clinic visits have been conducted by residents since June 2020. An anonymous 25-question survey was sent to all Internal Medicine residents between August 8, 2020 to August 14, 2020. Of 115 residents, 95 (82.6% of the residents) replied to this questionnaire. Residents revealed feeling less confident in managing chronic diseases through telemedicine visits. The survey also shows that 83.1% of respondents prefer in-person visits during their training, 65.3% feel that the telemedicine experience will affect their future career choice, and 67.4% would prefer less than 50% of visits to be telemedicine in their future careers. The purpose of the new ACGME rules allowing telemedicine was to prevent the undertraining of residents and maintain health care for the patient during the COVID-19 pandemic. This affects residency training and the experiences of residents, which in turn can influence their future career plans.


Severe depression is associated with markedly reduced heart rate variability in patients with stable coronary heart disease.
The purpose of this study was to investigate the relationship between depression and heart rate variability in cardiac patients. Heart rate variability was measured during 24-hour ambulatory electrocardiographic (ECG) monitoring in 40 medically stable out-patients with documented coronary heart disease meeting current diagnostic criteria for major depression, and 32 nondepressed, but otherwise comparable, patients. Patients discontinued beta-blockers and antidepressant medications at the time of study. Depressed patients were classified as mildly (n = 21) or moderately-to-severely depressed (n = 19) on the basis of Beck Depression Inventory scores. There were no significant differences among the groups in age, gender, blood pressure, history of myocardial infarction, diabetes, or smoking. Heart rates were higher and nearly all indices of heart rate variability were significantly reduced in the moderately-to-severely versus the nondepressed group. Heart rates were also higher and mean values for heart rate variability lower in the mildly depressed group compared with the nondepressed group, but these differences did not attain statistical significance. The association of moderate to severe depression with reduced heart rate variability in patients with stable coronary heart disease may reflect altered cardiac autonomic modulation and may explain their increased risk for mortality.


Anesthetic Management of Adults With Epidermolysis Bullosa.
Epidermolysis bullosa (EB) is a group of rare, inherited diseases characterized by skin fragility and multiorgan system involvement that presents many anesthetic challenges. Although the literature regarding anesthetic management focuses primarily on the pediatric population, as life expectancy improves, adult patients with EB are more frequently undergoing anesthesia in nonpediatric hospital settings. Safe anesthetic management of adult patients with EB requires familiarity with the complex and heterogeneous nature of this disease, especially with regard to complications that may worsen during adulthood. General, neuraxial, and regional anesthetics have all been used safely in patients with EB. A thorough preoperative evaluation is essential. Preoperative testing should be guided by EB subtype, clinical manifestations, and extracutaneous complications. Advanced planning and multidisciplinary coordination are necessary with regard to timing and operative plan. Meticulous preparation of the operating room and education of all perioperative staff members is critical. Intraoperatively, utmost care must be taken to avoid all adhesives, shear forces, and friction to the skin and mucosa. Special precautions must be taken with patient positioning, and standard anesthesia monitors must be modified. Airway management is often difficult, and progressive airway deterioration can occur in adults with EB over time. A smooth induction, emergence, and postoperative course are necessary to minimize blister formation from excess patient movement. With careful planning, preparation, and precautions, adult patients with EB can safely undergo anesthesia.


[Thoracoscopic sympathectomy: a literature review].
Since its first description by Kux in 1954, the thoracic endoscopic (thoracoscopic) sympathectomy has rendered the open techniques obsolete in the treatment of the hyperhidrosis and other sympathetic-related diseases. AIM. The goal of this article is to present a critical review of the current indications, results and complications of the endoscopic thoracic sympathectomy. An extensive search and review of published papers on the thoracoscopic sympathectomy was undertaken. The thoracoscopic sympathectomy has evolved as a therapeutic choice in patients with focal hyperhidrosis, pain syndromes and peripheral vascular disorders, particularly. The results, recurrences and complications are similar to the previously established open procedures; nevertheless, the morbidity, the hospital stay and the time to return to activities of daily living are substantially reduced. The highest success and satisfaction rates (over 95%) were observed among patients treated for focal hyperhidrosis. The success and complication rates of thoracoscopic sympathectomy are comparable to those of open techniques, with an easier postoperative period and an earlier return to labor and daily living.


Pressure-diameter relations during early diastole in dogs. Incompatibility with the concept of passive left ventricular filling.
We studied left ventricular (LV) pressure-diameter relations in 13 open-chest mongrel dogs to explore whether ventricular filling is passive, active, or a combination of both. Left ventricular internal diameter along the minor axis and thickness of the LV free wall were measured with ultrasonic dimension gauges. Pressures in the LV, left atrium (LA), and aorta were measured with catheter-tip micromanometers. Pressure in the LV during the rapid filling phase of diastole decreased from 13 +/- 1 mm Hg to 3 +/- 0.4 mm Hg (mean +/- SE). During this period, LV internal diameter increased from 32.6 +/- 1.5 to 36.7 +/- 1.5 mm, and this represented 49% of the total change of LV diameter that occurred during diastole. The pressure-diameter relation that we observed during the rapid phase of filling suggests that active enlargement rather than passive distension of the left ventricle occurred. Reduction of pressure within the left ventricle during rapid filling, while the ventricular diameter increased, appears to be due to forces within the LV wall that act to restore the LV to its diastolic dimensions. This allows the LV to draw blood from the atrium by creating a pressure in the LV that is lower than in the LA. On the other hand, during the latter part of diastole, following atrial contraction, the pressure-diameter relation suggests that the left ventricle undergoes passive distention.


Exhaled Methane Is Associated with a Lower Heart Rate.
In humans, methane (CH4) is exclusively produced by the intestinal microbiota and has been implicated in several conditions including cardiovascular disease. After microbial production of CH4 in the gut, it steadily crosses into the systemic circulation and reaches the lungs where it can be detected in the exhaled breath, as a surrogate measure for intestinal CH4 production. Recent reports have shown an association between CH4 and vagal dysfunction as well as the inhibition of CH4 activity on ileal contractions with atropine, suggesting its action on the parasympathetic nervous system. Given these findings, we hypothesized that CH4 may be affecting resting heart rate (HR) based on the potential effect of CH4 on the vagus nerve. Given its possible role in the parasympathetic nervous system, we aimed to study the relationship between breath CH4 and resting HR in humans. Additionally, we performed a longitudinal study analyzing the change in HR and its association with breath CH4 over time. First, we reviewed 1,126 subjects and compared HR in subjects with detectable and undetectable breath CH4. Second, we performed a post hoc analysis of a randomized control trial to compare the change in HR for those who had an increase in breath CH4 versus those that had a decrease in breath CH4 over 14 weeks. Last, we assessed whether a larger decrease in CH4 is associated with a larger increase in HR over time. In the retrospective cohort, subjects with detectable CH4 had a lower HR compared to those with undetectable CH4 (73.0 ± 0.83 vs. 76.0 ± 0.44 beats/min, p = 0.01). In the post hoc analysis, a decrease in CH4 over time was associated with an increase in HR (median ∆ = 6.5 ± 8.32 beats/min, p = 0.0006). Last, we demonstrated a biological gradient whereby a larger drop in CH4 was associated with a greater increase in HR (R = -0.31, p = 0.03). Our findings suggest a potential role for the microbiome (and specifically CH4 from methanogens) to regulate HR. Considering these findings, mechanistic studies are warranted to further investigate this potential novel microbiome-neurocardiac axis.


Two-photon solvatochromism II: experimental and theoretical study of solvent effects on the two-photon absorption spectrum of Reichardt's dye.
In this study, we report on the influence of solvent on the two-photon absorption (2PA) spectra of Reichardt's dye (RD). The measurement of 2PA cross-sections is performed for three solvents (chloroform, dimethyl formamide, and dimethyl sulfoxide) using the Z-scan technique. The key finding of this study is the observation that the cross-section, corresponding to the 2PA of the intramolecular charge-transfer state, diminishes substantially upon increasing the solvent polarity. To unravel the solvent dependence of the 2PA cross-section, the electronic structure of RD is determined using a hybrid quantum mechanics/molecular mechanics (QM/MM) approach, in which polarization between the solute and solvent is taken into account by using a self-consistent scheme in the solvent polarization. The two-state approximation proves to be adequate for the studied system, and allowed the observed solvent-polarity-induced decrease of the 2PA cross-section to be related to the decrease of the transition moment and the increase in the excitation energy.


Cerebral blood flow effects of pain and acupuncture: a preliminary single-photon emission computed tomography imaging study.
The purpose of this study was to investigate the cerebral blood flow changes associated with the analgesic effect of acupuncture in patients with chronic pain. Seven patients presenting with a chronic pain syndrome and 5 healthy controls were included. All single-photon emission computed tomography (SPECT) scans were acquired with a uniform protocol. The patient group was injected with the radioisotope hexamethyl propyleneamine oxime (HMPAO) while experiencing their usual level of pain. A baseline scan was acquired approximately 20 minutes after administration of the HMPAO. The patient then underwent acupuncture therapy with needles placed in points specifically selected to relieve pain. When the pain improved, as determined by a 10-digit score for pain assessment, the patient was reinjected with HMPAO and imaged 20 minutes later for the acupuncture scan. The reference group also had a baseline and acupuncture scan, although the acupuncture itself was performed using a standardized set of needle points. The reference group participants were found to have significant increases in the thalamic and prefrontal cortex activity on the acupuncture scan compared to the baseline. The baseline scans of the pain patients showed significant asymmetric uptake in the thalami compared to controls. This asymmetry reversed or normalized after the acupuncture therapy. Significant correlations were observed between the change of activity in the prefrontal cortex and ipsilateral sensorimotor area. The results from these cases show that HMPAO-SPECT is capable of detecting changes in cerebral blood flow associated with pain and that acupuncture analgesia is associated with changes in the activity of the frontal lobes, brain stem, and thalami.


Inhibition of telomerase by 2'-O-(2-methoxyethyl) RNA oligomers: effect of length, phosphorothioate substitution and time inside cells.
2'-O-(2-methoxyethyl) (2'-MOE) RNA possesses favorable pharmocokinetic properties that make it a promising option for the design of oligonucleotide drugs. Telomerase is a ribonucleoprotein that is up-regulated in many types of cancer, but its potential as a target for chemotherapy awaits the development of potent and selective inhibitors. Here we report inhibition of human telomerase by 2'-MOE RNA oligomers that are complementary to the RNA template region. Fully complementary oligomers inhibited telomerase in a cell extract with IC(50) values of 5-10 nM at 37 degrees C. IC(50) values for mismatch-containing oligomers varied with length and phosphorothioate substitution. After introduction into DU 145 prostate cancer cells inhibition of telomerase activity persisted for up to 7 days, equivalent to six population doublings. Inside cells discrimination between complementary and mismatch-containing oligomers increased over time. Our results reveal two oligomers as especially promising candidates for initiation of in vivo preclinical trials and emphasize that conclusions regarding oligonucleotide efficacy and specificity in cell extracts do not necessarily offer accurate predictions of activity inside cells.


Atypical depression is more common than melancholic in fibromyalgia: an observational cohort study.
It has been postulated that atypical and melancholic depression subtypes exist in depressed fibromyalgia (FM) patients, yet no study has empirically tested this hypothesis. The purpose of this study is to determine whether major depressive disorder (MDD) with atypical features and MDD with melancholic features occurs in a FM sample and to describe their demographic, clinical and diagnostic characteristics. An observational cohort study using a descriptive cross-sectional design recruited a convenience sample of 76 outpatients with FM from an academic rheumatology clinic and a community mental health practice. Diagnoses of FM were confirmed using the 1990 ACR classification guidelines. Diagnoses of MDD and diagnostic subtypes were determined using the DSM-IV-TR criteria. Clinical characteristics were measured using the Fibromyalgia Impact Questionnaire, Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement and other standardized instruments. Odds ratios were computed on subtype-specific diagnostic criteria. Correlations assessed associations between subtype diagnoses and diagnostic criteria. Of the 76 subjects with FM, 11.8% (n = 9) were euthymic, 52.6% (n = 40) met diagnostic criteria for MDD with atypical features and 35.6% (n = 27) for MDD with melancholic features. Groups did not differ on demographic characteristics except for gender (p = 0.01). The non-depressed and atypical groups trended toward having a longer duration of FM symptoms (18.05 yrs. +/- 12.83; 20.36 yrs. +/- 15.07) compared to the melancholic group (14.11 yrs. +/- 8.82; p = 0.09). The two depressed groups experienced greater severity on all clinical features compared to the non-depressed group. The atypical group did not differ clinically from the melancholic group except the latter experienced greater depression severity (p = 0.001). The atypical group demonstrated the highest prevalence and correlations with atypical-specific diagnostic criteria: (e.g., weight gain/ increased appetite: OR = 3.5, p = 0.02), as did the melancholic group for melancholic-specific criteria: (e.g., anhedonia: OR = 20, p < 0.001). Depressed fibromyalgia patients commonly experience both atypical and melancholic depressive features; however, in this study, atypical depression was 1.5 times more common than melancholic depression. This finding may have significant research and clinical implications.


An Enhanced Classification Framework for Limited IoHT Time Series Data Using Ensemble Deep Learning and Image Encoding.
Recent studies have illuminated the potential of harnessing the power of Deep Learning (DL) and the Internet of Health Things (IoHT) to detect a variety of disorders, particularly among patients in the middle to later stages of the disease. The utilization of time series data has proven to be a valuable asset in this endeavour. However, the development of effective DL architectures for time series classification with limited data remains a critical gap in the field. Although some studies have explored this area, it is still an understudied and undervalued topic. Thus, there is a crucial need to address this gap and provide insights into designing effective architectures for time series classification with limited data, specifically in the context of healthcare-related time series data for rare diseases. The goal of this study is to investigate the possibility of making accurate predictions with a smaller time series dataset by using an Ensemble DL architecture. This framework is composed of a deep CNN model and transfer learning approaches like ResNet and MobileNet. The ensemble model proposed in this study was supplied with 3D images that were generated from time series data by using Recurrence Plot (RP), Gramian Angular Field (GAF), and Fuzzy Recurrence Plot (FRP) as the transformation techniques. The proposed method has shown promising classification accuracy, even when applied to a small dataset, and surpassed the performance of other state-of-the-art methods when tested on the ECG5000 dataset.Clinical relevance- The proposed deep learning architecture is capable of effectively handling limited clinical time series datasets, enabling the construction of robust models and accurate predictions.


Differential regulation of interleukin (IL)-12 p35 and p40 gene expression and interferon (IFN)-gamma-primed IL-12 production by IFN regulatory factor 1.
Interleukin (IL)-12 is a heterodimeric cytokine consisting of the p40 and p35 chains encoded on separate chromosomes. Coordinated expression of the two constituent genes is crucial for appropriate immune responses in timing, location, and magnitude. Interferon (IFN)-gamma priming of IL-12 production by macrophages represents an important physiological process in vivo for escalated cellular response to microbial infections. We provide evidence that IFN regulatory factor (IRF)-1-deficient macrophages have a selective impairment in mRNA synthesis of IL-12 p35 but not the p40 gene, and a strong deficiency in the production of IL-12 p70 but not p40. We demonstrate that the levels of IL-12 p35 protein stimulated by IFN-gamma and lipopolysaccharide (LPS) correspond to those of its mRNA, and that the nuclear factor kappaB signaling pathway is essential for the induction of IL-12 p35 transcription by LPS. IRF-1 plays a major role in the transcriptional activation of the IL-12 p35 gene, but not of the p40 gene, by physically interacting with an inverted IRF element within the IL-12 p35 promoter upon IFN-gamma activation. Moreover, IRF-1-mediated transcriptional activation of the p35 promoter requires the cooperation of two adjacent Sp1 elements. Thus, IRF-1 acts as a critical component of IFN-gamma signaling in the selective activation of IL-12 p35 transcription in synergy with LPS-mediated events.


Endoscopic Endonasal and Transcranial Surgery for Microsurgical Resection of Ventral Foramen Magnum Meningiomas: A Preliminary Experience.
Purely ventral foramen magnum meningiomas are challenging tumors to treat given their location, and proximity and relationship to vital neurovascular structures. To present endoscopic endonasal surgery (EES) as a complementary approach to the far-lateral suboccipital approach (FLA) for ventral midline tumors. From May 2008 to October 2013, 5 patients underwent EES and 5 FLA for primary ventral foramen magnum meningiomas. We retrospectively reviewed their records to evaluate outcomes. Nine of 10 patients presented with long-tract and lower cranial nerve deficits. All patients who presented with deficits preoperatively completely normalized after tumor resection regardless of approach. Gross total resection was achieved in 2 cases in the EES group and 4 cases in the FLA group (the rest were near total). Vascular encasement was a limitation to gross total resection with both approaches. Preoperative median Karnofsky Performance Scale score was 80 and improved to 100 in both groups. Following EES, 1 patient developed cerebrospinal fluid leak with resultant meningitis. Two patients developed hydrocephalus, one of which developed an epidural abscess following necrosis of the nasoseptal flap, requiring debridement. In the FLA group, 1 patient developed a pseudomeningocele associated with hydrocephalus. One patient developed an abdominal fat graft site hematoma. Both approaches provide excellent results for resection of ventral foramen magnum meningiomas, with reconstruction and hydrocephalus as the main sources of complication. In our practice, EES is a preferred technique in ventral, purely midline tumors with limited inferior extension and reduced lower cranial nerve manipulation, whereas FLA is preferred in tumors with lateral and caudal extension below the tip of the dens.


Dosimetric characteristics of a linear array of gamma or beta-emitting seeds in intravascular irradiation: Monte Carlo studies for the AAPM TG-43/60 formalism.
In principle, the AAPM TG-43/60 formalism for intravascular brachytherapy (IVBT) dosimetry of catheter-based sources is fully valid with a single seed of cylindrical symmetry and in the region comparable to or larger than the mean-free path of emitting radiation. However, for the geometry of a linear array of seeds within the few millimeter range of interest in IVBT, the suitability of the AAPM TG-43/60 formalism has not been fully addressed yet. We have meticulously investigated the dosimetric characteristics of catheter-based gamma (192Ir) and beta (90Sr/Y) sources using Monte Carlo methods before applying the AAPM TG-43/60 formalism. The dosimetric perturbation due to radiation interactions with neighboring seeds is at most 2% over the entire region of interest for the 192Ir source, while it increases to about 5% for the 90Sr/Y source. As the transaxial distance (y) increases beyond 3 mm, the sum of the dose contributions from neighboring seeds exceeds the dose contribution from the center seed for both sources. However, it continues to increase with the increasing y for 192Ir but is saturated beyond y = 5 mm for 9Sr/Y. Even within a few millimeters from the seeds, the dose from the low-energy betas of 192Ir is still less than 1% of the total dose. The radial dose and anisotropy functions are reformulated in reduced cylindrical coordinate with the reference point at y = 2 mm. The dose rate constant of 192Ir and the dose rate of 90Sr/Y at the reference point showed a fairly good agreement (within +/- 2%) with earlier studies and the NIST-traceable value, respectively. We conclude that the dosimetric perturbation caused by close proximity of neighboring seeds is nearly negligible so that the AAPM TG-43/60 formalism can be applied to a linear array of seeds.