Diabetes care among Somali immigrants and refugees.
The risk for development of diabetes and associated complications among immigrants increases in the years after arrival to the United States. Somali immigrants and refugees represent the largest subset of African immigrants to the United States, yet little is known about the quality of their diabetes care. Therefore, adherence with diabetes quality indicators (Hemoglobin A1C <7%, LDL cholesterol <100 mg/dl, blood pressure <130/80 mm Hg) were compared between Somali and non-Somali patients with diabetes at a large academic primary care practice in the United States in 2008. Demographic and health-seeking behavior variables were assessed for association with adherence among the Somali population. A total of 5,843 non-Somali and 81 Somali patients with diabetes were identified. Somali patients with diabetes were less likely to meet the criteria for optimal glycemic control than non-Somali patients (40.6% vs. 53.9%; P=0.02). There was a similar, though statistically non-significant, trend towards lower rates of lipid control among Somali patients. There was no difference in achievement of optimal blood pressure between the two groups. There was a strong association between number of primary care visits during the study interval and achievement of all three diabetes care quality goals. This study demonstrates disparities in achievement of diabetes management quality goals among Somali patients compared with non-Somali patients, highlighting the need for additional system and practice changes to target this particularly vulnerable population.


Intimate partner problems and suicide: are we missing the violence?
Suicide consistently ranks in the top ten causes of death nationally. The purpose of this study was to develop a novel coding scheme to determine what percentage of suicide cases from 2005-2015 in Kentucky involved violence when intimate partner problems were identified. Currently, researchers using the national dataset, containing these data, only have the option to identify intimate partner problems unless each case is reviewed individually. Data from the Kentucky Violent Death Reporting System from 2005-2015 were used to create a subset of cases where intimate partner problems were identified and qualitative and quantitative analysis of the death scene investigation incident narratives was conducted to identify cases where intimate partner violence also contributed to the suicide. Intimate partner problems were identified in 1,327 (26%) of all suicide cases where circumstances were known and intimate partner violence in 575 (43%) cases identified as having intimate partner problems. There was an argument or fight in 30% of cases where intimate partner problems were identified and most were immediately followed by the suicide. We did find supporting evidence of our hypothesis that there is a great deal of underlying and outright violence in intimate relationships, which is exacerbating the risk of suicide. This detailed coding schema guided abstractors to better identify intimate partner violence in suicides, which could be easily replicated.


Developmental delay in the Amazon: The social determinants and prevalence among rural communities in Peru.
The consequences of poor child development are becoming increasingly recognized. Programs are being put in place around the world to improve child development by providing healthy and stimulating environments for children. However, these programs often have limited reach and little is known about the prevalence of developmental delay in under-developed communities. The current study set-out to better understand the prevalence of developmental delay in rural communities in the Amazon region of Peru. Also, it explores social determinants that are associated with any delay. Cross-sectional study by evaluating developmental delay in children under 4 years utilizing Ages and Stages Questionnaire (ASQ-3). Additionally, conducting a social determinants questionnaire answered by caretakers to identify social drivers for developmental delay. The data was analyzed with multi-variant analysis to measure association. The prevalence of developmental delay in the Amazonian communities was 26.7% (19.3% in communication, 11.4% in gross motor skills, 8% in both) (N = 596). The multivariate logistic regression analysis revealed significant associations between developmental delay and; level of education (OR 0.64, p = 0.009), age of mother during child's birth (OR 0.96, p = 0.002), visits by community health agents (OR 0.73, p = 0.013), and river as primary water source (OR 2.39, p = 0.001). The social determinants questionnaire revealed that 39% of the mothers had their first child before the age of 17, nearly half stopped going to school before the age of 12 (52%), 29% gave birth at home, 13% breast fed for less than 7 months, and 50% of the children had diarrhea in the last month. There is still a great need to improve the conditions for child development in the Amazon region of Peru. One-fourth of the children suffer from developmental delay, which will likely impede their potentials for life unless something is done. The impact of education, age of mother at birth of the child, community health agents, and access to clean drinking water were important findings. Improvements can be made in these areas to create a large, cost-effective impact on the well-being of the communities.


Psychiatric comorbidity in pathological gambling: a critical review.
To critically review the current literature on pathological gambling as regards the significant psychiatric comorbidities associated with it. The authors synthesized information found via electronic searches (MEDLINE) and bibliographic-directed searches in over 60 publications. Pathological gamblers frequently have comorbid substance use disorders. In addition, a subset appear to have comorbid antisocial personality disorder, but they represent a minority when compared with those people who have acquired their antisocial traits as a consequence of their gambling behaviour. A comorbidity with the mood disorders is probable, but methodological concerns and inconsistencies with the data prevent further delineation of this. Emerging research for other disorders possibly associated with pathological gambling is also reviewed. Pathological gambling is associated with significant psychiatric comorbidity. Recommendations for future research are described.


Assessment of pathogenic bacteria using periodic actuation.
A new analytical platform for the assessment of pathogenic bacteria is presented. It is based on a robust technology which is able to amplify the signal to noise ratio providing fast and sensitive detection of target pathogenic bacteria. The system uses a custom made AC electrical impedance analyser to measure, using a lab on a chip platform, the oscillations of magnetically labelled analytes when applying a periodic magnetic field. The concentration of pathogenic Escherichia coli O157:H7 chosen as bacterial model was determined based on the amplitude of the electrical impedance oscillations at a selected AC frequency. The analytical platform provides a limit of detection of 10(2) cells ml(-1), has a fast analysis time, and is amenable for the detection of other target cells. The system has simple design suitable for portability and automated operation.


Feasibility of Multilevel Pregnancy Tests for Telemedicine Abortion Service Follow-Up: A Pilot Study.
Telemedicine clients wishing to confirm a successful medication abortion outside of a clinic setting are commonly instructed to use high-sensitivity urine pregnancy tests, which can take up to four weeks to yield accurate results. Multilevel urine pregnancy tests (MLPTs), which provide accurate results in one week, are a promising alternative, but their use has not been evaluated within telemedicine services. From November 2017 to May 2018, 165 eligible and consenting pregnant people who contacted safe2choose-an organization providing telemedicine abortion services internationally-for medication abortion were enrolled in a pilot study and mailed a package containing medication abortion drugs, two MLPTs and instructions. Data on 118 participants who completed a web-based evaluation survey two weeks after the package was sent were analyzed to examine participant experiences and satisfaction with the service. Responding participants were from 11 countries, including Mexico, the Philippines and Singapore. Ninety-three percent used both MLPTs, and 91% of those who used both tests used them at the correct time intervals. Among the 95% of participants whose MLPT results indicated that their pregnancy hormone levels decreased from before to after medication abortion, 86% correctly interpreted the results to mean that they were no longer pregnant. Satisfaction was high, with all indicating that the supplied information was helpful; more than nine out of 10 noted that they would want to use the MLPTs again. Incorporating MLPTs into telemedicine abortion services is feasible and associated with high client satisfaction. Enabling people to manage their own abortion follow-up care could greatly improve their overall abortion experience.


Thyroid cancer patients' involvement in adjuvant radioactive iodine treatment decision-making and decision regret: an exploratory study.
We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment. We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment. We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540). Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not.


Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly.
G-protein signaling depends on the ability of the individual subunits of the G-protein heterotrimer to assemble into a functional complex. Formation of the G-protein βγ (Gβγ) dimer is particularly challenging because it is an obligate dimer in which the individual subunits are unstable on their own. Recent studies have revealed an intricate chaperone system that brings Gβ and Gγ together. This system includes cytosolic chaperonin containing TCP-1 (CCT; also called TRiC) and its cochaperone phosducin-like protein 1 (PhLP1). Two key intermediates in the Gβγ assembly process, the Gβ-CCT and the PhLP1-Gβ-CCT complexes, were isolated and analyzed by a hybrid structural approach using cryo-electron microscopy, chemical cross-linking coupled with mass spectrometry, and unnatural amino acid cross-linking. The structures show that Gβ interacts with CCT in a near-native state through interactions of the Gγ-binding region of Gβ with the CCTγ subunit. PhLP1 binding stabilizes the Gβ fold, disrupting interactions with CCT and releasing a PhLP1-Gβ dimer for assembly with Gγ. This view provides unique insight into the interplay between CCT and a cochaperone to orchestrate the folding of a protein substrate.


Aluminium and the human breast.
The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified.


Case Report: Branch Retinal Vein Occlusion Post-mRNA SARS-CoV-2 (COVID-19) Vaccination.
Systemic thromboembolic complications are well documented to be associated with coronavirus disease 2019 (COVID-19); however, there have been a growing number of reports regarding ocular complications stemming from COVID-19 vaccinations. This case illustrates a clear temporal and possible causal relationship of COVID-19 vaccination with an ocular microvascular disorder, namely, retinal vein occlusion. This study aimed to report a case of inferotemporal branch retinal vein occlusion after messenger RNA Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A middle-aged woman developed right eye central scotoma 2 days after COVID-19 vaccination. She had transient hypertension during the first 2 days post-vaccination. A decrease in visual acuity (6/18) was documented. Initial retinal findings included flame-shaped hemorrhages and cotton-wool spots along inferotemporal branch retinal vessels. Optical coherence tomography revealed right eye cystoid macular edema. Laboratory investigation revealed mildly raised erythrocyte sedimentation rate and C-reactive protein. Other systemic examinations were unremarkable. She was treated for right eye inferotemporal branch retinal vein occlusion with cystoid macular edema and was given intravitreal anti-vascular endothelial growth factor monthly in three doses. Her visual acuity improved to 6/6 with resolved cystoid macular edema. This case illustrates a clear temporal and possible causal relationship between COVID-19 vaccination and retinal vein occlusion. Post-vaccination transient hypertension or the immunological and inflammatory response to the vaccine may have contributed to the venous occlusive event in this case. Eye care providers should remain aware of this possibility. The effectiveness of intravitreal anti-vascular endothelial growth factor for the treatment of macular edema secondary to branch retinal vein occlusion was demonstrated in this patient.


Near-infrared imaging of in vivo performance of orally administered solid forms to rats: Feasibility study with indocyanine green.
This study demonstrates the applicability of near-infrared (NIR) imaging to evaluating in vivo oral formulation performance. As a NIR probe and model drug, indocyanine green (ICG) and acetaminophen (ACE) were selected, respectively. The fluorescence intensity of ICG greatly increased upon dissolution, with the dissolved ICG passing through the gastrointestinal tract over time. Both compounds (0.05 mg of ICG and 0.5 mg of ACE) were encapsulated in gelatin and hydroxypropyl methylcellulose (HPMC) capsules in the solid form. In vitro, the HPMC capsules showed a disintegration lag time, a feature that was not observed for the gelatin capsules. After oral administration of each capsule to rats, blood samples were collected, followed by fluorescent imaging of the abdominal region. At 0.25 h after HPMC capsule administration, the fluorescence area and intensity were significantly small and relatively weak compared to that of the gelatin capsule. These tendencies resulted from the difference in capsule disintegration times, leading to a change in gastric emptying, which corresponded well with the initial time profile of the plasma concentration of ACE. These results indicate that possibility of NIR imaging with ICG to evaluate in vivo performance of orally administered formulations.


Energy doubling of 42 GeV electrons in a metre-scale plasma wakefield accelerator.
The energy frontier of particle physics is several trillion electron volts, but colliders capable of reaching this regime (such as the Large Hadron Collider and the International Linear Collider) are costly and time-consuming to build; it is therefore important to explore new methods of accelerating particles to high energies. Plasma-based accelerators are particularly attractive because they are capable of producing accelerating fields that are orders of magnitude larger than those used in conventional colliders. In these accelerators, a drive beam (either laser or particle) produces a plasma wave (wakefield) that accelerates charged particles. The ultimate utility of plasma accelerators will depend on sustaining ultrahigh accelerating fields over a substantial length to achieve a significant energy gain. Here we show that an energy gain of more than 42 GeV is achieved in a plasma wakefield accelerator of 85 cm length, driven by a 42 GeV electron beam at the Stanford Linear Accelerator Center (SLAC). The results are in excellent agreement with the predictions of three-dimensional particle-in-cell simulations. Most of the beam electrons lose energy to the plasma wave, but some electrons in the back of the same beam pulse are accelerated with a field of approximately 52 GV m(-1). This effectively doubles their energy, producing the energy gain of the 3-km-long SLAC accelerator in less than a metre for a small fraction of the electrons in the injected bunch. This is an important step towards demonstrating the viability of plasma accelerators for high-energy physics applications.


Photochemical Reactions of Glyoxal during Particulate Ammonium Nitrate Photolysis: Brown Carbon Formation, Enhanced Glyoxal Decay, and Organic Phase Formation.
Glyoxal is an important precursor of aqueous secondary organic aerosol (aqSOA). Its photooxidation to form organic acids and oligomers and reactions with reduced nitrogen compounds to form brown carbon (BrC) have been extensively investigated separately, although these two types of reactions can occur simultaneously during the daytime. Here, we examine the reactions of glyoxal during photooxidation and BrC formation in premixed NH4NO3 + Glyoxal droplets. We find that nitrate photolysis and photosensitization can enhance the decay rates of glyoxal by a factor of ∼5 and ∼6 compared to those under dark, respectively. A significantly enhanced glyoxal decay rate by a factor of ∼12 was observed in the presence of both nitrate photolysis and photosensitization. Furthermore, a new organic phase was formed in irradiated NH4NO3 + Glyoxal droplets, which had no noticeable degradation under prolonged photooxidation. It was attributed to the imidazole oxidation mediated by nitrate photolysis and/or photosensitization. The persistent organic phase suggests the potential to contribute to SOA formation in ambient fine particles. This study highlights that glyoxal photooxidation mediated by nitrate photolysis and photosensitization can significantly enhance the atmospheric sink of glyoxal, which may partially narrow the gap between model predictions and field measurements of ambient glyoxal concentrations.


Mediators of the relation between maternal depressive symptoms and child internalizing and disruptive behavior disorders.
Drawing on a normative sample of 224 youth and their biological mothers, this study tested 4 family variables as potential mediators of the relationship between maternal depressive symptoms in early childhood and child psychological outcomes in preadolescence. The mediators examined included mother-child communication, the quality of the mother-child relationship, maternal social support, and stressful life events in the family. The most parsimonious structural equation model suggested that having a more problematic mother-child relationship mediated disruptive behavior-disordered outcomes for youths, whereas less maternal social support mediated the development of internalizing disorders. Gender and race were tested as moderators, but significant model differences did not emerge between boys and girls or between African American and Caucasian youths.


[Role of the gas composition of intraocular fluid in the regulation of intraocular circulation].
The recovery velocity of the acido-alkaline state of the intraocular fluid depended upon the ocular hemodynamics in the rabbit intraocular chamber. Oppressive action of hyperoxia and substitute hypocapnia on intraocular blood circulation was revealed. The RQ reduction described in some eye diseases and after intraocular operations can be connected with changes in gaseous composition of the intraocular fluid.


Long-term endurance training induced changes in glucocorticoid receptors concentrations in rat and in man.
The responsiveness of target cells to glucocorticoids is directly related to the number and the functional state of intracellular glucocorticoid receptors (GR), which mediated the role of glucocorticoids. Although the effects of acute training on GR have been well characterized, less is known about the effects of chronic training on GR. The purpose of the present study was to describe the effects of long-term endurance training on GR. Male Sprague-Dawley rats were divided into 2 groups at random, 7 as controls and exercisers (swimming 40-50 min/day for 80 days), respectively. All rats were sacrificed 24 hours after their last training session for measurements of the GR in liver and brain cytosol and thymus cells by radioligand binding assay with 3H-dexamethasone. This study was also carried out on 8 trained adult, 8 aged as well as 6 retired athletes, whose GR in peripheral leukocytes were analyzed. GR in hepatic cytosol and intact thymus cells of rats were significantly lower in exercise group than those in the controls. But the apparent dissociation constant (kd) was not changed. The GR in brain cytosol of rats indicated no significant reduction after training. The GR in peripheral leukocytes of the adult and aged athletes were also significantly lower than that in the controls. However, there was no significant difference between the GR in the retired athletes and that in the controls. This study demonstrated that long-term endurance training could lead to a decrease in GR and that the changes in GR were reversible during training. The possible mechanisms and the physiological significance of these changes need to be determined.


Extrinsic tau-coupling and the regulation of interceptive reaching under varying task constraints.
We investigated a general theory accounting for the guidance of ongoing movements in an interceptive reaching task. The aim was to assess the premise of tau-coupling that the coupling constant k, the ratio of taus (τs) of motion gaps between hand and object, reflects the kinematics of the on-going movement. The spatial and temporal constraints of the interceptive action were manipulated in three task conditions. While the time dependent counterpart of k, K(t) exhibited task effects, k itself could not distinguish between task manipulations. K(t) showed large variability during the initial acceleration phase, small variability during the rest of the movement, and task dependent changes during the final deceleration phase of interception. The findings highlight the importance of clarifying what constitutes as t-coupling.


Effects of exposure to sexually explicit material on sexually violent behavior among first-year university men in Vietnam.
Adolescence and emerging adulthood represent a period of heightened vulnerability to sexual violence (SV). While some research suggests that exposure to sexually explicit material (SEM) among adolescents and college students is associated with sexually violent behavior, our understanding of this relationship is limited. This study aimed to assess the relationship between prior exposure to several types of SEM and sexually violent behavior in a sample of first-year university men in Vietnam. A cohort of 739 first-year male university students completed three survey waves over 14 months, providing information on contact and non-contact sexually violent behavior, exposure to SEM, and other theorized confounders of the SEM-SV relationship. Controlling for these covariates, we estimated the average treatment effect of SEM on contact and non-contact SV using the propensity score method. We also conducted a dose-response analysis for the effect of violent SEM on SV based on frequency-of-exposure classes derived from latent class analysis. The majority of the sample reported exposure to SEM in the prior six months, with 41% of the sample reporting exposure to violent SEM. In propensity-adjusted models, exposure to violent SEM, but not other types, had a small but significant positive effect on contact and non-contact SV. These effects increased for frequent viewers of violent SEM. Models of contact SV showed endogeneity, warranting caution. Exposure to violent SEM is prevalent among university men in Vietnam and may be contributing to sexually violent behavior. Incorporating media literacy into SV prevention programs to mitigate these potential effects may be warranted.


Gabapentin significantly decreases posthemorrhoidectomy pain: a prospective study.
Surgery for hemorrhoidectomy remains a painful procedure despite advances in pain management. Gabapentin is widely used for control of acute and chronic pain. Our aim was to evaluate the effect of gabapentin on posthemorrhoidectomy pain and opioid use. A prospective, open-label study. Patients requiring hemorrhoid surgery were recruited to be in control (standard of care) or treatment group (standard of care plus daily gabapentin). Twenty-one treatment and 18 control patients were recruited. One patient from study group and two patients from control group were excluded due to failure to follow up. Pain levels for gabapentin group were significantly lower on postoperative days 1, 7, and 14 compared to the standard treatment group (3.68 vs. 6.82 p < 0.01, 2.68 vs. 5 p = 0.02 and 0.75 vs. 3.64 p < 0.001 respectively). There was a trend toward less opioids taken in gabapentin group for postoperative days 1, 7, and 14 (4.69 vs. 6.36; 2.13 vs. 2.73, and 0.125 vs. 0.9) but it did not reach statistical significance. The average hemorrhoidal grade and number of hemorrhoidal complexes removed was slightly higher in gabapentin group. Five control group patients experienced postoperative complications versus two gabapentin group patients. No gabapentin related complications were seen in the treatment group. The average cost of gabapentin course was $5.34 per patient. Daily use of gabapentin in perioperative period significantly decreased reported levels of postoperative pain. This effective, inexpensive addition improves pain after hemorrhoid surgery. Randomized placebo-controlled studies would better define the usefulness of this medication for posthemorrhoidectomy pain.


Feminizing Sertoli cell tumor associated with Peutz-Jeghers syndrome.
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by the association of mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps and with an increased risk of developing gonadal sex tumors besides other malignancies. We describe a 7 1/2 year-old boy with PJS and bilateral gynecomastia. He has had buccal pigmentation since 1.5 years and had been operated for rectal polyp excision at 3.5 years. On physical examination, his height was at the 90th percentile, and his height age and bone age were 9 and 10 1/2 years, respectively. Increased melanotic buccal pigmentation of the lips and bilateral gynecomastia were noticed. Both of the testes were firm, non-tender and smooth on the surface, and each measured 8 ml. Hormonal measurements were all in the prepubertal range. Testis ultrasonography showed bilateral hyperechogenic areas within the glands. When he was operated for invagination and an ileum segment full of polyps was resected, bilateral testicular biopsies were also performed. Histopathological evaluation of the testes revealed bilateral multicentric benign Sertoli cell tumors. The aromatase inhibitor testolactone was started to slow skeletal maturation. On the basis of this and previous reports, PJS associated with sex-cord tumors is increasingly recognized in males as well as in females.


Pregnant and postpartum admissions to the intensive care unit: a systematic review.
To determine the incidence and characteristics of pregnant and postpartum women requiring admission to an intensive care unit (ICU). Medline, PubMed, EMBASE and CINAHL databases (1990-2008) were systematically searched for reports of women admitted to the ICU either pregnant or up to 6 weeks postpartum. Two reviewers independently determined study eligibility and abstracted data. A total of 40 eligible studies reporting outcomes for 7,887 women were analysed. All studies were retrospective with the majority reporting data from a single centre. The incidence of ICU admission ranged from 0.7 to 13.5 per 1,000 deliveries. Pregnant or postpartum women accounted for 0.4-16.0% of ICU admissions in study centres. Hypertensive disorders of pregnancy were the most prevalent indication for ICU admission [median 0.9 cases per 1,000 deliveries (range 0.2-6.7)]. There was no difference in the profile of ICU admission in developing compared to developed countries, except for the significantly higher maternal mortality rate in developing countries (median 3.3 vs. 14.0%, p = 0.002). Studies reporting patient outcomes subsequent to ICU admission are lacking. ICU admission of pregnant and postpartum women occurs infrequently, with obstetric conditions responsible for the majority of ICU admissions. The ICU admission profile of women was similar in developed and developing countries; however, the maternal mortality rate remains higher for ICUs in developing countries, supporting the need for ongoing service delivery improvements. More studies are required to determine the impact of ICU admission for pregnant and postpartum women.


Development and properties of surfactant-free water-dispersible Cu2ZnSnS4 nanocrystals: a material for low-cost photovoltaics.
A simple, yet novel hydrothermal method has been developed to synthesize surfactant-free Cu2ZnSnS4 nanocrystal ink in water. The environmentally friendly, 2-4 nm ultrafine particles are stable in water for several weeks. Detailed X-ray diffraction (XRD) and high-resolution transmission electron microscopy revealed the formation of single-crystalline-kesterite-phase Cu2ZnSnS4. Elemental mapping by scanning electron microscopy/energy dispersive spectrometry corroborated the presence of all four elements in a stoichiometric ratio with minor sulfur deficiency. Finally, Raman spectroscopy ruled out the possible presence of impurities of ZnS, Cu2SnS3, SnS, SnS2, Cu(2-x)S, or Sn2S3, which often interfere with the XRD and optical spectra of Cu2ZnSnS4. X-ray photoelectron spectroscopic studies of the as-synthesized samples confirmed that the oxidation states of the four elements match those of the bulk sample. Optical absorption analyses of thin film and solution samples showed high absorption efficiency (>10(4) cm(-1)) across the visible and near-infrared spectral regions and a band gap E(g) of 1.75 eV for the as-synthesized sample. A non-ohmic asymmetric rectifying response was observed in the I-V measurement at room temperature. The nonlinearity was more pronounced for this p-type semiconductor when the resistance was measured against temperature in the range 180-400 K, which was detected in the hot-point probe measurement.


Nucleation mode formation in heavy-duty diesel exhaust with and without a particulate filter.
Particle size distribution measurement with direct tailpipe sampling is employed to study the effect of a continuously regenerating diesel particulate filter (CRDPF) on emissions of a heavy-duty diesel engine. The CRDPF consists of an oxidation catalyst and a filter. Tests are conducted using 2 and 40 ppm sulfur content fuels and two steady-state driving modes. The formation of nucleation mode with and without CRDPF is found to depend on different parameters. Without after-treatment, size distribution is observed to have a nucleation mode only at low load. Being independent of the fuel sulfur level (with these low sulfur level fuels), this nucleation mode is suggested to form mainly from hydrocarbons. With a CRDPF-equipped engine, nucleation mode, which was not observed without CRDPF, was found at high load mode only. This nucleation mode formation was found to correlate positively with fuel sulfur content. It is suggested that sulfuric acid is a main nucleating species in this situation, resulting from the effective conversion of SO2 to SO3 in the oxidation catalyst. Using a thermodenuder confirms that the nucleation mode particles are semivolatile in nature.


A systematic review of propensity score methods in the acute care surgery literature: avoiding the pitfalls and proposing a set of reporting guidelines.
Propensity score methods are techniques commonly employed in observational research to account for confounding when estimating the effects of treatments and exposures. These methods have been increasingly employed in the acute care surgery literature in an attempt to infer causality; however, the adequacy of reporting and the appropriateness of statistical analyses when using propensity score matching remain unclear. The goal of this systematic review is to assess the adequacy of reporting of propensity score methods, with an emphasis on propensity score matching (to assess balance and the use of appropriate statistical tests), in acute care surgery (ACS) studies and to provide suggestions for improvement for junior investigators. We searched three databases, and other relevant literature (from January 2005 to June 2015) to identify observational studies within the ACS literature using propensity score methods (PROSPERO No: CRD42016036432). Two reviewers extracted data and assessed the quality of the studies retrieved by reviewing the adequacy of both overall reporting and of the propensity score matching methods used. A total of 49/71 (69%) of studies adequately reported propensity score methods overall. Matching was the most common propensity score method used in 46/71 (65%) studies, with 36/46 (78%) studies reporting matching methods adequately. Only 19/46 (41%) of matching studies reported the balance of baseline characteristics between treated and untreated subjects while 6/46 (13%) used correct statistical methods to assess balance. There were 35/46 (76%) of matching studies that explicitly used statistical methods appropriate for the analysis of matched data when estimating the treatment effect and its statistical significance. We have proposed reporting guidelines for the use of propensity score methods in the acute care surgery literature. This is to help investigators improve the adequacy of reporting and statistical analyses when using observational data to estimate effects of treatments and exposures.


Retrospective study of human cystic echinococcosis in Italy based on the analysis of hospital discharge records between 2001 and 2012.
Cystic echinococcosis (CE) is an important zoonotic parasitic infection. The European Centre for Disease Control highlights that Italy lacks a surveillance system for CE. Due to the lack of official data, we analysed the Hospital Discharge Records (HDRs) drawn from the National Ministry of Health. The aim of this study was to analyse data from the HDRs with CE-related diagnoses in Italy from 2001 to 2012 to assess the current status and trend of disease epidemiology. A total of 16,550 HDRs related to the admission of 10,682 Italian patients were examined. The HDRs were analysed according to the patient's region and province code to evaluate the demographic and clinical characteristics of each case, together with the annual incidence rates of hospital cases (AIh) in administrative divisions in rural and urban areas. Lesions occurred frequently in the liver (83.6%) and lungs (8.4%). Patients ranged in age from 1 to 100 years (mean 59.8), and 57% were over 60 years old. The highest average AIh was registered in the Islands with 4.6/10(5) inhabitants (6.9/10(5) in Sardinia and 4.3/10(5) in Sicily), followed by the South with an average AIh of 1.9/10(5) inhabitants (5.4/10(5) inhabitants) and the Centre with an average AIh of 1.07/10(5) inhabitants (there was an AIh of 1.65/10(5) in Latium). The analysis for trend showed a statistically significant decrease in the AIh throughout the study period (e.g., in the Islands r(2)=0.98, p<0.001). An AIh over 2/10(5) inhabitants was observed in 31/110 provinces. Rural areas with comprehensive development problems had a relative risk of CE of 5.7 (95% CI, 5.3 to 6.9) compared to urban areas. The relative risk increased between areas where sheep breeding is widespread compared to those where it is less prevalent. This study shows a detailed picture of the geographic distribution and the epidemiological situation of CE in Italy, indicating that CE continues to be a significant public health problem in Italy. The retrospective study of HDRs is useful for the evaluation of the status of disease epidemiology; however, a surveillance system is needed to report confirmed cases of human CE.


A novel role for coenzyme A during hydride transfer in 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
In this study, we take advantage of the ability of HMG-CoA reductase (HMGR) from Pseudomonas mevalonii to remain active while in its crystallized form to study the changing interactions between the ligands and protein as the first reaction intermediate is created. HMG-CoA reductase catalyzes one of the few double oxidation-reduction reactions in intermediary metabolism that take place in a single active site. Our laboratory has undertaken an exploration of this reaction space using structures of HMG-CoA reductase complexed with various substrate, nucleotide, product, and inhibitor combinations. With a focus in this publication on the first hydride transfer, our structures follow this reduction reaction as the enzyme converts the HMG-CoA thioester from a flat sp(2)-like geometry to a pyramidal thiohemiacetal configuration consistent with a transition to an sp(3) orbital. This change in the geometry propagates through the coenzyme A (CoA) ligand whose first amide bond is rotated 180° where it anchors a web of hydrogen bonds that weave together the nucleotide, the reaction intermediate, the enzyme, and the catalytic residues. This creates a stable intermediate structure prepared for nucleotide exchange and the second reduction reaction within the HMG-CoA reductase active site. Identification of this reaction intermediate provides a template for the development of an inhibitor that would act as an antibiotic effective against the HMG-CoA reductase of methicillin-resistant Staphylococcus aureus.


Characteristics of binge drinkers in Europe.
Binge drinking has been shown to be associated with considerable social harm and disease burden. This review aims to give an overview from a European perspective of the socio-demographical, individual, and social factors that affect binge drinking and to identify effective interventions to reduce binge drinking. To this end, a computer-assisted search of relevant articles was conducted. Results showed that males tended to binge drinking more frequently than females. Binge drinking was most prevalent among adolescents and young adults, and prevalence levelled off later in life. Socio-economic conditions seemed to have an effect on binge drinking, independent of their effects on the volume of alcohol consumed. The early onset of binge drinking was associated with a history of drinking in the family, but pathways into adulthood are less clear. Binge drinking often co-occurred with other substance use. Motives for binge drinking included both social camaraderie and tension reduction. Which aspect prevails may vary according to the type of binge drinker, but to date has not been satisfactorily explained. Binge drinkers were not likely to know enough about or be aware of the potential risks of bingeing. Pressure from peers was one of the strongest influencing factors for binge drinking and seemed to outweigh parental influences, especially from late adolescence onwards. Binge drinking also varied according to both the predominant adult and adolescent drinking culture with more binge drinking in the northern and middle parts of Europe compared to the southern parts. Thus, a variety of socio-demographical, individual, and social characteristics associated with binge drinking have been identified. However, knowledge in this area is limited, as most research has been conducted among particular groups in specific situations, in particular North American college students. More research in Europe is urgently needed, as results from other cultural backgrounds are difficult to generalize.


Popular medical concepts in Jamaica and their impact on drug use.
Universally, popular medical concepts form the basis of lay understanding of health, disease and cure. In Jamaica these concepts first developed in association with traditional herbal medicine. Now they are applied to the most common forms of primary care: over-the-counter and prescribed drugs. Research findings suggest that where there is disagreement between popular and professional medical models, as is the case in Jamaica, the effect of popular concepts is to increase self-medication and reduce adherence to prescribed medical regimens. To ameliorate this situation and the attendant potential risks for drug consumers, methods for providing needed drug information and improving physician-patient communication are suggested. These suggestions apply not only to Jamaicans living in Jamaica and the United States, but also to members of any group whose ethnomedical concepts differ from the biomedical training of physicians.


Rodent Diagnostic Testing.
Clinical medicine is an important part of scientific medicine that is all too often neglected when treating rodents and small mammal pets. As with more traditional pets, a progressive diagnostic regimen should include a thorough history, clinical signs, physical examination, and laboratory findings.


Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency disorder affecting over 400 million individuals worldwide. G6PD protects red blood cells (RBC) from the harmful effects of oxidative substances. There are more than 400 G6PD mutations, of which 186 variants have shown to be linked to G6PD deficiency by decreasing the activity or stability of the enzyme. Different variants manifest different clinical phenotypes which complicate comprehending the mechanism of the disease. In order to carry out computational approaches to elucidate the structural changes of different G6PD variants that are common to the Asian population, a complete G6PD monomer-ligand complex was constructed using AutoDock 4.2, and the molecular dynamics simulation package GROMACS 4.6.7 was used to study the protein dynamics. The G410D and V291M variants were chosen to represent classes I and II respectively and were created by in silico site-directed mutagenesis. Results from the Root mean square deviation (RMSD), Root mean square fluctuation (RMSF) and Radius of gyration (Rg) analyses provided insights on the structure - function relationship for the variants. G410D indicated impaired dimerization and structural NADP binding while the impaired catalytic activity for V291M was indicated by a conformational change at its mutation site.


Why do families enrol in paediatric weight management? A parental perspective of reasons and facilitators.
Few children with obesity who are referred for weight management end up enroled in treatment. Factors enabling enrolment are poorly understood. Our purpose was to explore reasons for and facilitators of enrolment in paediatric weight management from the parental perspective. Semi-structured interviews were conducted with parents of 10- to 17-year-olds who were referred to one of four Canadian weight management clinics and enroled in treatment. Interviews were audio-recorded and transcribed verbatim. Manifest/inductive content analysis was used to analyse the data, which included the frequency with which parents referred to reasons for and facilitators of enrolment. In total, 65 parents were interviewed. Most had a child with a BMI ≥95th percentile (n = 59; 91%), were mothers (n = 55; 85%) and had completed some post-secondary education (n = 43; 66%). Reasons for enrolment were related to concerns about the child, recommended care and expected benefits. Most common reasons included weight concern, weight loss expectation, lifestyle improvement, health concern and need for external support. Facilitators concerned the referral initiator, treatment motivation and barrier control. Most common facilitators included the absence of major barriers, parental control over the decision to enrol, referring physicians stressing the need for specialized care and parents' ability to overcome enrolment challenges. Healthcare providers might optimize enrolment in paediatric weight management by being proactive in referring families, discussing the advantages of the recommended care to meet treatment expectations and providing support to overcome enrolment barriers.


Encapsulation and controlled release of retinol from silicone particles for topical delivery.
Retinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few microencapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI. We have developed a class of silicone particles that addresses these challenges for the encapsulation, protection and controlled release of retinol and other hydrophobic compounds. The particles are prepared by the sol-gel polymerization of silane monomers, which enables their rapid and facile synthesis at scale while maintaining a narrow size distribution (i.e., CV < 20%). We show that our particles can: (i) encapsulate retinol with high efficiency (>85%), (ii) protect retinol from degradation (yielding a half-life 9× greater than unencapsulated retinol) and (iii) slowly release retinol over several hours (at rates from 0.14 to 0.67 μg cm-2 s-1/2). To demonstrate that the controlled release of retinol from the particles can reduce irritation, we performed a double blind study on human subjects and found that formulations containing our particles were 12-23% less irritating than identical formulations containing Microsponge® particles (an industry standard by Amcol, Inc.). To show that the silicone particles can elicit a favorable biological response, similar to the Microsponge® particles, we applied both formulations to reconstructed human epidermal tissues and found an upregulation of keratin 19 (K19) and a downregulation of K10, indicating that the reduced irritation observed in the human study was not caused by reduced activity. We also found a decrease in the production of interleukin-1α (IL-1α) compared to formulations containing the Microsponge particles, suggesting lower irritation levels and supporting the findings from the human study. Finally, we show that the silicone particles can encapsulate other AIs, including betamethasone, N, N-diethyl-meta-toluamide (DEET), homosalate and ingenol mebutate, establishing these particles as a true platform technology.


Catalysts of worker-to-worker violence and incivility in hospitals.
To identify common catalysts of worker-to-worker violence and incivility in hospital settings. Worker-to-worker violence and incivility are prevalent forms of mistreatment in healthcare workplaces. These are forms of counterproductive work behaviour that can lead to negative outcomes for employees, patients and the organisation overall. Identifying the factors that lead to co-worker mistreatment is a critical first step in the development of interventions targeting these behaviours. Retrospective descriptive study. Qualitative content analysis was conducted on the total sample (n = 141) of employee incident reports of worker-to-worker violence and incivility that were documented in 2011 at a large American hospital system. More than 50% of the incidents involved nurses, and the majority of incidents did not involve physical violence. Two primary themes emerged from the analysis: Work Behaviour and Work Organisation. Incidents in the Work Behaviour category were often sparked by unprofessional behaviour, disagreement over responsibilities for work tasks or methods of patient care, and dissatisfaction with a co-worker's performance. Incidents in the Work Organisation category involved conflicts or aggression arising from failure to following protocol, patient assignments, limited resources and high workload. Incidents of worker-to-worker violence and incivility stemmed from dissatisfaction with employee behaviour or from organisational practices or work constraints. These incident descriptions reflect worker dissatisfaction and frustration, resulting from poor communication and collaboration between employees, all of which threaten work productivity. Violence and incivility between hospital employees can contribute to turnover of top performers, hinder effective teamwork and jeopardise the quality of patient care. Identification of common catalysts for worker-to-worker violence and incivility informs the development of mistreatment prevention programmes that can be used to educate hospital staff.


Second trimester short cervix is associated with decreased abundance of cervicovaginal lipid metabolites.
A short cervix is a risk factor for preterm birth. The molecular drivers of a short cervix remain elusive. Metabolites may function as mediators of pathologic processes. We sought to determine if a distinct cervicovaginal metabolomic profile is associated with a short cervix (<25 mm) to unveil the potential mechanisms by which premature cervical remodeling leads to a short cervix. This was a secondary analysis of a completed prospective pregnancy cohort. Cervicovaginal fluid was obtained between 20 and 24 weeks' gestation. The participants selected for metabolomic profiling were frequency-matched by birth outcome and cervicovaginal microbiota profile. This analysis included 222 participants with cervical length measured. A short cervix was defined as one having length <25 mm, as measured by transvaginal ultrasound. Unpaired t-tests were performed with a Bonferroni correction for multiple comparisons. There were 27 participants with a short cervix, and 195 with normal cervical length. Of the 637 metabolites detected, 26 differed between those with a short cervix and those with normal cervical lengths; 22 were decreased, of which 21 belonged to the lipid metabolism pathway (all P<.000079). Diethanolamine, erythritol, progesterone, and mannitol or sorbitol were increased in the cases of short cervix. Among participants with Lactobacillus-deficient microbiota, only diethanolamine and mannitol or sorbitol differed between short cervix (n=17) and normal cervical length (n=75), both increased. A short cervix is associated with decreased cervicovaginal lipid metabolites, particularly sphingolipids. This class of lipids stabilizes cell membranes and protects against environmental exposures. Increased diethanolamine-an immunostimulatory xenobiotic-is associated with a short cervix. These observations begin to identify the potential mechanisms by which modifiable environmental factors may invoke cell damage in the setting of biological vulnerability, thus promoting premature cervical remodeling in spontaneous preterm birth.


Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor.
Polyglutamine (polyQ) tracts are regions of low sequence complexity frequently found in transcription factors. Tract length often correlates with transcriptional activity and expansion beyond specific thresholds in certain human proteins is the cause of polyQ disorders. To study the structural basis of the association between tract length, transcriptional activity and disease, we addressed how the conformation of the polyQ tract of the androgen receptor, associated with spinobulbar muscular atrophy (SBMA), depends on its length. Here we report that this sequence folds into a helical structure stabilized by unconventional hydrogen bonds between glutamine side chains and main chain carbonyl groups, and that its helicity directly correlates with tract length. These unusual hydrogen bonds are bifurcate with the conventional hydrogen bonds stabilizing α-helices. Our findings suggest a plausible rationale for the association between polyQ tract length and androgen receptor transcriptional activity and have implications for establishing the mechanistic basis of SBMA.


Thermo-optic design for microwave and millimeter-wave electromagnetic power microsensors.
Rendina et al. recently proposed the original configuration of an electromagnetic power sensor for microwaves and millimeter waves that is based on an optically interrogated all-silicon chip [Electron. Lett. 35, 1748 (1999)]. Here we theoretically analyze and discuss in detail the performances of such a new class of nonperturbing and wideband probe in terms of sensitivity, resolution, intrinsic detectivity, linearity, and response time. Good agreement between theory and experiments is demonstrated. In particular, minimum resolutions of approximately 1 mW/cm2 are obtained at frequencies beyond 10 GHz. The dependence of response on the geometrical and electromagnetic parameters of the sensing element is analyzed, and on this basis the possibility of achieving optimized configurations is discussed.


Development and in-house validation of an LC-MS/MS method for the quantification of the mycotoxins deoxynivalenol, zearalenone, T-2 and HT-2 toxin, ochratoxin A and fumonisin B1 and B2 in vegetable animal feed.
Animal feed can be contaminated with various mycotoxins. To ensure animal health and safe food and feed production, the European Commission has recommended increased monitoring of the co-occurrence of deoxynivalenol, zearalenone, ochratoxin A, fumonisin B(1) and B(2), T-2 and HT-2 toxin in feed. Thus, there is a need for an analytical method that enables their simultaneous detection and quantification. This paper describes the development and in-house validation of such a method, in which the mycotoxins were extracted from spiked and naturally contaminated cereal-based compound feed, corn and wheat. The extracts were divided into two aliquots where one was diluted and then analysed directly and the other was cleaned by using MultiSep(®)226 and then diluted and analysed. Separation and detection was achieved with LC-ESI-MS/MS by using a triple quadrupole instrument in the SRM mode. The precision (in terms of intra-day repeatability and inter-day reproducibility), accuracy, linearity, apparent recovery and expanded measurement uncertainty in feed, corn and wheat were evaluated. The LODs ranged from 1.0 to 72 μg/kg, and the LOQs ranged from 2.5 to 115 μg/kg. The apparent recovery was higher than 86% for all the mycotoxins, and the precision was better than that defined by the Horwitz equation for all concentrations. Proficiency test materials were analysed to assess the accuracy of the method, and the results were satisfactory for all seven mycotoxins. The method will be used to monitor the occurrence of these mycotoxins in products intended for animal feeding in Sweden.


Anti-GRP78 autoantibodies induce endothelial cell activation and accelerate the development of atherosclerotic lesions.
The 78-kDa glucose-regulated protein (GRP78) is an ER molecular chaperone that aids in protein folding and secretion. However, pathological conditions that cause ER stress can promote the relocalization of GRP78 to the cell surface (csGRP78), where it acts as a signaling receptor to promote cancer progression. csGRP78 also possesses antigenic properties, leading to the production of anti-GRP78 autoantibodies, which contribute to tumor growth. In contrast, the presence and role of anti-GRP78 autoantibodies in atherosclerosis is unknown. Here, we show that atherosclerotic-prone ApoE-/- mice develop circulating anti-GRP78 autoantibodies that bind to csGRP78 on lesion-resident endothelial cells. Moreover, GRP78-immunized ApoE-/- mice exhibit a marked increase in circulating anti-GRP78 autoantibody titers that correlated with accelerated lesion growth. Mechanistically, engagement of anti-GRP78 autoantibodies with csGRP78 on human endothelial cells activated NF-κB, thereby inducing the expression of ICAM-1 and VCAM-1, a process blocked by NF-κB inhibitors. Disrupting the autoantibody/csGRP78 complex with enoxaparin, a low-molecular-weight heparin, reduced the expression of adhesion molecules and attenuated lesion growth. In conclusion, anti-GRP78 autoantibodies play a crucial role in atherosclerosis development, and disruption of the interaction between anti-GRP78 autoantibodies and csGRP78 represents a therapeutic strategy.


HIV and AIDS, stigma and AIDS support groups: perspectives from women living with HIV and AIDS in central Thailand.
In this paper, community attitudes toward women living with HIV and AIDS at the present time from the perspectives of women in Thailand are examined. We also look at strategies women use in order to deal with any stigma and discrimination that they may feel or experience in the community. The paper is based on our larger study of the experiences of women living with HIV and AIDS and their participation in clinical trials. In late 2007 and early 2008 we carried out a number of in-depth interviews with women living with HIV and AIDS in central Thailand. We find that women living with HIV and AIDS still deal with stigma and discrimination in their everyday life. However, from the women's narratives, we also find more positive attitudes from local communities. Some women deal with stigma and discrimination by joining and participating in HIV and AIDS support groups that have emerged in response to the AIDS epidemic in Thailand. We argue that women are not passive victims, but that they act in their own agencies to counteract any negativity they might encounter.


Links between life course trajectories of family dysfunction and anxiety during middle childhood.
Using data from three waves of a large Canadian data set, we examine the relationship between two middle childhood trajectory variables, family dysfunction and anxiety. We draw upon family systems theory and developmental psychopathology, while attempting to expand their boundaries by capitalizing on the strengths within both approaches. Our data treatment strategy, guided by the life course analytical framework, included separate multivariate logits to examine this relationship, with and without the extent to, which selected explanatory risk variables predicted belonging to the highest family dysfunction trajectory. We also explored possible interactions between anxiety and explanatory risk variables. Supporting our hypothesis, a prolonged duration of high doses of family dysfunction was associated with the most extreme developmental trajectories of anxious behavior during middle childhood for both boys and girls. This relationship prevailed above and beyond the influence of other correlates of family dysfunction such as marital transition, socioeconomic status, family size, and depressive symptoms experienced by the informant (mostly mothers).


Group B streptococcal meningitis associated with a CSF fistula.
An elderly man had group B streptococcal meningitis. The infection may have seeded the meninges through a rhinocerebral fistula. Despite the frequency of nasopharyngeal colonization with this organism, reports of adult meningitis secondary to group B Streptococcus are rare; to our knowledge, no previous cases specifically associated with rhinocerebral fistula have been described. Reasons for the discrepancy between the frequency of nasopharyngeal colonization and the rarity of meningitis are suggested.


Identifying Potential Gamification Elements for A New Chatbot for Families With Neurodevelopmental Disorders: User-Centered Design Approach.
Chatbots have been increasingly considered for applications in the health care field. However, it remains unclear how a chatbot can assist users with complex health needs, such as parents of children with neurodevelopmental disorders (NDDs) who need ongoing support. Often, this population must deal with complex and overwhelming health information, which can make parents less likely to use a software that may be very helpful. An approach to enhance user engagement is incorporating game elements in nongame contexts, known as gamification. Gamification needs to be tailored to users; however, there has been no previous assessment of gamification use in chatbots for NDDs. We sought to examine how gamification elements are perceived and whether their implementation in chatbots will be well received among parents of children with NDDs. We have discussed some elements in detail as the initial step of the project. We performed a narrative literature review of gamification elements, specifically those used in health and education. Among the elements identified in the literature, our health and social science experts in NDDs prioritized five elements for in-depth discussion: goal setting, customization, rewards, social networking, and unlockable content. We used a qualitative approach, which included focus groups and interviews with parents of children with NDDs (N=21), to assess the acceptability of the potential implementation of these elements in an NDD-focused chatbot. Parents were asked about their opinions on the 5 elements and to rate them. Video and audio recordings were transcribed and summarized for emerging themes, using deductive and inductive thematic approaches. From the responses obtained from 21 participants, we identified three main themes: parents of children with NDDs were familiar with and had positive experiences with gamification; a specific element (goal setting) was important to all parents, whereas others (customization, rewards, and unlockable content) received mixed opinions; and the social networking element received positive feedback, but concerns about information accuracy were raised. We showed for the first time that parents of children with NDDs support gamification use in a chatbot for NDDs. Our study illustrates the need for a user-centered design in the medical domain and provides a foundation for researchers interested in developing chatbots for populations that are medically vulnerable. Future studies exploring wide range of gamification elements with large number of potential users are needed to understand the impact of gamification elements in enhancing knowledge mobilization.


[The Pro347Leu mutation of the rhodopsin gene in a Spanish family with autosomal dominant pigmentary retinosis].
We present a Spanish family affected with autosomal dominant pigmentary retinosis in which we have identified the mutation responsible for the disease (Pro347Leu) within the rhodopsin (RHO) gene. Complete ophthalmological and electrophysiological studies were performed in 14 members of this family. The molecular study, performed by SSCP analysis of the 5 exon and the promotor region of the rhodopsin gene, direct sequentiation and restriction analysis with the enzyme Mspl, showed a C-->T change in the second base of 347 codon of RHO gene. This mutation predicts a change of proline by leucine at this position. Every patient with the mutation showed a phenotype of diffuse, early onset and severe pigmentary retinosis with a little intrafamiliar variation. The Pro347Leu mutation, that has been very frequently described among all the populations, has been identified as a cause of RP in an Spanish family.


[Nutrition in elderly patients with cardiovascular diseases].
Elderly population is rapidly increasing in Turkey as well as in the world. There are a number of factors that affect the nutritional status of elderly. Factors such as physiological changes that occur with aging, socioeconomic factors, dementia, depression, large number of chronic illnesses and excessive use of drugs, and low intake of food on the grounds of illness affect the feeding of elderly. Cardiovascular diseases such as hypertension, ischemic heart disease and heart failure are more common in elderly and nutrition in these diseases is important in terms of mortality and morbidity.


Ictal ECG changes in temporal lobe epilepsy.
Changes in cardiac rhythm may occur during epileptic seizures and this has been suggested as a possible mechanism for sudden unexpected death amongst patients with chronic epilepsy (SUDEP). We have studied ECG changes during 61 complex partial seizures of temporal lobe origin in 20 patients. Tachycardia was observed in 24/61 (39%) and bradycardia in 3/61 (5%). The mean and median tachycardia rate was 139 and 140 beats/min (range 120-180). The longest R-R interval observed was 9 seconds. No difference was found in regard to the lateralisation of seizures and cardiac arrhytmia. One of the patients with bradycardia was fitted with a demand cardiac pacemaker, which appeared to decrease the number of his falls. In conclusion, ictal cardiac changes which may be seen in temporal lobe epilepsy (TLE) are sinus tachycardia and occasionally sinus bradycardia. Patients presenting vague complains suggestive of either TLE or cardiac dysrhythmia, simultaneous monitoring with EEG/ECG is required, and if the episodes are frequent, video-EEG should be considered. Further studies on this subject are warranted as this may shed some light on possible mechanisms for SUDEP.


Does maternal health voucher scheme have association with distance inequality in maternal and newborn care utilization? Evidence from rural Bangladesh.
Bangladesh has made substantial progress in maternal health. However, persistent inequities in service use undermine the achievements at the national level. In 2007, the government introduced a Maternal Health Voucher Scheme (MHVS) to reduce barriers to service utilization. The current study explores the impact of MHVS on reducing distance inequality in utilization across the maternal and newborn continuum of care (MNCoC). A cross-sectional survey was conducted from October'2017 to April'2018 in four selected MHVS sub-districts of Chattogram and Sylhet Divisions of Bangladesh. 2,400 women with at-least one child aged below two years were randomly selected. Both bivariate and multivariate analyses were carried out to explore the absolute and relative influence of the voucher scheme and chi-square test was used for hypothesis testing. Nineteen percent of the women were MHVS beneficiaries and 23% of them lived within 5 km of the health facility. Among the beneficiaries no significant differences were observed in the utilization of at-least 4 antenatal visits, skilled-assistance at delivery, postnatal care, and MNCoC between those living closer to the health facility and those living far away. However, a higher facility delivery rate was observed among beneficiary women living closer. By contrast, for non-beneficiaries, a significant difference was found in service use between women living closer to health facilities compared to those living further away. The study found the use of MNCoC to be similar for all MHVS beneficiaries irrespective of their distance to health facilities whereas non-beneficiary women living further away had lower utilization rates. MHVS could have potentially reduced distance-related inequality for its beneficiaries. However, despite the provision of transport incentives under MHVS the reduction in inequality in facility delivery was limited. We propose a revision of the transportation incentive adjusting for distance, geographical remoteness, road condition, and transport cost to enhance the impact of MHVS.


Insulin secretion in metabolically obese, but normal weight, and in metabolically healthy but obese individuals.
Metabolically obese but normal-weight (MONW) individuals present metabolic disturbances typical of obese individuals. Additionally, metabolically healthy but obese (MHO) individuals have been identified who are relatively insulin sensitive and have a favorable cardiovascular risk profile. We compared insulin secretion patterns of MONW and MHO with those of two age-matched groups comprising nonobese individuals or obese insulin-resistant subjects, respectively. To this end, 110 nonobese subjects and 87 obese subjects were stratified into quartile based on their insulin-stimulated glucose disposal (M(FFM)). Insulin secretion was estimated by acute insulin response (AIR) during an intravenous glucose-tolerance test (IVGTT), and the disposition index was calculated as AIR x M(FFM). We found that, as defined, M(FFM) was lower in MONW, who exhibited higher triglycerides, free-fatty acid (FFA), and 2-h postchallenge glucose levels compared to normal nonobese group. Insulin secretion was higher in MONW than in normal nonobese subjects, but disposition index was lower in MONW. Disposition index did not differ between MONW and insulin-resistant obese. M(FFM) was higher in MHO who exhibited lower waist circumference, blood pressure (BP), triglycerides, FFA, insulin levels, and higher high-density lipoprotein (HDL) cholesterol compared to insulin-resistant obese. Insulin secretion did not differ between insulin-resistant obese and MHO, but disposition index was lower in the former group. In conclusion, MONW and insulin-resistant obese showed decreased compensatory insulin secretion compared to normal nonobese and MHO subjects, respectively. Because these subjects also exhibited a worse metabolic risk profile, these findings may account for their increased risk for type 2 diabetes.


Structure of a human multidrug transporter in an inward-facing conformation.
Multidrug resistance protein 1 (ABCC1) is a member of the 'C' class of ATP-binding cassette transporters, which can give rise to resistance to chemotherapy via drug export from cells. It also acts as a leukotriene C4 transporter, and hence has a role in adaptive immune response. Most C-class members have an additional NH(2)-terminal transmembrane domain versus other ATP-binding cassette transporters, but little is known about the structure and role of this domain. Using electron cryomicroscopy of 2D crystals, data at 1/6per A(-1) resolution was generated for the full-length ABCC1 protein in the absence of ATP. Analysis using homologous structures from bacteria and mammals allowed the core transmembrane domains to be localised in the map. These display an inward-facing conformation and there is a noteworthy separation of the cytoplasmic nucleotide-binding domains. Examination of non-core features in the map suggests that the additional NH(2)-terminal domain has extensive contacts on one side of both core domains, and mirrors their inward-facing configuration in the absence of nucleotide.


Fabrication of hollow metal oxide nanocrystals by etching cuprous oxide with metal(II) ions: approach to the essential driving force.
Hollow metal oxide nanocrystals were prepared by etching cuprous oxide with metal ions and were applied as photoelectrodes. As a hard template, polyvinylpyrrolidone stabilized cuprous oxide (PVP-Cu2O) and non-stabilized cuprous oxide (nPVP-Cu2O) were synthesized by a precipitation method. Hollow iron oxide and cobalt oxide nanocrystals with a truncated octahedral morphology were fabricated by an etching reaction with transition metal(II) ions (Fe(2+) or Co(2+)). In the etching reaction process, a cationic exchange reaction occurs between the divalent metal ion and Cu(+) due to the higher Lewis acidity. Facet selective etching of cuprous oxide has been observed during the ionic exchange reaction of Cu(+) and O(2-) ions in PVP-Cu2O complexes with transition metal(II) ions (Fe(2+) or Co(2+)) at the surface of a (110) facet. Amorphous states of hollow metal oxide products were annealed to form α-Fe2O3 (hematite) and Co3O4 and their crystal structure was examined with X-ray diffraction and HR-TEM. The optical absorption behavior of semiconductor nanocrystals was measured with UV-vis spectroscopy to define band gap energy. The hollow hematite structure has a 2.08 eV band gap and Co3O4 (Co(II,III) oxide) has a 1.80 eV indirect band gap. Using these hollow nanocrystals, a metal oxide monolayer film was fabricated with a secondary growth approach and was studied for its photocatalytic properties.


The E6 and E7 genes of human papilloma virus-type 16 protect primary astrocyte cultures from injury.
Many oncogenes are implicated in the regulation of apoptosis as well as in control of the cell cycle, and several have been shown to protect cells from injury. We tested whether the expression of human papillomavirus type 16 genes E6 and E7 could protect primary astrocytes from injury. Retroviral vectors were used to express E6, E7, or E6E7 in primary murine astrocyte cultures. Astrocytes expressing E6E7 suffered less than half the injury seen in controls after exposure to 400 microM H2O2. When we compared astrocytes expressing only E6 or E7, cells expressing E7 alone were protected to a greater extent and from more severe injury than those expressing E6. E6E7, E6 and E7 all provided protection from 30 h glucose deprivation, but again E7 provided the best protection, reducing injury to less than a third of that seen in controls. Expression of E7 alone decreases vulnerability to both hydrogen peroxide and glucose deprivation injury while E6 alone primarily decreases glucose deprivation injury. These results demonstrate that expression of human papillomavirus oncogenes can reduce the vulnerability of astrocytes to oxidative stress and nutrient deprivation.


Evaluation of 3D Additively Manufactured Canine Brain Models for Teaching Veterinary Neuroanatomy.
Physical specimens are essential to the teaching of veterinary anatomy. While fresh and fixed cadavers have long been the medium of choice, plastinated specimens have gained widespread acceptance as adjuncts to dissection materials. Even though the plastination process increases the durability of specimens, these are still derived from animal tissues and require periodic replacement if used by students on a regular basis. This study investigated the use of three-dimensional additively manufactured (3D AM) models (colloquially referred to as 3D-printed models) of the canine brain as a replacement for plastinated or formalin-fixed brains. The models investigated were built based on a micro-MRI of a single canine brain and have numerous practical advantages, such as durability, lower cost over time, and reduction of animal use. The effectiveness of the models was assessed by comparing performance among students who were instructed using either plastinated brains or 3D AM models. This study used propensity score matching to generate similar pairs of students. Pairings were based on gender and initial anatomy performance across two consecutive classes of first-year veterinary students. Students' performance on a practical neuroanatomy exam was compared, and no significant differences were found in scores based on the type of material (3D AM models or plastinated specimens) used for instruction. Students in both groups were equally able to identify neuroanatomical structures on cadaveric material, as well as respond to questions involving application of neuroanatomy knowledge. Therefore, we postulate that 3D AM canine brain models are an acceptable alternative to plastinated specimens in teaching veterinary neuroanatomy.


Human granulocyte-macrophage colony-stimulating factor (hGM-CSF): identification of a binding site for a neutralizing antibody.
One approach to the localization of functionally active regions of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) is to map the epitopes recognized by neutralizing anti-hGM-CSF monoclonal antibodies. We have defined the epitope recognized by one neutralizing antibody (LMM102) using proteolytic fragments obtained by enzymic digestion of bacterially synthesized hGM-CSF. RP-HPLC fractionation of a tryptic digest resulted in the identification of an immunoreactive "tryptic core" peptide containing 66 amino acids (52% of the protein). Further digestion of this "tryptic core" with S. aureus V8 protease produced a unique immunoreactive hGM-CSF product comprising two peptides, residues 86-93 and 112-127, linked by a disulfide bond between residues 88 and 121. The individual peptides, generated by reduction with dithiothreitol, were not recognized by the antibody. An analog of this peptide has been synthesized chemically and shown to have similar immunoreactivity to the epitope obtained by enzymic digestion. A series of modified peptides has also been synthesized to identify further the region required for antibody recognition.


Developing an Intranet-Based Lymphedema Dashboard for Breast Cancer Multidisciplinary Teams: Design Research Study.
A large quantity of data is collected during the delivery of cancer care. However, once collected, these data are difficult for health professionals to access to support clinical decision making and performance review. There is a need for innovative tools that make clinical data more accessible to support health professionals in these activities. One approach for providing health professionals with access to clinical data is to create the infrastructure and interface for a clinical dashboard to make data accessible in a timely and relevant manner. This study aimed to develop and evaluate 2 prototype dashboards for displaying data on the identification and management of lymphedema. The study used a co-design framework to develop 2 prototype dashboards for use by health professionals delivering breast cancer care. The key feature of these dashboards was an approach for visualizing lymphedema patient cohort and individual patient data. This project began with 2 focus group sessions conducted with members of a breast cancer multidisciplinary team (n=33) and a breast cancer consumer (n=1) to establish clinically relevant and appropriate data for presentation and the visualization requirements for a dashboard. A series of fortnightly meetings over 6 months with an Advisory Committee (n=10) occurred to inform and refine the development of a static mock-up dashboard. This mock-up was then presented to representatives of the multidisciplinary team (n=3) to get preliminary feedback about the design and use of such dashboards. Feedback from these presentations was reviewed and used to inform the development of the interactive prototypes. A structured evaluation was conducted on the prototypes, using Think Aloud Protocol and semistructured interviews with representatives of the multidisciplinary team (n=5). Lymphedema was selected as a clinically relevant area for the prototype dashboards. A qualitative evaluation is reported for 5 health professionals. These participants were selected from 3 specialties: surgery (n=1), radiation oncology (n=2), and occupational therapy (n=2). Participants were able to complete the majority of tasks on the dashboard. Semistructured interview themes were categorized into engagement or enthusiasm for the dashboard, user experience, and data quality and completeness. Findings from this study constitute the first report of a co-design process for creating a lymphedema dashboard for breast cancer health professionals. Health professionals are interested in the use of data visualization tools to make routinely collected clinical data more accessible. To be used effectively, dashboards need to be reliable and sourced from accurate and comprehensive data sets. While the co-design process used to develop the visualization tool proved effective for designing an individual patient dashboard, the complexity and accessibility of the data required for a cohort dashboard remained a challenge.


A point mutation in the nucleotide exchange factor eIF2B constitutively activates the integrated stress response by allosteric modulation.
In eukaryotic cells, stressors reprogram the cellular proteome by activating the integrated stress response (ISR). In its canonical form, stress-sensing kinases phosphorylate the eukaryotic translation initiation factor eIF2 (eIF2-P), which ultimately leads to reduced levels of ternary complex required for initiation of mRNA translation. Previously we showed that translational control is primarily exerted through a conformational switch in eIF2's nucleotide exchange factor, eIF2B, which shifts from its active A-State conformation to its inhibited I-State conformation upon eIF2-P binding, resulting in reduced nucleotide exchange on eIF2 (Schoof et al. 2021). Here, we show functionally and structurally how a single histidine to aspartate point mutation in eIF2B's β subunit (H160D) mimics the effects of eIF2-P binding by promoting an I-State like conformation, resulting in eIF2-P independent activation of the ISR. These findings corroborate our previously proposed A/I-State model of allosteric ISR regulation.


Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer.
The combination of fulvestrant with alpelisib, a PI3K inhibitor, improves progression-free survival in metastatic hormone receptor-positive, PIK3CA-mutant breast cancer. This study describes the incidence, risk factors, and treatment of alpelisib-associated hyperglycemia. Patients with metastatic breast cancer who received alpelisib from 2013 to 2021 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Alpelisib prescription dates and patient/tumor characteristics were abstracted from medical records. Risk factors associated with hyperglycemia and alpelisib dose reduction/discontinuation were evaluated using Pearson's χ2 tests. Among 247 patients, baseline median body mass index was 25.4 kg/m2 and median hemoglobin A1c (HbA1c) was 5.5%. A total of 152 patients (61.5%) developed any-grade hyperglycemia and 72 patients (29.2%) developed grade 3-4 hyperglycemia; median time to onset was 16 days. A total of 100 patients (40.5%) received alpelisib on a clinical trial; rates of hyperglycemia were significantly higher in patients treated as standard care versus on a clinical trial (any-grade hyperglycemia 80.3% vs. 34.0%, grade 3-4 hyperglycemia 40.2% vs. 13.0%, p < .001). Baseline HbA1c was significantly associated with development of hyperglycemia (p < .001) and alpelisib dose reduction/discontinuation (p = .015). Among those who developed hyperglycemia, 101 (40.9%) received treatment, most commonly with metformin. A total of 49 patients (19.8%) were referred to an endocrinologist, which was associated with SGLT2 inhibitor prescription (p = .007). Rates of hyperglycemia among patients treated with alpelisib as standard care were significantly higher than patients treated on clinical trials. Elevated baseline HbA1c is associated with alpelisib-induced hyperglycemia and requiring dose modification. Optimization of glycemic status before alpelisib initiation should become routine practice.


Effectiveness of an Educational Intervention in Reducing New International Postgraduates' Acculturative Stress in Malaysian Public Universities: Protocol for a Cluster Randomized Controlled Trial.
Universities around the world, including Malaysia, have attracted many international students from different countries. Research has reported that acculturative stress resulting from international students' attempts to adjust to the cultures of host countries is one of the most challenging issues that affects their lives in general and academic lives in particular. This study aims to examine the effectiveness of an educational intervention on acculturative stress among new postgraduate international students joining Malaysian public universities. A cluster randomized controlled trial design with Malaysian public universities as the unit of randomization will be used in this study. Public universities will be randomized in a 1:1 ratio to be either in the intervention (educational program) or control group (waiting list). Participants in the intervention group will receive 7 sessions in 9 hours delivered by an expert in psychology and the researcher. The control group will receive the intervention once the 3-month follow-up evaluation is completed. The data will be analyzed using the generalized estimation equation with a confidence interval value of 95%; significant differences between and within groups are determined as P<.05. The results of the study underlie the effectiveness of educational program in decreasing acculturative stress of new international students and enabling them to cope with a new environment. The results of this study will contribute to previous knowledge of acculturative stress, acculturation, and adjustment of international students. Furthermore, such results are expected to play a role in raising university policy makers' awareness of their postgraduate international students' acculturative stress issues and how they can help them avoid such stress and perform well in their academic life. We expect that the intervention group will score significantly lower than the wait-list group on the immediate and 3-month postintervention evaluation of acculturative stress and achieve a higher level of adjustment. Results will have implications for international students, policy makers at universities, the Malaysian Ministry of Higher Education, and future research. Clinical Trials Registry India CTRI/2018/01/011223; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1= 21978&EncHid=&userName=Muhamad%20Hanafiah%20Juni. PRR1-10.2196/12950.


[Endometriosis in delayed scarring of postpartum eutocic episiorrhaphy. Integral aspects and a case report].
Endometriosis remains a mystery because it has not yet been shown why these cells are viable in the abdominal cavity, although it has been thought that the immune system plays a role in implantation outside the intrauterine cavity by abasement in the regulatory capacity of natural killer cells, as well as peripheral and peritoneal immunologic cells. Among methods used to recognize this illness are laparoscopy, laparotomy, ultrasound, antibodies, and the histologic study. It has been observed that surgical scars can present cyclical inflammation and pain when affected with this pathology. We present the case of a patient with a second delivery who arrived at the Gynecology Service due to referring intense pain in the episiorrhaphy scar as well as superficial dyspareunia. One year after performance of the surgical procedure, pain did not allow the patient was unable to sit normally; in addition, during the last 3 months the area of the cicatrix augmented in volume during menstruation. Under peridural block and with surgical spindle excision, the abnormal tissue was dissected without complications; the surgery showed brittle tissue and with abundant new vascularity. The histologic diagnosis reported vulvar-tissue endometriosis. Was initiate complementary treatment was initiated with gestrinon once a week for 4 weeks, as well as danazol daily for 2 months to avoid possible persistence of endometrial tissue. The scar at present is minimal and is observed along the borders of the surgical union line, without an increase in size nor discomfort on digital pressure. We consider it necessary to assure cleaning of the episiotomy before initiating surgical suturing to diminish presence of endometriosis, despite the fact that incidence of this disturbance is low (0.03%). Advancement in knowledge of the physiopathology process will permit elimination of the remaining endometrial tissue with new therapeutic strategies, as well as clearing up the mechanism of ectopic implantation of endometrial cells.


Leukopenia, lymphopenia, and neutropenia in systemic lupus erythematosus: Prevalence and clinical impact--A systematic literature review.
To systematically review the available evidence to evaluate (1) the prevalence and degree of leukopenia, lymphopenia, and neutropenia in patients with systemic lupus erythematosus (SLE), (2) whether these conditions carry a major infection risk for patients, and (3) whether a treatment with colony stimulating factors (CSF) can be an effective and safe option in SLE patients with leukopenia. MedLine and Embase were searched by including MeSH terms, text words, and subheadings "systemic lupus erythematosus," "leukopenia" (first search), and "colony stimulating factor" (second search). Inclusion and exclusion criteria were a priori defined and two reviewers screened the retrieved articles for selection criteria; data from the included studies were recorded in ad hoc standard forms; the results were synthesized and transported to evidence tables. A total of 17 articles were included in the systematic literature review: nine articles were retrieved for the first research question and 11 for the second while no articles satisfied the inclusion criteria for the third research question. The prevalence of leukopenia is reported in 22-41.8% of cases and lymphopenia is reported cumulatively from 15% to 82% of the patients while neutropenia is described in 20-40% of the patients. There is no evidence of a significant association between overall reduction of white blood cells and infection occurrence while some studies found a strong association between low lymphocytes/neutrophils count and the risk of major infections. Only case reports and case series have been found to investigate the safety of CSF in SLE patients. The results of this systematic literature review are inconclusive for many aspects related to the original research questions and highlight the need for further studies. Indeed, the strength of the evidence is not sufficiently robust to draw specific recommendations on how to balance between the need to treat the patient with SLE with immunosuppressive drugs and the risk of severe infections.


Atypical squamous cells of undetermined significance in girls and women.
To estimate the outcome of adolescents with atypical squamous cells of undetermined significance (ASC-US) on cytology. A review of ASC-US cytology in girls and women aged 10-19 years between 1995 and 1999 was performed. The cytologic and histologic follow-up of each patient was evaluated. The outcome was recorded as the most significant (highest grade) subsequent cervical smear or biopsy. Overall, 535 of 7897 (6.8%) cervical cytologic specimens were reported as ASC-US. The study group consisted of 398 patients for whom pathologic follow-up was available. The mean duration of follow-up was 19 months. Follow-up consisted of repeat cytology in 251 (63%) patients and colposcopy with cervical biopsies and/or endocervical curettage in 147 (37%) of the adolescents. Two hundred fifty-three (64%) adolescents had no pathologic abnormalities on follow-up. Persistent ASC-US was identified in 65 (16%), low-grade squamous intraepithelial lesions/cervical intraepithelial neoplasia (CIN) 1 was found in 44 (11%) and high-grade squamous intraepithelial lesions/CIN 2 or 3 occurred in 36 (9%) of the adolescents. No cases of invasive carcinoma were found. Among adolescents with ASC-US, the rate of squamous intraepithelial lesions/CIN is similar to that of adults. Although the optimal management of ASC-US in adolescents is unknown, these patients warrant close follow-up. III


Successful conservative management of idiopathic fibrosing pancreatitis in children.
Idiopathic fibrosing pancreatitis, a rare cause of obstructive jaundice and abdominal pain in children, which has certain features in common with the emerging entity of autoimmune pancreatitis as described in adults, has frequently been managed surgically. We present our experience of successful conservative management of this condition in children. Three children (6-12 years; two girls, one boy) presented with a short history of abdominal pain followed by obstructive jaundice. Abdominal ultrasonographic examination in each case showed dilated intrahepatic and common bile ducts with a bulky pancreas, predominantly the head. These findings were confirmed by magnetic resonance imaging. In two cases, the diagnosis of fibrosing pancreatitis was made by exclusion after extensive investigation. The third case had a percutaneous ultrasound-guided pancreatic needle biopsy. Two patients were managed by supportive medical therapy alone, whilst the third, with symptomatic obstructive jaundice, underwent temporary endoscopic stenting of the common bile duct. Cases have been followed-up for 12-49 months. There was complete clinical and biochemical resolution of obstructive jaundice in all three cases. Plasma bilirubin concentrations decreased to normal within 3-8 weeks. Serial abdominal imaging showed a gradual resolution of biliary dilatation and abnormal pancreatic morphology with subsequent pancreatic atrophy. Two children developed steatorrhoea that responded to pancreatic enzyme supplements, and one patient developed diabetes mellitus. None of the cases needed invasive surgery for diagnosis or management. With careful radiological and biochemical assessment and monitoring, invasive surgery can be avoided in the management of fibrosing pancreatitis. The eventual outcome is no different from reported surgically treated cases.


Antimicrobial Resistance of Acinetobacter baumannii to Imipenem in Iran: A Systematic Review and Meta-Analysis.
Imipenem-resistant multi-drug resistant (IR-MDR) Acinetobacter baumannii has been emerged as a morbidity successful nosocomial pathogen throughout the world.To address imipenem being yet the most effective antimicrobial agent against A. baumannii to control outbreaks and treat patients, a systematic review and meta-analysis was performed to evaluate the prevalence of IR-MDR A. baumannii. We systematically searched Web of Science, PubMed, MEDLINE, Science Direct, EMBASE, Scopus, Cochrane Library, Google Scholar, and Iranian databases to identify studies addressing the antibiotic resistance of A. baumannii to imipenem and the frequency of MDR strains in Iran. Out of 58 articles and after a secondary screening using inclusion and exclusion criteria and on the basis of title and abstract evaluation, 51 studies were selected for analysis. The meta-analysis revealed that 55% [95% confidence interval (CI), 53.0-56.5] of A. baumannii were resistant to imipenem and 74% (95% CI, 61.3-83.9) were MDR. The MDR A. baumannii population in Iran is rapidly changing toward a growing resistance to imipenem. Our findings highlight the critical need for a comprehensive monitoring and infection control policy as well as a national susceptibility review program that evaluates IR-MDR A. baumannii isolates from various parts of Iran.


Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat.
Obesity is caused by an imbalance between energy intake and expenditure and has become a major health-care problem in western society. The central melanocortin system plays a crucial role in the regulation of feeding and energy expenditure, and functional loss of melanocortin receptor 4 (MC4R) is the most common genetic cause of human obesity. In this study, we present the first functional Mc4r knockout model in the rat, resulting from an N-ethyl-N-nitrosourea mutagenesis-induced point mutation. In vitro observations revealed impaired membrane-binding and subsequent nonfunctionality of the receptor, whereas in vivo observations showed that functional loss of MC4R increased body weight, food intake, white adipose mass, and changed substrate preference. In addition, intracerebroventricular (ICV) administration of Agouti-Related Protein(79-129) (AgRP(79-129)), an MC4R inverse agonist, or Melanotan-II (MTII), an MC4R agonist, did affect feeding behavior in wild-type rats but not in homozygous mutant rats, confirming complete loss of MC4R function in vivo. Finally, ICV administration of MTII induced excessive grooming behavior in wild-type rats, whereas this effect was absent in homozygous mutant rats, indicating that MTII-induced grooming behavior is exclusively regulated via MC4R pathways. Taken together, we expect that the MC4R rat model described here will be a valuable tool for studying monogenic obesity in humans. More specifically, the relative big size and increased cognitive capacity of rats as compared to mice will facilitate complex behavioral studies and detailed mechanistic studies regarding central function of MC4R, both of which ultimately may help to further understand the specific mechanisms that induce obesity during loss of MC4R function.