Relationship between uptake of norepinephrine by hypothalamic homogenates and the activity of brown adipose tissue.
It has previously been established that norepinephrine (NE) in the central nervous system is involved in feeding and the development of obesity. The present experiments were carried out to investigate the relationship between the uptake of NE by a crude hypothalamic homogenate and NE-mediated sympathetic activity in interscapular brown adipose tissue (IBAT). Sympathetic nervous system activity was assessed by measuring the binding of the purine nucleotide guanosine-5'-diphosphate (GDP) to mitochondria isolated from IBAT. Four situations known to alter food intake and sympathetic activity, namely, corticotropin releasing factor infusion, adrenalectomy, fenfluramine treatment and obesity due to genetic transmission were studied. In each case, [3H]NE uptake by the hypothalamic preparation and GDP binding to IBAT mitochondria were measured. A highly significant negative correlation between the uptake of NE by hypothalamic homogenates and the binding of GDP to IBAT mitochondria was obtained in both lean and obese animals. These findings are discussed with regard to the regulation of food intake and sympathetic nervous system mediated thermogenesis.


Evaluation of the efficacy of subcutaneous carbon dioxide insufflations for treating acute non specific neck pain in general practice: A sham controlled randomized trial.
Subcutaneous carbon dioxide insufflations are a safe and inexpensive treatment modality in complementary medicine and are used mainly in musculoskeletal pain and vascular conditions. However, no rigorous trial exists on their efficacy. To evaluate whether patients with acute non specific neck pain get pain free sooner, if treated with subcutaneous carbon dioxide insufflations compared to sham ultrasound. One hundred and twenty-six persons from one German general practice with acute non specific neck pain less than 7 days and a current pain intensity 40 mm on a 100 mm visual analogue scale were included into the trial. Participants received either a maximum number of nine subcutaneous carbon dioxide insufflations or a maximum number of nine sham ultrasound administered by four therapists in a randomized order, thrice weekly. Main outcome measure was time to neck pain relief during a 28 days follow-up period from baseline analyzed by intention to treat. Twenty-seven of 63 patients (43%) got neck pain free in the subcutaneous carbon dioxide insufflations group compared to 29 of 63 (46%) in the sham ultrasound group. Median time to neck pain relief was 28 days in both groups (p=.77; logrank test). Secondary analyses yielded similar results. The study indicates that subcutaneous carbon dioxide insufflations are not superior to sham ultrasound for treating patients with acute non specific neck pain. Because course of pain did not differ from the one expected from self limitation, it is likely that non specific effects played only a minor role, if any, in both interventions.


[Delusion and dreams in "Death in Venice". Thomas Mann's consequential reading of Freud in 1911].
The author shows by means of literary comparisons that in "Death in Venice" and The Magic Mountain, Mann was strongly influenced by Freud's psychoanalysis, in particular by the latter's work "Delusion and dreams in W. Jensen's 'Gradiva'."


Antitumor effect of interleukin-1 beta in the double grafted tumor system.
The antimetastatic effect of recombinant human interleukin-1 beta (rIL-1 beta) in a new experimental mouse model was studied. Intratumoral administration of IL-1 beta strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete regression of tumors and resistance to reinoculated tumor. Subsequently, the anti-metastatic effect of IL-1 beta was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with 0.2 micrograms of IL-1 beta in the right tumor on days 3, 4 and 5. IL-1 beta significantly inhibited the growth of the left, non-treated tumor. When mice received only an inoculation of Meth-A (2 X 10(5) cells) in the left flank and were injected subcutaneously with IL-1 beta into the right flank on day 3 (single tumor system), there was no inhibition of the growth of the left, non-treated tumor. These findings suggest that intratumoral IL-1 beta immunotherapy in one region has an effect on tumor growth in another region. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of IL-1 beta. Adoptive transfer of the immunized spleen cells caused the complete regression of Meth-A tumors. These results suggest that intratumoral administration of IL-1 beta might induce cytotoxic cells in the left non-treated tumor of the double grafted tumor system and bring about the regression of metastatic tumors.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of bovine heparin-binding neurotrophic factor (HBNF): assignment of disulfide bonds.
The topology of the disulfides in native heparin-binding neurotrophic factor (HBNF) isolated from bovine brain was studied by proteolytic digestion using trypsin, Asp-N endoproteinase and chymotrypsin and peptide mapping. Disulfide-linked peptides were identified by automated Edman degradation. It has been shown that there are disulfide bonds between Cys15-Cys44, Cys23-Cys53, Cys30-Cys57, Cys67-Cys99 and Cys77-Cys109.


[Production of extracellular proteinases (protein C activators in blood plasma) by the micromycete Aspergillus ochraceus during submerged and solid-state cultivation].
The conditions for the submerged and solid-state cultivation of the micromycete Aspergillus ochraceus VKM F-4104D, producing extracellular proteinases that activate protein C in human blood plasma, were optimized. It is shown that the protein C-activating activity of the micromycete in a solid-state culture was 1.5-3.5 times higher than in a submerged culture (as calculated per milliliter of culture medium). Among the extracellular proteins secreted by A. ochraceus VKM F-4104D during submerged and solid-state cultivation, a protein C-activating proteinase with a pI of 6.0-6.3 was identified.


Ocular adverse events following vaccination: overview and update.
The Food and Drug Administration has licensed, approved, and expanded guidelines for dozens of vaccines since 2010. Although advancements in biotechnology have made vaccines more effective and safer, none are completely free from adverse effects. Many vaccines have been implicated in causing ocular adverse events based on the temporal association of exposure and putative complication. Determination of causality is difficult. We provide an overview of vaccine side effects and also examine the English literature and the Vaccine Adverse Events Reporting System (VAERS) from 2010 through 2020 for vaccine-implicated ocular adverse events. While reactions of eyelids and conjunctiva are commonly reported, the most frequently implicated serious adverse events are optic neuritis and various patterns of intraocular inflammation. Live attenuated vaccines have the potential to cause ocular infection from vaccine-strain organisms, particularly in those immunosuppressed. While postmarketing registries for suspect vaccination adverse events, such as VAERS, are unable to determine causal associations, they are a mainstay in signaling suspected trends that require investigation. The majority of probable and possible serious ocular adverse effects are distinctly uncommon.


Measurement of Genetic Mobility Using a Transposon-Based Marker System in Sorghum.
Transposable elements (TEs) are ubiquitous repetitive components of eukaryotic organisms that show mobility in the genome against diverse stresses. TEs contribute considerably to the size, structure, and plasticity of genomes and also play an active role in genome evolution by helping their hosts adapt to novel conditions by conferring useful characteristics. We developed a simple and rapid method for investigation of genetic mobility and diversity among TEs in combination with a target region amplification polymorphism (TE-TRAP) marker system in gamma-irradiated sorghum mutants. The TE-TRAP marker system reveals a high level of genetic diversity, which provides a useful marker resource for genetic mobility research.


Protopanaxatriol activates EGFR and HER2 to strengthen the molecules of skin protection in human keratinocytes.
Protopanaxatriol (PPT) is an important ginsenoside produced by ginseng, a tonic plant used in many areas. PPT has beneficial effects against many disease states including inflammation, diabetes, and cancer. However, PPT's protective effects on skin integrity have been rarely studied. Previously, we reported that PPT can maintain skin moisture through activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways. However, the cellular targets for enhancing skin moisturizing effects via PPT are still unknown. We wanted to identify the upstream targets of PPT on upregulating moisturizing factor (HAS-2) expression. We investigated which upstream proteins can be directly stimulated by PPT to modulate NF-κB, MAPKs and other signaling cascades. Then, the targeted proteins were overexpressed to check the relationship with HAS-2. Next, the cellular thermal shift assay (CETSA) was conducted to check the relationship between targeted proteins and PPT. A human keratinocyte HaCaT were employed to measure the levels of moisturizing factors and the signaling proteins activated by PPT. Transfection conditions were established with DNA constructs expressing epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and their mutants prepared by site-directed mutagenesis. Further investigation on molecular mechanisms was conducted by RT-PCR, luciferase reporter gene assay, CETSA, or Western blot. We found that PPT can activate the phosphorylation of EGFR and HER2. These stimulations caused Src phosphorylation, which resulted in the activation of phosphoinositide 3-kinases (PI3K)/pyruvate dehydrogenase kinase 1 (PDK1)/protein kinase B (AKT)/NF-κB and MAPKs signaling cascades. Additionally, EGFR and HER2 activation resulted in phosphorylation of signal transducer and activator of transcription 3 (STAT3) and calcium/calmodulin-dependent protein kinase II (CaMKII). This induced the AMP-activated protein kinase alpha (AMPKα) signaling pathway. Additionally, PPT blocked peroxisome proliferator activated receptor gamma (PPARγ), which also contributed to the phosphorylation of Src. Overall, we first found that PPT offers excellent protection of the skin barrier and hydrogen supply in keratinocytes. Moreover, growth factor receptors such as EGFR and HER2 were revealed to be central enzymes to be directly targeted by PPT. These results suggest a potentially valuable role as a cosmetic ingredient.


Clostridium infection in a knee extensor mechanism allograft: case report and review.
An unusual case of Clostridium perfringens infection after an allograft reconstruction of an extensor mechanism in a multiply revised total knee arthroplasty is reported. The case occurred in an elderly patient with an underlying bleeding dyscrasia who had previously undergone two revision total knee arthroplasties. The patient was treated by open irrigation, debridement, removal of allograft and prosthesis, intravenous antibiotics, and implantation of an antibiotic impregnated cement spacer utilizing an intramedullary rod.


Elastase: production by ringworm fungi.
Isolants of nine species of Trichophyton, one of Epidermophyton, and four of Microsporum were assayed for elastase activity. The species or isolants with elastase activity were obtained from patients with inflammatory ring-worm infection. In Nannizzia fulva (M. fulvum), plus-mating-type strains were elastase-positive and minus-mating-type strains elastase-negative. A genetic study of mating type and elastase activity indicated a monogenic basis for both mating type and elastase activity.


Analysis of miRNA Expression Using Digital PCR and the QuantStudio™ 3D Digital PCR System.
miRNAs are short, single-stranded RNA molecules that function as posttranscriptional regulators of gene expression. miRNAs represent ideal biomarkers since they can also circulate in the bloodstream as well as in other biological fluids such as urine, saliva, and cerebrospinal fluid.miRNAs play an important role in the regulation of immune cells including cytotoxic T-lymphocytes. Circulating miRNAs can be analyzed by Real-Time PCR or microarray profiling; however data normalization represents still an unsolved problem due to the lack of widely validated house-keeping miRNAs candidates.Digital PCR (dPCR) is an end-point PCR method that is used for absolute quantification. In this chapter we will describe the applications of Digital PCR for the analysis of miRNAs that can influence immune response in serum samples and we will report a specific protocol that can be used to analyze miRNAs using the QuantStudio™ 3D Digital PCR System. The advantage of this method consists in the possibility to highlight weaker differences in miRNA circulating molecules that can be useful to monitor CTLs behavior in pathological conditions or after therapeutic intervention.


Common features of light-evoked amacrine cell responses in vertebrate retina.
The light-evoked electrical responses of a large number of amacrine cells in the roach retina have been observed by intracellular recording. Examination of response profiles suggests that amacrine cell responses possess a number of common features: combinations of sustained and transient components, light-dependent membrane noise and oscillations, afterpotentials. From these and other observations taken together, a unified view of light-evoked amacrine cell responses is presented, whereby response profiles are thought to reflect synaptic organizations rather than differences in inherent membrane properties.


Hepatitis E virus seroprevalence among adults, Germany.
We assessed hepatitis E virus (HEV) antibody seroprevalence in a sample of the adult population in Germany. Overall HEV IgG prevalence was 16.8% (95% CI 15.6%-17.9%) and increased with age, leveling off at >60 years of age. HEV is endemic in Germany, and the lifetime risk for exposure is high.


Left ventricular geometry and electrocardiographic criteria in assessing left ventricular hypertrophy in sickle cell anemia patients.
Left ventricular hypertrophy (LVH) is recognized as a cardiovascular risk factor and is a known consequence of sickle cell anemia (SCA). Abnormal left ventricular geometric patterns have been described but the determinants have not been well elucidated. Electrocardiography (ECG) and Echocardiography (ECHO) was done on subjects with SCA and hemoglobin A(HBA). Those with systemic hypertension were excluded. Voltages, durations, and intervals were measured as appropriate and recorded in a standard proforma. Analysis was made using a standard statistical software. Eighty four people with SCA and 91 with HBA were recruited as cases and controls respectively. Subjects with SCA have more abnormal LV geometric patterns than those with HBA(p=0.000). Eccentric LVH(p=0.000) was more in SCA subjects while concentric LVH(p=0.054) and concentric remodeling(p=0.319) were not. Forty-one and fifty-two subjects with SCA and HBA respectively did ECGs. . Subjects with eccentric LVH had lower hip circumference, higher left atrial diameter, right atrial area, higher sokolow-lyon voltage sum, stroke volume and cardiac output. The Sokolow-Lyon voltage criteria at the traditional cut off point was not different between those with and without eccentric LVH. However, Sokolow-Lyon voltage criteria at a cut-off of ≥4.7mV detected eccentric LVH with a sensitivity of 60% and specificity of 83.3%.While Sokolow-Lyon voltage sum, stroke volume, right atrial area, and left atrial diameter correlated positively, pulse rate and hip circumference correlated inversely with eccentric LVH. Sokolow Lyon voltage sum was the independent determinant of eccentric LVH in this study. Sickle cell anemia predisposes to abnormal LV geometric patterns, especially eccentric LVH. There may be a need to review the electrocardiographic cut off points for defining eccentric LVH in the SCA populace.


The clavipectoral osteomyocutaneous free flap.
Microvascular free tissue transfer has revolutionized head and neck reconstruction and currently is considered the most successful and reliable method of primary oromandibular reconstruction. This study was designed to assess the feasibility of full thickness free vascularized transfer of the clavicle based on the clavicular branch of the thoracoacromial artery and the soft tissue component associated with the thoracoacromial axis. Forty dissections of the pectoral region were performed on 26 cadavers. The anatomic relations of the region and the thoracoacromial arterial and venous systems were documented in detail. Selective ink injections of the thoracoacromial arterial branches were also performed on fresh cadavers. The clavicle was supplied mainly by the clavicular artery (medial three quarters), with minor contribution from the deltoid artery (lateral quarter). An average of 16.1 cm (range of 12 to 20 cm) was obtained with total clavicular harvest and the clavicle had sufficient width and height to support dental implants. Two soft tissue donor sites were associated with the thoracoacromial artery: the sternocostal head of the pectoralis major muscle, with the overlying skin supplied by the pectoral artery, and the clavicular head of the pectoralis major muscle, with the overlying skin supplied by the deltoid and clavicular arteries. Sensory innervation of the upper chest was supplied through the supraclavicular nerves, whereas the lateral pectoral nerve supplied motor innervation to both heads of the pectoralis major muscle. The anatomy of the clavipectoral donor site and the first case of full thickness free clavicular transfer for mandibular reconstruction in the English literature are presented. The donor site is an excellent source of well vascularized, thin, pliable, hairless, potentially innervated (motor and sensory) soft tissue, along with up to 20 cm of clavicular bone. The surgical anatomy is familiar to the head and neck surgeon. The harvesting does not require repositioning of the patient and is amenable to a two-team, simultaneous approach. The functional and cosmetic donor site morbidity is minimal even with clavicular harvest. The major disadvantage of this flap is the relatively short pedicle. The authors conclude that the thoracoacromial system provides a free flap with osseous and soft tissue components that are well suited for oromandibular reconstruction.


Coronary vasodilation by nitrates is not mediated by the prostaglandin system: a quantitative cineangiographic study.
The possible role of prostaglandins in mediating large coronary artery vasodilation by nitrates was investigated by quantitative magnification coronary angiography. The effects of aspirin (1 g systemically and 100 mg intracoronary) in preventing large coronary artery vasodilation induced by intracoronary isosorbide dinitrate was investigated in 16 patients. Of these, 5 received 0.3 mg (Group 1A) and 11 received 3 mg (Group 1B) intracoronary isosorbide dinitrate, before and 15 minutes after aspirin. Relative to control, 0.3 mg isosorbide dinitrate induced a 19 +/- 9% (mean +/- SD) (p less than 0.01) and 19.5 +/- 11% (p less than 0.01) increase in coronary diameter before and after aspirin, respectively (p = NS). Changes after 3 mg isosorbide were 23 +/- 12% (p less than 0.01) and 26.5 +/- 14% (p less than 0.01), respectively, before and after aspirin (p = NS). In 10 additional patients (Group 2), the effect of the same dose of aspirin on rest coronary artery tone was assessed: changes relative to control were 0.9 +/- 5.5% (p = NS) minutes after aspirin. The intracoronary administration of 3 mg isosorbide dinitrate produced a 24.7 +/- 11% increase in coronary diameter (p = NS versus pre- and postaspirin isosorbide in Group 1B). Urinary 6-ketoprostaglandin-F1 alpha values in urine samples collected in the 8 hours before and the 8 hours after the study in five patients in Group 1B and five patients of Group 2, revealed a 36 +/- 14% (mean +/- SD) reduction in excretion of prostacyclin (p less than 0.01). These data rule out a role for prostaglandins both in mediating dilation of large coronary arteries by nitrates and in affecting their vascular tone at rest.


A case report on death from acute bacterial cholangitis accompanied by von Meyenburg complexes: Use of 16S rRNA gene sequencing to identify pathogenic microbes from postmortem formalin-fixed, paraffin-embedded tissue.
In some cases, autopsy is the first opportunity to find a previously unrecognized critical infection. Pathogens are identified by various methods, such as microscopic examination, special stains, culture tests, and immunohistochemistry. Here, we report a case of 16S ribosomal RNA (rRNA) gene sequencing using a postmortem formalin-fixed, paraffin-embedded (FFPE) tissue, which was useful for identifying pathogenic microbes. Autopsy was performed on an 87-year-old man who had chronic renal failure and had developed sepsis from a central venous catheter infection 10 days before his death. Prior to these events, von Meyenburg complexes (VMCs) were also found during regular checkups. Postmortem microscopic examination revealed acute purulent cholangitis with numerous microabscesses, accompanied by VMCs. Gram-negative rods were observed in some microabscesses, which were considered causative pathogens. 16S rRNA gene sequencing using postmortem FFPE tissue. Pseudomonas aeruginosa was identified, different from the one detected in the central venous catheter culture while alive. 16S rRNA gene sequencing is a useful tool for identifying pathogenic microbes in postmortem FFPE tissues. This technique may be useful for amplicon sizes of approximately 100 bp or less.


Trends in respiratory management of transferred very preterm infants in the last two decades.
Among infants needing urgent transfer after birth, very preterm infants are a high-risk sub-group requiring special attention. This study aimed to assess trends in early respiratory management in a large series of very preterm infants undergoing postnatal transfer. Trends in patient characteristics and early respiratory management were assessed in 798 very preterm infants who were transferred by the Eastern Veneto Neonatal Emergency Transport Service in 2000-2019. Trends were analyzed using joinpoint regression analysis and summarized as annual percentage changes (APCs). Proportion of neonates with birth weight less than 1 kg decreased from 33% to 16% (APC -3.82%). Use of nasal-continuous-positive-airway pressure increased (at call: APC 15.39%; during transfer: APC 15.60%), while use of self-inflating bag (at call: APC -12.09%), oxygen therapy (at call: APC -13.00%; during transfer: APC -23.77%) and mechanical ventilation (at call: APC -2.71%; during transfer: APC -2.99%) decreased. Use of oxygen concentrations at 21% increased (at call: APC 6.26%; during transfer: APC 7.14%), while oxygen concentrations above 40% decreased (at call: APC -5.73%; at transfer APC -8.89%). Surfactant administration at call increased (APC 3%-10%), while surfactant administration when arriving at referring hospital remained around 7-11% (APC 2.55%). Relevant trends toward "gentle" approaches in early respiratory management of very preterm infants undergoing postnatal transfer occurred during the last twenty years. In addition, the proportion of transferred extremely low birth weight infants halved. Clinicians and stakeholders should consider such information when allocating assets to both hospitals and transfer services and planning regional perinatal programs.


The effect of vitiligo on sexual relationships.
To study the effect of vitiligo on interference with sexual relationships, we surveyed 158 patients by questionnaire. Although a majority of patients reported a negative impact on sexual relationships, most patients felt embarrassment when showing their body or meeting strangers. The majority of patients who reported a negative impact on sexual relationships attributed the problems to their embarrassment. Those who were particularly affected were those with low self-esteem, men, those to whom appearance is important, and single persons. Dermatologists should be especially alert to the effects of disfigurement and should attempt to assist patients with this problem.


Vancomycin powder for the prevention of surgical site infection in posterior elective spinal surgery.
To assess the effectiveness and safety of vancomycin powder as surgical site infection (SSI) prophylaxis in posterior bilateral elective spinal surgery. Single-center quasi-experimental pre and postintervention comparative cohort study. The post-intervention group received standard intravenous antibiotic prophylaxis plus 1g of vancomycin powder into the surgical field before wound closure, and the pre-intervention group only the intravenous prophylaxis. 150 patients were included in each group. Twelve SSI (7 superficial and 5 deep) occurred in the post-intervention group and 16 SSI (7 superficial and 9 deep) in the pre-intervention group. The risk of deep SSI decreased from 6.0% to 3.3% (OR 0,54, 95%CI 0.17-1.65, p=0.411) with vancomycin powder. The percentage of deep SSI due to gram negative-positive germs were 80%-20% and 33%-67% for the post- and pre-intervention groups, respectively (p=0.265). No local or systemic adverse effects occurred attributable to vancomycin powder. In posterior elective spinal surgery, prophylaxis with vancomycin powder did not result in a significantly reduced incidence of superficial and deep SSI. There was a trend towards a higher incidence of deep SSI caused by gram negative microorganisms among those treated with vancomycin.


Factors associated with intention to vaccinate a daughter against HPV: a statewide survey in Alabama.
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Adolescent and young adults aged 15-24 were estimated to account for three quarters of new infections in 2000. Two HPV vaccines are currently available. The vaccine is recommended for girls aged 11-12 years. Previous research has indicated that African-American and Asian-American parents are less likely than Caucasians to vaccinate their daughters. This investigation examines the relationship between demographic, medical, and behavioral risk factors for HPV vaccine acceptability among Alabama residents. The cross-sectional survey was conducted using random digit dialing. Eligible participants were female caregivers of adolescent girls between the ages of 10 and 14 years. Factors related to intention to vaccinate a daughter within the next six months were examined using chi-square and logistic regression. Caregivers who were informed about HPV vaccination from a health care provider were more likely to intend to vaccinate their daughter within the next six months compared with caregivers who did not report this source of information (OR = 3.59, 95% CI = 1.52, 8.45). Race, education, county of residence, child's age, religious attendance, knowledge and history of HPV, perceived susceptibility, and severity of infection were not significantly related to intention to vaccinate against HPV. Caregivers who were informed of the vaccine by their health care provider were more likely to vaccinate their adolescent daughters. Provider attitudes and caregiver education is an essential link to improvement of HPV vaccination uptake in Alabama.


Determination of lysozyme activity at low levels with emphasis on the milk enzyme.
A method is described for the determination of lysozyme (muramidase) activity, whereby sensitivity is maximized by incubation of the reaction mixture (sample, buffer, and substrate (Micrococcus luteus] over an extended period. This approach is made feasible by exploiting our observation that the lytic reaction follows simple kinetic order during this time (e.g., 700 min for bovine lysozyme and 960 min for the eggwhite enzyme at low concentrations). After this period, the reaction rates diminish, indicating biphasic behavior, and eventually become negligible. The kinetic order may vary with both the type of lysozyme and the buffer system used. The limit of detection for bovine milk lysozyme is 100 pg/ml reaction mixture, equivalent to 6 ng/ml milk, for a 50-microliters sample (with reference to hen eggwhite lysozyme). With these limits, the method has proven valuable in our comparative studies, particularly for low levels of activity in bovine milk, but also in secretions and tissue extracts from various other eutherian, metatherian, and prototherian mammals. The method may also be applied to investigation of structure and function in modified forms of the enzyme.


Genome sequence analysis of multidrug-resistant Mycobacterium tuberculosis from Malaysia.
Mycobacterium tuberculosis (MTB) is commonly used as a model to study pathogenicity and multiple drug resistance in bacteria. These MTB characteristics are highly dependent on the evolution and phylogeography of the bacterium. In this paper, we describe 15 new genomes of multidrug-resistant MTB (MDRTB) from Malaysia. The assessments and annotations on the genome assemblies suggest that strain differences are due to lineages and horizontal gene transfer during the course of evolution. The genomes show mutations listed in current drug resistance databases and global MTB collections. This genome data will augment existing information available for comparative genomic studies to understand MTB drug resistance mechanisms and evolution.


Association between Walking Pace and Diabetes: Findings from the Chilean National Health Survey 2016-2017.
Walking pace is a well-known indicator of physical capability, but it is also a strong predictor of type 2 diabetes (T2D). However, there is a lack of evidence on the association between walking pace and T2D, specifically, within developing countries such as Chile. To investigate the association between self-reported walking pace and T2D in the Chilean adult population. 5520 Chilean participants (aged 15 to 90 years, 52.1% women) from the Chilean National Health Survey 2016-2017 were included in this cross-sectional study. Both walking pace (slow, average, and brisk) and diabetes data were collected through self-reported methods. Fasting blood glucose (reported in mg/dl) and glycosylated haemoglobin A (HbA1c) scores were determined via blood exams. In the unadjusted model, and compared to people who reported a slow walking pace, those with average and brisk walking pace had lower blood glucose levels (β = -7.74 mg/dL (95% CI: -11.08 to -4.40) and β = -11.05 mg/dL (95% CI: -14.36 to -7.75), respectively) and lower HbA1c (β = -0.34% (95% CI: -0.57 to -0.11) and β= -0.72% (95% CI: -0.94 to -0.49)), respectively. After adjusting for sociodemographic, Body Mass Index and lifestyle factors, the association between glycaemia and HbA1c remained only for brisk walkers. Both the average and brisk walker categories had lower odds of T2D (OR: 0.59 (95% CI: 0.41 to 0.84) and (OR 0.48 (95% CI: 0.30 to 0.79), respectively). Brisk walkers were associated with lower blood glucose and HbA1c levels. Moreover, average to brisk walking pace also showed a lower risk for T2D.


Religious coping and quality of life among individuals living with schizophrenia.
This study investigated the relationship between positive and negative religious coping and quality of life among outpatients with schizophrenia. Interviews were conducted with 63 adults in the southeastern United States. Religious coping was measured by the 14-item RCOPE and quality of life by the World Health Organization Quality of Life–BREF. Data were examined via descriptive bivariate statistics and controlled analyses. Most participants reported participation in private religious or spiritual activities (91%) and participation in public religious services or activities (68%). Positive religious coping was related to the quality-of-life facet of psychological health (r=.28, p=.03). Negative religious coping and quality of life were inversely related (r=–.30, p=.02). Positive religious coping was associated with psychological health in the reduced univariate general linear model (B=.72, p=.03, adjusted R(2)=.08). Greater awareness of the importance of religion in this population may improve cultural competence in treatment and community support.


Extra-Virgin Olive Oil Improves Depression Symptoms Without Affecting Salivary Cortisol and Brain-Derived Neurotrophic Factor in Patients With Major Depression: A Double-Blind Randomized Controlled Trial.
Many patients with depression are reluctant to take psychiatric medications. Hence, complementary therapies such as nutritional considerations could be advantageous. The antidepressant potential of olive oil has been proved in observational studies. The effect of extra-virgin olive oil (EVOO) on depression symptoms and cortisol and brain-derived neurotrophic factor (BDNF) levels in patients with depression was examined. This was a double-blind randomized controlled trial conducted on 73 patients suffering from major depressive disorder in Shiraz, Iran, in 2016. The patients were randomly assigned to intervention (EVOO) and control (sunflower oil) groups and consumed 25 mL/d of the corresponding oil for 52 days. Depression symptoms were assessed by Beck Depression Inventory-II (BDI-II) and 7-item Hamilton Depression Rating Scale (HAMD-7). Salivary cortisol levels were determined immediately after awakening and 30 minutes later. Cortisol awakening response and the area under the curve with respect to ground and increase were computed. Serum BDNF concentrations were also measured. Statistical analysis was conducted based on intention-to-treat and per-protocol approaches. Within-group changes were examined with repeated measures (for BDI-II and HAMD-7) and with paired t test (for other variables). Between-group comparisons were performed with analysis of covariance after adjustment for confounding factors. In intention-to-treat analysis, HAMD-7 score was the only variable with significant changes within and between groups, the latter as a greater decline in EVOO group (P = .001). BDI-II score did not show significant change in either group but the between-group comparison revealed a significant difference (P = .021). EVOO showed antidepressant effect in severely depressed patients (P = .017 for BDI-II and 0.008 for HAMD-7) but not in mild/moderate depression category. Serum BDNF concentrations, salivary cortisol levels at immediately after awakening (T0) and 30 minutes later, cortisol awakening response, the area under the curve with respect to ground and increase did not change within or between groups. Results of per-protocol analysis were not different. The results of this study suggested beneficial effects of EVOO on depression symptoms in patients with severe depression but not in those with mild to moderate depression. The effects were significant from both statistical and clinical points of view.


Aortic allograft infection risk.
Intrinsic risk of infection of cryopreserved allograft aortic root replacements remains poorly understood despite their long history of use. The objective of this study was to determine this intrinsic risk of allograft infection and its risk factors when allografts are implanted for both nonendocarditis indications and infective endocarditis. From January 1987 to January 2017, 2042 patients received 2110 allograft aortic valves at a quaternary medical center, 1124 (53%) for nonendocarditis indications and 986 (47%) for endocarditis indications (670 [68%] prosthetic valve endocarditis). Staphylococcus aureus caused 193 of 949 cases of endocarditis (20%), 71 (7.3%) in persons who injected drugs. Periodic surveillance and cross-sectional follow-up achieved 85% of possible follow-up time. The primary end point was allograft infection in patients with nonendocarditis and endocarditis indications. Risk factors were identified by hazard function decomposition and machine learning. During follow-up, 30 allografts (26 explanted) became infected in patients in the nonendocarditis group and 49 (41 explanted) in patients with endocarditis. At 20 years, the probability of allograft infection was 5.6% in patients in the nonendocarditis group and 14% in patients with endocarditis. Risk factors for allograft infection in patients in the nonendocarditis group were younger patient age and older donor age. Risk factors for allograft infection in patients with endocarditis were earlier implant year, injection drug use, and younger age. In patients with endocarditis, 18% of allograft infections were caused by the original organism. The low infection rates, both in patients without and with endocarditis, support continued use of allografts in the modern era, in particular for the treatment of invasive endocarditis of the aortic root.


Single Needle All-Inside Technique for Lateral Meniscus Repair at Popliteal Hiatus Area: Safe, Effective, and Time-Saving.
The lateral meniscus tear at the popliteal hiatus area is a tricky problem in clinical treatment due to the difficulty of preoperative diagnosis, narrow space for operation, lack of capsular attachments, and risk of vascular injuries. This article introduces an arthroscopic single-needle, all-inside technique suitable for repairing longitudinal and horizontal lateral meniscus tears at the popliteus tendon hiatus area. We believe this technique is safe, effective, economical and reproducible.


Differences in Psychometric Properties of Clinician- and Patient-Reported Outcome Measures for Atopic Dermatitis by Race and Skin Tone: A Systematic Review.
The psychometric validity and reliability of widely used atopic dermatitis (AD) outcome measures across different races and ethnicities are unclear. We describe the rates of reporting race, ethnicity, and skin tone in studies testing the psychometric properties of AD outcome measures and compare the psychometric analyses across race, ethnicity, and skin tone. We systematically reviewed MEDLINE and EMBASE for studies reporting psychometric properties of clinician-reported or patient-reported outcome measures in AD (International Prospective Register of Systematic Reviews: CRD42021239614). Overall, 16,100 nonduplicate articles were screened; 165 met inclusion criteria. Race and/or ethnicity were reported in 55 (33.3%) studies; of those, race was assessed by self-report in 10 studies (6.1%) or was unspecified in 45 (27.3%). A total of 16 studies (9.7%) evaluated psychometric property differences by race, and only five (4.4%) of those did not recognize it as a limitation. Properties assessed across race, ethnicity, or skin tone were differential item functioning, convergent validity feasibility, inter-rater reliability, intrarater reliability, test‒retest reliability, and known-groups validity. Multiple instruments demonstrated performance differences across ethnoracial groups. This review highlights the paucity of race/ethnicity consideration for psychometric property testing in AD outcome measurement instruments. More AD outcomes instruments should be validated in diverse populations.


Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-up: AUA Guideline: Part II.
This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions. In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned strength-rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses <2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency. AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.


Highly selective L-threonine 3-dehydrogenase from Cupriavidus necator and its use in determination of L-threonine.
l-Threonine level in blood plasma is a biomarker of some diseases and nitrogen imbalance in the body. The determination of l-threonine is interesting and is required for diagnosis and management of inherited metabolic disorder. This is the first report of the specific enzymatic determination of l-threonine by a newly discovered l-threonine 3-dehydrogenase (ThrDH, EC 22.214.171.124) from Cupriavidus necator NBRC 102504. ThrDH, a key enzyme in l-threonine catabolism in microorganisms and animals, catalyzes the NAD(+)-dependent oxidation of l-threonine to 2-amino-3-oxobutyrate. ThrDH from C. necator was purified to homogeneity and fully characterized. l-Threonine and dl-2-amino-3-hydroxyvalerate are the only substrates for ThrDH among other l-amino acids, alcohols, and amino alcohols. The primary amino acid structure of ThrDH belongs to the extended short-chain alcohol dehydrogenase superfamily and is related to GDP-mannose-3',5'-epimerase (GME) from Arabidopsis thaliana. Both enzymes have a glycine-rich NAD(+)-binding domain at the N terminal and conserved catalytic triad of YxxxK residues, but substrate-binding residues of GME were not found in the ThrDH sequence. ThrDH significantly differs from known bacterial and archaea ThrDHs that belong to zinc-binding medium chain alcohol dehydrogenase because of low sequence similarity and the lack of a zinc-binding domain in the sequence. A specific, quantitative, and sensitive enzymatic endpoint method for l-threonine determination was developed by using a ThrDH microplate assay. The assay was successfully applied for determination of l-threonine in human serum and plasma. Our specific determination is simple, convenient, inexpensive, accurate, and suitable for mass screening determination of l-threonine in a number of samples.


Inference of transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection.
Deregulation of transcription factors (TFs) is an important driver of tumorigenesis, but non-invasive assays for assessing transcription factor activity are lacking. Here we develop and validate a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyze whole genome sequencing data for >1,000 cell-free DNA samples from cancer patients and healthy controls using a bioinformatics pipeline developed by us that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observe patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of detection of early-stage colorectal carcinomas. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable to clinical analysis.


Potentiation of calcitonin by corticosteroids during the treatment of the hypercalcaemia of malignancy.
Some patients treated for the hypercalcaemia of malignancy develop renal tubular resistance to the effects of calcitonin which is independent of concurrent changes in sodium excretion. This type of resistance can be overcome by the addition of corticosteroids. In other patients apparent renal resistance to calcitonin is a consequence of reduced sodium excretion and is unaffected by corticosteroids.


Mortality in the neonatal intensive care unit: improving the accuracy of death reporting.
Death certificates commonly contain errors, which hinders understanding of infant mortality. We, therefore, undertook a quality improvement (QI) initiative to improve death reporting in our neonatal intensive care unit (NICU). After our baseline assessment (January 1, 2015 to June 30, 2017), we implemented our QI initiatives using Plan, Do, Study, Act (PDSA) tests of change. We prospectively reviewed death certificates (July 1, 2017 to December 31, 2019) to evaluate the impact of our interventions. The overall proportion of incorrect death certificates significantly decreased from 71 to 22% with special cause variation noted after the second PDSA cycle. The most common errors involved inaccurate or incomplete reporting of prematurity and errors in the sequence of events. Through a series of PDSA cycles focused on formal provider education and ongoing review, we significantly reduced inaccurate death reporting. These interventions are generalizable across NICUs and important to improve public health reporting accuracy.


Molecular analysis of mucopolysaccharidosis IVA (Morquio A) in Spain.
Mucopolysaccharidosis type IVA (Morquio A) is an inherited metabolic disease with autosomal recessive inheritance. The pathology is due to a deficient activity of N-acetylgalactosamine-6-sulfate-sulfatase, which is involved in the degradation of keratan sulfate and chondroitin-6-sulfate. To date more than 150 mutations have been described in the GALNS gene in different populations. The aim of this study was to analyze the mutations and polymorphisms in Spain in order to know the epidemiology of our population and also to offer genetic counseling to affected families. We found 30 mutant alleles in the 15 families analyzed completing all the genotypes. Most of the mutations that we found were missense mutations, six of which were novel: p.S74F, p.E121D, p.Y254C, p.E260K, p.T394P and p.N495Y; we also found a small deletion (c.1142delC) and a probable deep intronic mutation that causes the loss of exon 5 (c.423_566del) found in cDNA. Both mutations are described in this study for the first time. We also identified 20 polymorphisms previously reported and 2 novel ones: (c.633+222T/C and c.898+25C>G). In conclusion, we have identified the mutations responsible for Mucopolysaccharidosis IV A in Spain. We found great allelic heterogeneity, as occurs in other populations, which hinders the establishment of genotype-phenotype correlations in Spain. This study has been very useful for genetic counseling to the affected families.


Molecular evidence for a viral etiology of human CNS tumors.
The newer methods of molecular virology, including molecular hybridization and the "simultaneous detection test," were used to examine human brain tumors for evidence of RNA tumor viruses. It was found that they contained 70S RNA and RNA-directed DNA polymerase, both encapsulated in a particle possessing a density of 1.17 g/ml. These particles therefore satisfy the three diagnostic features that characterize the animal RNA tumor viruses. Of 26 of the most malignant (glioblastoma and medullo blastoma) brain tumors examined, 24 (92%) contained these virus-like entities. The possible usefulness of these particles as aids in diagnosis and monitoring therapy is briefly discussed.


[Reflex changes in efferent sympathetic nerve activities of visceral organs during PEEP loading in anesthetized dogs].
To study the effects of PEEP 0.98 kPa (1 kPa = 10.2 cmH2O) on the sympathetic nerve activities of visceral organs in anesthetized dogs with intact neuraxis or with vagotomy. Renal (RNA), cardiac (CNA), hepatic (HNA) and adrenal gland (AdNA) sympathetic nerve activities were recorded. Mean blood pressure (MBP), central venous pressure (CVP), left atrial pressure (LAP) and airway pressure (AWP) were also measured. AdNA significantly decreased, but RNA, CNA and HNA had a tendency toward decrease during PEEP loading in the intact dogs. However, vagotomy reversed the changes in all nerve activities in the intact dogs. CVP, LAP and AWP significantly increased, while MBP significantly decreased during PEEP loading. The results indicated that PEEP loading caused sympathoinhibition in the adrenal gland, kidney, heart and liver, which were mediated by activation of cardiopulmonary baroreceptor.


Coronary artery calcification is associated with mortality independent of pulmonary embolism severity: a retrospective cohort study.
To assess coronary artery calcification (CAC) and vascular calcification in patients with pulmonary embolism (PE) and correlate this with mortality. PE severity was quantified using computed tomography pulmonary angiography (CTPA) in 400 consecutive cases using the modified Miller score (1-5, mild; 6-11, moderate; 12-16, severe). Right ventricle strain was assessed using the right/left ventricle diameter (RV/LV) ratio. CAC score (CACS) was assessed using a four-point scale (CACS mild 1-3, moderate 4-8, severe 9-12) for each vessel and summed to give the total CACS. Follow-up for mortality was obtained at 3 years. PE severity was classified as mild in 48%, moderate in 21%, and severe in 32% of cases. The median modified Miller score was 6 (Interquartile range [IQR] 2, 14) and median total CACS was 2 (IQR 0, 7). All-cause mortality occurred in 128 (32%) patients. Patients with CAC were three times more likely to die than patients without CAC (Hazard ratio [HR] 2.96; 95% CI 1.84, 4.77; p<0.001), and patients with severe CAC were at the highest risk (HR 4.62; 95% CI 2.73, 7.83, p<0.001). Gender, modified Miller score and RV/LV ratio were not predictive of mortality. In multivariate analysis both CACS and age were independent predictors of 3-year all-cause mortality. Of the patients with CAC who died, the presence of coronary artery disease was only documented in 34 (32%). CACS is an independent predictor of all-cause mortality in patients with PE, and has important implications for subsequent patient management.


Is release of the posterior lamella enough? A cadaveric exploration of posterior component separation techniques.
As posterior component separation techniques continue to gain popularity there is uncertainty regarding the degree of fascial advancement afforded by the various techniques. Our study seeks to compare the degree anterior rectus sheath translation seen in full transversus abdominus release compared to simple release of the posterior lamella of the rectus sheath. Ten hemi-abdomens in five fresh cadavers were dissected. One hemi-abdomen underwent external oblique release. The contralateral hemi-abdomen underwent retrorectus dissection and initial release of the internal lamella of the internal oblique, followed by full transversus abdominus release. A 4 kg weight was suspended from the fascia and excursion was measured after 1) external oblique separation, 2) posterior lamella of the internal oblique separation, and 3) transversus abdominis separation. Average unilateral hemifascial translation after release of the external oblique provided an average unilateral hemi-fascial translation of 3.38 cm (+/- 0.69). Release of the posterior lamella of the internal oblique provided 3.98 cm (+/- 0.94). After transversus release the average translation increased to 4.31 cm (+/- 0.89). In this cadaveric study, the majority (92%) of fascial advancement afforded by posterior component separation was achieved by an intermediate step in the transversus abdominus release operation: division of the posterior lamella of the internal oblique.


Patient safety in nursing technician training.
to analyze the contents on patient safety in the training of nursing technicians. a documentary study, conducted in three technical nursing courses at a public university in northeastern Brazil, based on the Multi-Professional Patient Safety Curriculum Guide, published by the World Health Organization. we found that, of the 26 subjects in each course, the tracking terms were found in 22 subjects in the A/C courses, 23 in the B course. The topics of the guide with the highest number of terms were the improvement in medication safety, with 85 terms (22.6%), and Infection prevention and control, with 75 terms (20%). The contents do not express the comprehensiveness of patient safety education; some subjects had this focus, while others did not. the documents revealed gaps in the contents related to patient safety and demonstrated that they are addressed only in the course syllabus and discipline plans.


FIGHT-102: A phase 1 study of pemigatinib in Japanese patients with advanced malignancies.
FIGHT-102 was a phase 1, dose-escalation, dose-expansion study of pemigatinib in Japanese patients with advanced solid tumors. Here, we report safety, tolerability, and preliminary efficacy of pemigatinib from FIGHT-102. Patients (≥20 years old) self-administered oral pemigatinib 9, 13.5, or 18 mg QD on intermittent dosing (Part 1) or 13.5 mg QD intermittent or continuous dosing (Part 2). A dosing cycle was 21 days (2 weeks on/1 week off or 21 continuous days). Primary endpoint was safety. Secondary endpoints were pharmacokinetics, pharmacodynamics, and preliminary efficacy. Forty-four patients (Part 1, n = 14; Part 2, n = 30) were enrolled; most common tumors, cholangiocarcinoma, n = 8; esophageal, n = 6; 26 patients had confirmed FGF/FGFR alterations (Part 1, n = 3; Part 2, n = 23); 70.5% had ≥3 prior systemic therapies. Maximum tolerated dose was not identified. The recommended phase 2 dosage was determined to be 13.5 mg QD. Most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (81.8%), dysgeusia (45.5%), stomatitis (43.2%), and alopecia (38.6%); most frequent Grade ≥3 TEAEs were anemia and decreased appetite (9.1% each). In Part 1, no patient achieved partial response (PR) or complete response, and 7 (50.0%) patients had stable disease (SD). In Part 2, 5 (16.7%) patients achieved PR (one each with cholangiocarcinoma, gall bladder cancer, breast cancer, urothelial tract/bladder cancer, and sweat gland carcinoma) and 6 (20%) had SD. Median duration of response was 9.56 months (95% CI: 4.17, 14.95). Pemigatinib demonstrated manageable adverse events, consistent pharmacokinetics and pharmacodynamics profiles, and preliminary efficacy in Japanese patients with advanced solid tumors.


[Reflux esophagitis: a comparative study of lansoprazole and omeprazole as short-term therapy. Preliminary report].
Reflux Esophagitis is a common complaint from the upper gastrointestinal tract with a figured out prevalence of about 2%. Therapeutic results in this pathology have been unsatisfactory. To compare lansoprazole and omeprazole therapeutic effects in patients with reflux esophagitis. A clinical, double-blinded, balanced survey was randomly designed with patients who would daily receive 30 mg lansoprazole (Group A) or 20 mg omeprazole (Group B) during a 4-week period. All patients were submitted to endoscopy and biopsy both at the beginning and at the end of the survey. Ten patients in each group were treated without any significant differences in sex, age, nicotinism, alcoholism, AINES ingestion, development time, pain regurgitations, pyrrosis, hematemesis, dysphagia, melena, nausea or vomiting, and esophagitis degree. A complete cure in 8/10 (omeprazole) and 7/10 (lansoprazole) patients was obtained (p = n.s.). However, the histological results of the biopsy at the end of the four-week period proved to be a failure in 4/10 (omeprazole) and in 5/10 (lansoprazole) patients (p = n.s.). The endoscopy and clinical result at the end of the study were similarly effective; but not so the histological damage to the esophagus, which continues to be important. The use of bomb inhibitors in esophagitis by reflux is advisable. Future surveys must assess the average time of treatment for the disappearance of the histologic lesion.


Perception of peer advice in online health communities: Access to lay expertise.
When seeking advice online about health concerns, forums dedicated to medical themes are increasingly becoming an appreciated source of information for many individuals. In online health communities, patients can ask questions or otherwise seek advice that is particularly relevant to them. While they may find some of the advice useful, other advice may be perceived as less valuable. By studying the advice-seeking, advice-giving, and advice-evaluation behaviours in one of the largest online health communities in Europe, this paper looks at what determines which advice is perceived as helpful, and why. Drawing on network theory, we analysed the interaction data of 108,569 users over twelve consecutive years based on all publicly available information of an established Q&A online health community. Utilising zero-inflated negative binominal modelling, our results show that advice received from others, who have similar predominant interests, is valued more when reaching out for lay expertise. If this advice is given by peers, who can also draw on expertise from other health areas, allowing for a combination of diverse "lay" expertise, the advice is valued even more. Advice provided by those who are quick to obtain the latest knowledge available in the larger community further reinforces these effects. Our findings offer an original view to understand the influence of lay expertise exchanged via online health communities and hold implications for both policy-makers and medical practitioners regarding their approach to patient-initiated use of social media for health-related reasons.


Transformation and toxicity studies of UV filter diethylamino hydroxybenzoyl hexyl benzoate in the swimming pools.
Diethylamino hydroxybenzoyl hexyl benzoate (DHHB), an ultraviolet (UV) filter, can be found in sunscreens and other personal care products and thus can be introduced into swimming pools through the swimmers. In outdoor pools, DHHB will inevitably interact with free chlorine and sunlight. Therefore, the mechanism of solar‑chlorine chemical transformation of DHHB, as well as the environmental risk, were investigated in this work. In chlorinated with solar (Cl + solar) process, free chlorine was the dominant contributor to 85% of the DHHB degradation, while hydroxyl radicals and reactive chlorine species contributed only 15% because of low free radical generation and fast DHHB and free chlorine reaction rates. Scavenging matrices, such as Cl-, NH4+, and dissolved organic matter (DOM), inhibited the degradation of DHHB in the Cl + solar process, while Br-, HCO3-, NO3-, and urea promoted DHHB degradation. DHHB degradation was inhibited in tap water swimming pool samples, while it was enhanced in seawater pool samples by the Cl + solar process. Seven transformation by-products (TBPs) including mono-, dichlorinated, dealkylate, and monochloro-hydroxylated TBPs were identified. Three degradation pathways, chlorine substitution, chlorine and hydroxyl substitution, and dealkylation were proposed for DHHB transformation in the Cl + solar process. Both Quantitative structure-activity relationship and Aliivibrio fischeri toxicity tests demonstrated increased toxicity for the chlorinated TBPs. A risk assessment of the DHHB and its TBPs suggested that both DHHB and its chlorinated TBPs pose a significant health risk.


Diffusion kurtosis imaging combined with molecular markers as a comprehensive approach to predict overall survival in patients with gliomas.
The purpose of this study was to explore the usefulness of diffusion kurtosis imaging (DKI) and molecular markers in predicting the prognosis of glioma patients. Fifty-one patients with gliomas were examined by conventional MRI and DKI at 3.0 T before operation. The mean kurtosis (MK), mean diffusivity (MD), axial kurtosis (AK), and radial kurtosis (RK) values of tumors were measured and normalized to the contralateral normal-appearing white matter. The molecular markers of gliomas, including isocitrate dehydrogenase-1 (IDH1), α thalassemia/mental retardation syndrome x-linked (ATRX) and O6-methylguanine-DNA methyltransferase (MGMT), were immunohistochemically stained on the resected tumor tissues. Statistical methods, including the chi-square test, independent sample t-test, receiver operating characteristic curve analysis, Kaplan-Meier curve analysis, and Cox regression analysis were performed. The patients with lower MK, AK, RK, and higher MD values showed significantly better prognosis (P < 0.001). Survival time was better in glioma patients with IDH1 mutation (P < 0.01), ATRX loss of expression (P < 0.05), and MGMT negative expression (P < 0.05). However, among the groups of gliomas with IDH1 wild type, ATRX retention and those with MGMT positive expression, the patients with lower MK showed better outcome (P < 0.01). Cox multivariate regression analysis demonstrated that MK, RK values and ATRX retention could be used as independent prognostic risk factors, and high MK values had the highest risk for prognosis (HR = 65.288). Molecular markers and DKI parameters, especially MK values, can be used to effectively evaluate the prognosis of glioma patients.


A comparison of prostate health index, total PSA, %free PSA, and proPSA in a contemporary US population-The MiCheck-01 prospective trial.
Increasing numbers of patients are presenting with aggressive prostate cancer (CaP); therefore, there exists a need to optimally identify these patients pre-biopsy. To compare the accuracy of total prostate specific antigen (PSA), %free PSA, and prostate health index (PHI) to differentiate between patients without CaP, with non-aggressive (Gleason 3 + 3, non-AgCaP) and with aggressive (Gleason ≥ 3 + 4, AgCaP) in a contemporary US population. Serum samples were collected from 332 US patients scheduled for biopsy due to an elevated age-adjusted PSA. Site and Central biopsy pathologic assessment were performed. Testing of PSA, free PSA, proPSA, and PHI was performed along with central pathology review. Test performance using logistic regression analysis for differentiating CaP from non-CaP as well as non-AgCaP from AgCaP was evaluated. Central pathology review resulted in 32 upgrades including 14 Gleason 3 + 3 scores being upgraded to AgCaP with final distribution of 148 no-CaP, 64 non-AgCaP, and 120 AgCaP patients. Receiver operator curve (ROC) analysis of the different tests showed that PHI performed best at differentiating CaP from no-CaP subjects (area under the receiver operator curve 0.79). In contrast, the different tests were essentially equivalent in differentiating AgCaP vs. non-AgCaP. In this recent US study of prebiopsy patients we observed a high proportion of AgCaP patients consistent with previous studies in contemporary US populations. Central Gleason review is recommended for multi-institutional studies comparing biomarkers. PHI was superior to PSA, free PSA, %free PSA, and proPSA in detecting CaP in this population but was not superior at differentiating AgCaP from non-AgCaP.


Clinical relevance of miR-423-5p levels in chronic obstructive pulmonary disease patients.
This study aimed to examine changes in miRNAs expression profile of COPD patients. Thirty-six COPD patients as well as thirty-three healthy volunteers were recruited. Total RNAs were collected from the plasma of each participant. The differentially expressed miRNAs in COPD were screened from the GEO database. RT-qPCR was carried out to detect miRNA expression. In total, 9 out of 55 miRNAs were expressed differentially in COPD patients. Confirmed by RT-qPCR validation, 6 miRNAs increased while 3 miRNAs decreased. Further analysis of miR-423-5p, which has not been reported in COPD, showed that AUC for the diagnosis of COPD was 0.9651, and miR-423-5p levels was inversely correlated with the duration of smoking. The present study demonstrates that miR-423-5p is a potential marker for identifying COPD patients.


Risk of virus and non-virus related malignancies following immunosuppression in a cohort of liver transplant recipients. Italy, 1985-2014.
This cohort study assessed, in Italy, the overall pattern of risk of de novo malignancies following liver transplantation (LT). The study group included 2,832 individuals who underwent LT between 1985 and 2014 in nine centers all over Italy. Person-years (PYs) at cancer risk were computed from 30 days after LT to the date of cancer diagnosis, to the date of death or to the end of follow-up. Excess cancer risk, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). During 18,642 PYs, 246 LT recipients developed 266 de novo malignancies, corresponding to a 1.8-fold higher cancer risk (95% CI: 1.6-2.0). SIRs were particularly elevated for virus-related malignancies, including Kaposi's sarcoma (SIR = 53.6, 95% CI: 30.0-88.5), non-Hodgkin lymphomas (SIR = 7.1, 95% CI: 4.8-10.1) and cervix uteri (SIR = 5.4, 95% CI: 1.1-15.8). Among virus-unrelated malignancies, elevated risks emerged for head and neck (SIR = 4.4, 95% CI: 3.1-6.2), esophagus (SIR = 6.7, 95% CI: 2.9-13.3) and adrenal gland (SIR = 22.9, 95% CI: 2.8-82.7). Borderline statistically significant elevated risks were found for lung cancer (SIR = 1.4, 95% CI: 1.0-2.1) and skin melanoma (SIR = 2.6, 95% CI: 1.0-5.3). A reduced risk emerged for prostate cancer (SIR = 0.1, 95% CI: 0.0-0.5). These findings underline the need of preventive interventions and early detection of malignancies, specifically tailored to LT recipients.


The new era of quantitative cell imaging-challenges and opportunities.
Quantitative optical microscopy-an emerging, transformative approach to single-cell biology-has seen dramatic methodological advancements over the past few years. However, its impact has been hampered by challenges in the areas of data generation, management, and analysis. Here we outline these technical and cultural challenges and provide our perspective on the trajectory of this field, ushering in a new era of quantitative, data-driven microscopy. We also contrast it to the three decades of enormous advances in the field of genomics that have significantly enhanced the reproducibility and wider adoption of a plethora of genomic approaches.


Deafening-induced rapid changes to spine synaptic connectivity in the adult avian vocal basal ganglia.
The basal ganglia have been implicated in auditory-dependent vocal learning and plasticity in human and songbirds, but the underlying neural phenotype remains to be clarified. Here, using confocal imaging and three-dimensional electron microscopy, we investigated striatal structural plasticity in response to hearing loss in Area X, the avian vocal basal ganglia, in adult male zebra finch (Taeniopygia guttata). We observed a rapid elongation of dendritic spines, by approximately 13%, by day 3 after deafening, and a considerable increase in spine synapse density, by approximately 61%, by day 14 after deafening, compared with the controls with an intact cochlea. These findings reveal structural sensitivity of Area X to auditory deprivation and suggest that this striatal plasticity might contribute to deafening-induced changes to learned vocal behavior.


Physical Activity Behavior After a Diagnosis of Lung Cancer Differs Between Countries: An Observational Cohort Study.
Physical activity (PA) is important in lung cancer. To investigate PA levels and health-related quality of life (HRQoL) of patients with lung cancer in China and compare this to a similar cohort in Australia. Prospective cohort study. 71 patients from China (group CH) and 90 patients from Australia (group AU) with newly diagnosed lung cancer. Questionnaires assessed self-reported PA levels and HRQoL at baseline (diagnosis) and 8 weeks. At baseline, group CH were engaged in less overall PA than group AU (Physical Activity Scale for the Elderly [PASE] total score: median [IQR] group CH, 56 [32-59]; group AU, 66 [38-116]; P < .005), and less occupational and household activity ( P < .005). However, at baseline, group CH reported significantly more walking time than group AU (median [IQR]: group CH, 210 [150-315] min/wk; group AU, 55[0-210] min/wk; P < .0005). Global HRQoL scores were similar between groups (P = .038). Over 8 weeks, group CH increased their overall PA levels ( P < .005) and walking time ( P = .008), and HRQoL remained unchanged. The comparison group AU experienced a reduction in PA levels ( P = .02) and HRQoL ( P < .005). A diagnosis, patients in China were less physically active than those in Australia. Following diagnosis, patients in China increased their PA levels, whereas those in Australia reduced their PA levels. Research is required to explore potential reasons behind differences, and this may inform research/clinical services to facilitate patients with lung cancer to be more active.


A two-stage hybrid biomarker selection method based on ensemble filter and binary differential evolution incorporating binary African vultures optimization.
In the field of genomics and personalized medicine, it is a key issue to find biomarkers directly related to the diagnosis of specific diseases from high-throughput gene microarray data. Feature selection technology can discover biomarkers with disease classification information. We use support vector machines as classifiers and use the five-fold cross-validation average classification accuracy, recall, precision and F1 score as evaluation metrics to evaluate the identified biomarkers. Experimental results show classification accuracy above 0.93, recall above 0.92, precision above 0.91, and F1 score above 0.94 on eight microarray datasets. This paper proposes a two-stage hybrid biomarker selection method based on ensemble filter and binary differential evolution incorporating binary African vultures optimization (EF-BDBA), which can effectively reduce the dimension of microarray data and obtain optimal biomarkers. In the first stage, we propose an ensemble filter feature selection method. The method combines an improved fast correlation-based filter algorithm with Fisher score. obviously redundant and irrelevant features can be filtered out to initially reduce the dimensionality of the microarray data. In the second stage, the optimal feature subset is selected using an improved binary differential evolution incorporating an improved binary African vultures optimization algorithm. The African vultures optimization algorithm has excellent global optimization ability. It has not been systematically applied to feature selection problems, especially for gene microarray data. We combine it with a differential evolution algorithm to improve population diversity. Compared with traditional feature selection methods and advanced hybrid methods, the proposed method achieves higher classification accuracy and identifies excellent biomarkers while retaining fewer features. The experimental results demonstrate the effectiveness and advancement of our proposed algorithmic model.


Economic analysis of a phase III clinical trial evaluating the addition of total androgen suppression to radiation versus radiation alone for locally advanced prostate cancer (Radiation Therapy Oncology Group protocol 86-10).
To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer, using a Monte Carlo simulation of a Markov Model. Radiation Therapy Oncology Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT) alone or RT plus total androgen suppression (RTHormones) 2 months before and during RT for the treatment of locally advanced prostate cancer. A Markov model was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis took a payer's perspective. Transition probabilities from one state of health (i.e., with no disease progression or with hormone-responsive metastatic disease) to another were calculated from published rates pertaining to RTOG 86-10. Patients remained in one state of health for 1 year. Utility values for each health state and treatment were obtained from the literature. Distributions were sampled at random from the treatment utilities according to a second-order Monte Carlo simulation technique. The mean expected cost for the RT-only treatments was 29,240 dollars (range, 29,138-29,403 dollars). The mean effectiveness for the RT-only treatment was 5.48 quality-adjusted life years (QALYs) (range, 5.47-5.50). The mean expected cost for RTHormones was 31,286 dollars (range, 31,058-31,555 dollars). The mean effectiveness was 6.43 QALYs (range, 6.42-6.44). Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at 2,153 dollars/QALY. Cost-effectiveness acceptability curve analysis resulted in a >80% probability that RTHormones is cost-effective. Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range.


The impact of improved wood-burning stoves on fine particulate matter concentrations in rural Mexican homes.
To evaluate the impact of improved wood burning stoves on indoor air pollution, 53 homes in a rural town in Michoacán, Mexico, were selected from a health intervention study and monitored before and after receiving improved wood-burning stoves. Fine particulate matter--particles with aerodynamic diameter less than 2.5 microm (PM(2.5))--concentrations were measured in the central plaza of the community and in three microenvironments in the home (next to the stove, in the kitchen away from the stove, and outdoor patio). Forty-eight hour mean PM(2.5) concentrations in homes that burned wood in open fires were 693 microg/m(3) (95% CI: 246-1338) near the stove, 658 microg/m(3) (95% CI: 67-1448) in the kitchen away from the stove, and 94 microg/m(3) (95% CI: 36-236) on the patio. Mean ambient 24-h concentrations in the main plaza of the community were 59 microg/m(3) (95% CI: 29-92). Paired measurements before and after the installation of the Patsari improved wood-burning stove indicate a median 71% reduction in PM(2.5) concentrations near the stove and 58% reductions in kitchen concentrations, whereas patio and main plaza concentrations remain unaffected. Only 44% of participants reported to use their Patsari stoves exclusively during the transition period. Even with the predominant mixed use of the Patsari stove with open fires, estimated daily average personal exposures to PM(2.5) were reduced by 50%.


Degradation profile and identification of the major degradation products of dobupride under several conditions by GC/MS and HPLC-particle beam/MS.
The effect of pH, light, temperature and oxygen on the stability of dobupride (1), a novel gastroprokinetic drug, has been studied, storing the sample in the solid state and as a solution in methanol-water. The main forced degradation products have been identified by means of techniques such as GC/MS and HPLC-particle beam/MS, and two major degradation pathways have been characterized. One degradation route involves the loss of chlorine, yielding 4-amino-2-butoxy-N-[1-(1,3-dioxolan-2-ylmethyl)piperid -4-yl]benzamide (4) as the major degradation product. The second pathway results from cleavage of the piperidine-amide bond, producing 4-amino-2-butoxy-5-chlorobenzamide (2) as the major degradation product. Under the studied conditions, except when exposed to direct light in solution, dobupride has been shown to be very stable: after 5 months storage, the benzamide 2 (second pathway) was the only product identified (less than 0.5%). However, when dobupride in solution is exposed to natural or artificial sunlight, degradation is very fast, and after 7 days only 5% of the unchanged product remains. Under these circumstances, the main degradation route is the first one, with compound 4 being the most abundant degradation product, and compound 2 only being detectable in small amounts.


Pseudo 2:1 AV Block From Acquired Long QT Syndrome From Eating Clay.
Age-related degeneration of the cardiac conduction system is an important cause of heart block and a leading indication for permanent pacemaker implantations. However, variations in the myocardial refractory periods from QT interval prolongation or concealed atrioventricular node penetration from premature ventricular complexes can lead to unusual forms of conduction block not requiring permanent pacemaker implantation. (Level of Difficulty: Advanced.).


PI-RADS 2.1 - Image Interpretation: The Most Important Updates and Their Clinical Implications.
Multiparametric magnetic resonance imaging (MRI) of the prostate plays a central role in the diagnosis of patients with suspected prostate cancer. The increasing distribution and application of the guideline for the standardization of image acquisition, evaluation, and reporting (Prostate Imaging - Reporting and Data System, PI-RADS), which was updated in 2019 to version 2.1, contributes to the success of the technique. The most important updates of PI-RADS version 2.1 presented in 2019 compared to the previous version PI-RADS 2.0 are highlighted and interpreted with regard to their clinical implications. PI-RADS version 2.1 aims to simplify the application of the scoring scheme without changing the basic concept of dominant sequences (DWI in the peripheral zone, T2 in the transition zone). Of particular importance are the increasing role of diffusion-weighted imaging in the transition zone, the now mandatory high b-value of at least 1400 s/mm2, and new information on the assessment of the central zone and the anterior fibromuscular stroma. PI-RADS version 2.1 published in 2019 addresses a number of changes to the previous version, including both the examination technique and image interpretation. Prospective clinical studies have yet to prove the extent to which the goals of reducing interreader variability and increasing the detection rate in the transition zone will be achieved. · The new PI-RADS version 2.1. includes changes regarding image interpretation and examination technique. · The role of diffusion-weighted imaging is strengthened in the transition zone. · An ultra-high b-value of at least 1400 s/mm2 is mandatory according to PI-RADS 2.1. · Biparametric MRI is not recommended for general application. · Beyer T, Schlemmer H, Weber M et al. PI-RADS 2.1 - Image Interpretation: The Most Important Updates and Their Clinical Implications. Fortschr Röntgenstr 2021; 193: 787 - 795.


Prevalence of major and minor depression in elderly persons with mild cognitive impairment--MADRS factor analysis.
The aim of the study was to detect the prevalence of depressive syndromes and symptoms in the sample of elderly persons with Mild Cognitive Impairment (MCI), and to analyse Montgomery-Asberg Depression Rating (MADRS) item scores. The subjects of the study were 102 consecutive out-patients with MCI. All subjects were assessed by an experienced psychiatrist and MADRS was applied. Major and minor depressive episodes were defined according to DSM-IV criteria. Factor analysis was used to analyse baseline MADRS item scores. Three patient groups emerged according to the depressive symptoms distribution and severity scores basis: those with major depression constituted 19.6% (n = 20), with minor depression 26.5% (n = 27), and with very few depressive symptoms 53.9% (n = 55). Three interpretable MADRS factors were identified, using the factor analysis with Varimax rotation: the first consisting of apparent and reported sadness, inability to feel, pessimistic thoughts, the second consisting of inner tension, reduced sleep, reduced appetite, suicidal thoughts, and the third with concentration difficulties and lassitude. It was concluded that both major and minor depression is common in MCI. Three MADRS factors were identified and labelled as anhedonia-pessimism, anxiety-vegetative, and cognitive-inhibition.


Tai chi for management of type 2 diabetes mellitus: a systematic review.
Tai chi has been recommended for treating type 2 diabetes mellitus. The purpose of this systematic review was to evaluate evidence from controlled clinical trials testing the effectiveness of tai chi in treating type 2 diabetes mellitus. Systematic searches were conducted on 14 electronic databases without restrictions on either population characteristics or language of publication. The outcome measures considered for inclusion were changes in fasting blood glucose (FBG), glycosylated haemoglobin A1c (HbA1c) and quality of life (QOL). Eight randomised clinical trials (RCTs) and two controlled clinical trials (CCTs) met all inclusion criteria. Three RCTs from 1 trial compared the effects of tai chi with sham exercise and failed to show effectiveness of tai chi on FBG, HbA1c, or QOL. The other 3 RCTs tested the effects of tai chi compared with other types of exercise on FBG. The meta-analysis failed to show an FBG-lowering effect of tai chi [n=118, weighted mean difference (WMD): -0.14 mmol/L, 95% CI: -0.86 to 0.58, P=0.70]. Four studies (2 RCTs and 2 CCT) compared tai chi with no treatment or self-management programme and failed to report significant differences between the experimental and control groups except for QOL from 1 RCT and 1 CCT. The existing evidence does not suggest that tai chi is an effective therapy for type 2 diabetes. Currently, there are few high-quality trials on which to make definitive judgements.


Safety and initial clinical efficacy of three dose levels of recombinant activated factor VII (rFVIIa): results of a phase I study.
The safety and efficacy of recombinant DNA-produced factor VIIa (rFVIIa) was investigated in 15 haemophilic patients in non-bleeding states and during bleeding episodes (mild to moderate joint bleed). Patients with severe haemophilia A without inhibitors (n = 4), haemophilia A with inhibitors (n = 10), and haemophilia B with inhibitor (n = 1) received one or more doses of rFVIIa during 32 non-bleeding study episodes and 23 bleeding episodes. The study was an open, uncontrolled, dose-escalation (17.5 micrograms/kg, 35 micrograms/kg, 70 micrograms/kg) trial. Physical evaluation, laboratory assessment, and immunology testing were conducted at baseline, monthly for 3 months and every 3 months thereafter. The immediate safety of rFVIIa was assessed by monitoring of D-dimer, fibrinogen, platelet count, antithrombin III, thrombin-antithrombin complex, and alpha 2-antiplasmin 5 min before and at multiple times throughout the following 24 h. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) values were also obtained. Pain, swelling, joint circumference, and range of motion were recorded before administration of the initial dose of rFVIIa in bleeding patients and at 6, 12, and 24 h. Haemostatic response to rFVIIa was observed in patients with severe VIII and IX deficiency with and without inhibitors. Therapy with rFVIIa was judged effective in 19 of the 22 evaluable bleeding episodes at one or more time points. The 35 micrograms/kg and 70 micrograms/kg doses were associated with higher response rates at 6 and 12 h compared to the 17.5 micrograms/kg dose level. A second dose of rFVIIa was administered in 20 of the 22 bleeding episodes.(ABSTRACT TRUNCATED AT 250 WORDS)


Dexamethasone suppresses the proliferation and migration of VSMCs by FAK in high glucose conditions.
High glucose conditions cause some changes in the vessels of diabetes through the signal transduction pathways. Dexamethasone and other corticosteroids have a wide range of biological effects in immunological events. In the present study, the effects of dexamethasone were investigated on the VSMC (vascular smooth muscle cell) proliferation, and migration based on the FAK gene and protein changes in high glucose conditions. The vascular smooth muscle cells were cultured in DMEM and were treated with dexamethasone (10-7 M, 10-6 M, and 10-5 M) for 24, and 48 h in high glucose conditions. The cell viability was estimated by MTT method. The FAK gene expression levels and pFAK protein values were determined by RT-qPCR and western blotting techniques, respectively. A scratch assay was used to evaluate cellular migration. The FAK gene expression levels decreased significantly dependent on dexamethasone doses at 24 and 48 h. The pFAK protein values decreased significantly with a time lag at 24- and 48-h periods as compared with gene expression levels. The results showed that the inhibition of VSMC proliferation and migration by dexamethasone in the high glucose conditions may be related to the changes of FAK.


Uterine viability in the baboon after ligation of uterine vasculature: a pilot study to assess alternative perfusion and venous return for uterine transplantation.
To assess, in two separate groups of baboons, uterine viability after ligation of the uterine veins and uterine viability after ligation of both the uterine arteries and veins, respectively. Prospective, observational study. Baboon breeding colony. Six naïve female Papio hamadryas baboons with indicators of normal reproductive function. Three baboons underwent surgical interruption of the uterine veins bilaterally, and three baboons underwent surgical interruption of the uterine arteries and the uterine veins bilaterally. All baboons also underwent colpotomy, cervico-vaginal reanastomosis, and intraoperative near-infrared fluorescence imaging after vessel ligation. In the postoperative period, transabdominal sonography, vaginoscopy, and endocervical biopsy were performed on all animals. Postoperative uterine and ovarian viability. Near-infrared imaging confirmed intraoperative perfusion of the uterus and cervico-vaginal anastomosis in all cases. In all subjects, sonography revealed normal uteri, and vaginoscopy revealed well-healed anastomoses. Endocervical biopsies (five of six) demonstrated pathologically normal endocervical tissue without evidence of necrosis. Cyclical sex skin turgescence and menstruation were unanimously observed. Disruption of bilateral uterine vessels does not affect uterine or ovarian viability in the baboon. Bilateral uterine artery and vein ligation furthers development of a minimally invasive approach to donor hysterectomy.


[Impact of the 2009 influenza A (H1N1) virus pandemic on the emergency department of a tertiary hospital].
The 2009 H1N1 influenza A virus infection pandemic was an important challenge for public health systems worldwide. A prospective study including all patients with an influenza-like illness, with microbiological criteria for 2009 H1N1 virus, from July to December 2009 seen in the paediatric emergency department. Viral testing was performed using multiplex real-time reverse transcription polymerase chain reaction (RT-PCR). We analysed the number of visits to, and hospital admissions from, our emergency department. We compared patients with laboratory-confirmed 2009 H1N1 virus with non-confirmed ones. A total of 1144 patients with microbiological criteria were identified. Of these, 513 (44.8%) were admitted to hospital, 12 of them (1%) to the PICU and 3 (0.3%) died. The majority of the patients (824; 72%) had some underlying medical condition. Of the 1144 patients, 412 (36%) had RT-PCR confirmed 2009 H1N1 infection, and 732 (64%) were not confirmed. The mean age of patients with 2009 H1N1 infection was higher than those not infected (median age: 7.4 vs 4.1 years; p<.001). Laboratory-confirmed 2009 pandemic H1N1 influenza patients had more underlying high-risk conditions (OR: 2.21 [1.65-2.96]), suffered from pneumonia in less cases (OR: 0.33 [0.23-0.49]) and were admitted to hospital in less cases (OR: 0.19 [0.14-0.24]). In our emergency department, we identified an important increase in the number of visits (12%) and admissions (5.7%) compared to the previous year, 2008. The 2009 pandemic H1N1 influenza caused significant morbidity but the mortality was not significant. The majority of children with laboratory-confirmed 2009 H1N1 virus had uncomplicated illnesses despite the increased presence of high-risk conditions.


Gynecologic Malignancies in Pregnancy: Balancing Fetal Risks With Oncologic Safety.
Cancer occurs in 0.05% to 0.1% of all pregnancies. Despite literature reporting good oncologic and fetal outcomes in women treated for cancer during pregnancy, as many as 44% of gynecologists would offer termination, and 37% would not administer chemotherapy or radiotherapy in pregnancy. The aims of this study were to summarize current recommendations for the treatment of cervical and ovarian cancers in pregnancy and to review updates on existing knowledge regarding the safety of surgical and chemotherapeutic treatments in pregnancy, including both oncologic and fetal outcomes. A detailed literature review was performed on PubMed. The treatment of gynecologic malignancies during pregnancy mirrors that outside pregnancy, with a balance between maternal versus fetal health. Fertility-sparing surgery can be offered to stage IA2 and low-risk IB1 cervical, stage I epithelial ovarian, germ cell ovarian, or sex-cord stromal ovarian tumors. Delayed treatment can be offered for stage IB1 cervical cancer. Neoadjuvant and/or adjuvant chemotherapy can be given for advanced gynecologic cancers with good disease-free survival without significant adverse neonatal outcomes. A multidisciplinary approach and improved education of providers regarding the surgical and chemotherapeutic treatments in pregnancy are needed in order to fully inform patients regarding treatment options. Further research in women who are pregnant is needed to determine the safety of diagnostic and therapeutic procedures used in the nonpregnant woman. This article reviews and supports treatment of gynecologic cancer during pregnancy, calls for additional study and long-term follow-up, and justifies improved education of patients and providers regarding treatment options. Obstetricians and gynecologists, family physicians. After completing this activity, the learner should be better able to (1) review general principles in the management and treatment of gynecologic cancers in pregnancy, (2) review the diagnosis and treatment of cervical cancer in pregnancy, and (3) review the diagnosis and treatment of ovarian cancer in pregnancy.


Influence of psychological response on breast cancer survival: 10-year follow-up of a population-based cohort.
The possibility that psychological response within a few weeks of a breast cancer diagnosis can influence the outcome of the disease is a contentious issue. Psychological response, including helplessness/hopelessness, fighting spirit and depression was assessed in early-stage breast cancer patients between 1 and 3 months post-diagnosis, in order to ascertain effect on cancer prognosis. Patients were followed up for a period of 10 years in order to clarify the effect of psychological response on disease outcome. After 10 years, there is a continuing effect of helplessness/hopelessness on disease-free survival (adjusted hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.11-2.11) but not of depression (adjusted HR for overall survival for 'cases' 2.43, 95% CI 0.97-6.10). Longer follow-up also indicates that a high fighting spirit confers no survival advantage. The results showed that, in patients who were disease-free at 5 years, their baseline helpless/hopeless response still exerted a significant effect on disease-free survival beyond 5 (and up to 10) years. The effect is therefore maintained for up to 10 years of follow-up. Clinicians may wish to screen for helplessness around the time of diagnosis in order to target psychological care resources. Further large studies, with similarly prolonged follow-up, are needed to replicate this effect and clarify its mechanism of action.


Impact of multiple prenatal risk factors on newborn iron status at delivery.
Maternal anemia and several complications of pregnancy can affect fetal iron acquisition. Because it is unknown whether the effects of demographic and maternal risk factors (RF) are summative, we examined cord iron status in newborns with multiple RF for acquiring iron deficiency. Cord blood indices from healthy control newborns with and without RF for newborn or infant iron deficiency were studied. Newborns with greater RF had poorer erythrocyte and storage iron status. Poorest status was seen if mothers with comorbid obesity and diabetes delivered large-for-gestation newborns. Findings highlight the importance of identifying RF.


H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity.
Epigenetic mechanisms contribute to the regulation of cell differentiation and function. Vascular smooth muscle cells (SMCs) are specialized contractile cells that retain phenotypic plasticity even after differentiation. Here, by performing selective demethylation of histone H3 lysine 4 di-methylation (H3K4me2) at SMC-specific genes, we uncovered that H3K4me2 governs SMC lineage identity. Removal of H3K4me2 via selective editing in cultured vascular SMCs and in murine arterial vasculature led to loss of differentiation and reduced contractility due to impaired recruitment of the DNA methylcytosine dioxygenase TET2. H3K4me2 editing altered SMC adaptative capacities during vascular remodeling due to loss of miR-145 expression. Finally, H3K4me2 editing induced a profound alteration of SMC lineage identity by redistributing H3K4me2 toward genes associated with stemness and developmental programs, thus exacerbating plasticity. Our studies identify the H3K4me2-TET2-miR145 axis as a central epigenetic memory mechanism controlling cell identity and function, whose alteration could contribute to various pathophysiological processes.


The chemokine system in experimental and clinical hematology.
The chemokine family consists of approximately 50 small (8-14 kDa), basic proteins that are expressed and released by a wide range of normal and malignant cells. Based on their molecular structure, these cytokines are divided into the two major subgroups CCL and CXCL chemokines that bind to CCR or CXCR receptors, respectively. These mediators are important for regulation of cell viability, proliferation, differentiation, and migration. Chemokines are important for cell migration during embryogenesis; they are involved in the regulation of complex processes like local recruitment of inflammatory cells, angiogenesis, and regulation of normal as well as leukemic hematopoiesis. Chemokines can be constitutively released by malignant hematopoietic cells as well as by bone marrow stromal cells. This bidirectional crosstalk between malignant hematopoietic cells and neighboring stromal cells may therefore be important for the development and clinical presentation of malignant diseases, and the chemokines or their receptors may also represent a target for specific anticancer therapy at the molecular level.


Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies.
The impact of anti-HLA antibodies, except for donor-specific anti-HLA-A, -B, -DRB1 antibodies, on engraftment was retrospectively evaluated in 175 single cord blood transplantations (CBT). Patients and donors had been typed at HLA-A, -B, and -DRB1 antigens, and anti-HLA antibodies had been screened before transplantation to avoid the use of cord blood (CB) units with corresponding antigens. The median age was 59 (range, 17 to 74) years. Overall, 61% were male, 89% had high-risk disease status, 77% received myeloablative conditioning regimens, and over 80% were heavily transfused patients. Sixty-nine of the 175 (39.4%) were positive for anti-HLA antibodies. Thirty-nine patients had antibodies only against HLA-A, -B, or -DRB1, 13 had antibodies only against HLA-C, -DP, -DQ, or -DRB3/4/5, and 17 had antibodies both against HLA-C, -DP, -DQ, or -DRB3/4/5 and against HLA-A, -B, or -DRB1. Because CB units had not been typed at HLA-C, -DP, -DQ, or -DRB3/4/5, it was possible that antibodies against them were unrecognized donor-specific antibodies. Patients with antibodies only against HLA-A, -B, or -DRB1 showed comparable neutrophil engraftment rates to those without antibodies (89.7% versus 83%, P = .65), whereas patients having antibodies against C, DP, DQ, or -DRB3/4/5 showed lower engraftment rate (66.7%, P = .12), which became statistically significant in a subgroup of HLA-mismatched donor-recipient pairs (50%, P = .01). Our results demonstrated that the presence of donor nonspecific anti-HLA-A, -B, -DRB1 antibodies had no significant influence on engraftment, whereas anti-HLA-C, -DP, -DQ, or -DRB3/4/5 antibodies adversely affect engraftment, possibly because of unrecognized donor-specific anti-HLA antibodies against them, especially in HLA-mismatched CBT.