Molecular implications of Ph (+) myelodysplastic syndrome.
We report a case of 62-year-old Japanese male with a myelodysplastic syndrome (MDS) with a Philadelphia (Ph) chromosome. Cytogenetic analysis revealed the bone marrow cells to contain a Ph chromosome due to t(?;11;22) (?;q11;q11), as well as -5, -7, +8, -12 and an extra Ph, in addition to cells with a normal karyotype. Molecular analysis using breakpoint cluster region probes (5' bcr and 3' bcr) did not detect a rearrangement within the bcr DNA sequences, indicating that the breakpoint at 22q11 occurred outside the bcr. Furthermore, the bone marrow cells from this patient did not express an 8.5 kb c-abl mRNA. Thus, the Ph translocation in this case differs from that of Ph-positive chronic myelogenous leukemia.


Applications of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) in pharmaceutical and biological analysis.
Conductivity detection, which is universal in capillary electrophoresis (CE), has received considerable attention, since the introduction of the axial capacitively coupled contactless detector C(4)D in 1998. This detector is made of two electrodes which are placed cylindrically around the CE capillary and connected to the AC oscillator. The distance between the electrodes is the detection gap. In this review, applications of CE and MCE with C(4)D in pharmaceutical and biological analysis are presented.


Effect of dieldrin and calcium on the performance of adult Japanese quail (Coturnix coturnix japonica).
Two experiments were conducted to determine the effects of dieldrin and calcium on reproductive performance of quail. At 25% egg production the quail received diets containing 0,10 or 25 p.p.m. of dieldrin for 6, 28-day periods in experiment 1 and 0, 5, or 25 p.p.m. of dieldrin for 4, 28-day periods in experiment 2. Pesticide treatments were employed with diets containing 0.5% and 3.0% calcium. The results show that egg shell thickness, cracked eggs, egg production, feed consumption, egg weights, fertility, hatchability and body weights were not affected by dieldrin treatments. However, egg shell thickness, cracked eggs, egg production and hatchability were adversely affected by the lower calcium level. Female body weights were consistently heavier for the low calcium diet. Mortality increased in the presence of 10 and especially 25 p.p.m. of dieldrin. Livability of chicks from hens receiving rations with 10 and 25 p.p.m. of dieldrin was significantly lower than those fed no dieldrin. In summary, dieldrin was without effect on egg shell quality or other reproductive factors but did exert a detrimental effect on adult mortality and livability of progeny.


Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses.
Modern vaccinology has increasingly focused on non-living vaccines, which are more stable than live-attenuated vaccines but often show limited immunogenicity. Immunostimulatory substances, known as adjuvants, are traditionally used to increase the magnitude of protective adaptive immunity in response to a pathogen-associated antigen. Recently developed adjuvants often include substances that stimulate pattern recognition receptors (PRRs), essential components of innate immunity required for the activation of antigen-presenting cells (APCs), which serve as a bridge between innate and adaptive immunity. Nearly all PRRs are potential targets for adjuvants. Given the recent success of toll-like receptor (TLR) agonists in vaccine development, molecules with similar, but additional, immunostimulatory activity, such as defective interfering particles (DIPs) of viruses, represent attractive candidates for vaccine adjuvants. This review outlines some of the recent advances in vaccine development related to the use of TLR agonists, summarizes the current knowledge regarding DIP immunogenicity, and discusses the potential applications of DIPs in vaccine adjuvantation.


Facial nerve paralysis. 1. General evaluation, Bell's palsy.
The correct diagnosis of facial paralysis is not easily made but is important for proper management, since such paralysis is a sign or symptom of an underlying disorder. The clinician must be able to make an accurate and complete assessment of the entire facial nerve. Once a diagnosis is made, information from the history and results of topographic and electrical testing can be used in planning management and treatment. Bell's palsy, which is idiopathic, is the most common cause of facial paralysis. It is acute in onset and can come from a variety of causes. In the large majority of patients, the condition resolves either spontaneously or with treatment. Currently available treatments include corticosteroid therapy and facial nerve decompression, although both remain controversial.


Mycoplasma hominis Infections Transmitted Through Amniotic Tissue Product.
Mycoplasma hominis is a commensal genitourinary tract organism that can cause infections outside the genitourinary tract. We investigated a cluster of M. hominis surgical site infections in patients who underwent spine surgery, all associated with amniotic tissue linked to a common donor. Laboratory tests of tissue product from the donor, including culture, quantitative real-time polymerase chain reaction (qPCR), and whole-genome sequencing were performed. Use of this amniotic tissue product was reviewed. A multistate investigation to identify additional cases and locate any unused products was conducted. Twenty-seven tissue product vials from a donor were distributed to facilities in 7 states; at least 20 vials from this donor were used in 14 patients. Of these, 4 of 14 (29%) developed surgical site infections, including 2 M. hominis infections. Mycoplasma hominis was detected by culture and qPCR in 2 unused vials from the donor. Sequencing indicated >99% similarity between patient and unopened vial isolates. For 5 of 27 (19%) vials, the final disposition could not be confirmed. Mycoplasma hominis was transmitted through amniotic tissue from a single donor to 2 recipients. Current routine donor screening and product testing does not detect all potential pathogens. Clinicians should be aware that M. hominis can cause surgical site infections, and may not be detected by routine clinical cultures. The lack of a standardized system to track tissue products in healthcare facilities limits the ability of public health agencies to respond to outbreaks and investigate other adverse events associated with these products.


Impacts of Stress Response and Negative Emotion on Mental Health of College Students During the COVID-19 Outbreak.
In this study, we aimed to explore the influences of stress responses and negative emotion on mental health of college students during the initial COVID-19 outbreak in China. A nationally representative sample of 1,351 college students, aged 18-23 years, took part in an online survey during the COVID-19 outbreak. The ANOVA, correlation coefficients, structural equation modeling (path analysis), and other statistical analysis methods were used for data analysis. (1) The Chinese college students' epidemic panic and cognitive evaluation were found to be moderate (3.73 ± 0.74, 3.76 ± 0.62), while their defensive response was higher (4.61 ± 0.55). Their mental health during the COVID-19 outbreak was found to be good (3.75 ± 0.76). (2) The quality of their mental health was significantly and negatively associated with epidemic panic, and the quality of their mental health was significantly and positively associated with defensive response. (3) The quality of their mental health was significantly and negatively associated with negative emotion. (4) College students' epidemic panic and defensive response to the COVID-19 had a directly predictive effect on their mental health. College students' negative emotion played a partial mediating role in the relationship between epidemic panic and mental health. College students' negative emotion played a complete mediating role in the relationship between cognitive appraisal and mental health.


Detection of tACS Entrainment Critically Depends on Epoch Length.
Neural entrainment is the phase synchronization of a population of neurons to an external rhythmic stimulus such as applied in the context of transcranial alternating current stimulation (tACS). tACS can cause profound effects on human behavior. However, there remain a significant number of studies that find no behavioral effect when tACS is applied to human subjects. To investigate this discrepancy, we applied time sensitive phase lock value (PLV) based analysis to single unit data from the rat motor cortex. The analysis revealed that detection of neural entrainment depends critically on the epoch length within which spiking information is accumulated. Increasing the epoch length allowed for detection of progressively weaker levels of neural entrainment. Based on this single unit analysis, we hypothesized that tACS effects on human behavior would be more easily detected in a behavior paradigm which utilizes longer epoch lengths. We tested this by using tACS to entrain tremor in patients and healthy volunteers. When the behavioral data were analyzed using short duration epochs tremor entrainment effects were not detectable. However, as the epoch length was progressively increased, weak tremor entrainment became detectable. These results suggest that tACS behavioral paradigms that rely on the accumulation of information over long epoch lengths will tend to be successful at detecting behavior effects. However, tACS paradigms that rely on short epoch lengths are less likely to detect effects.


Choroidal thickness, myopia, and myopia control interventions in children: a Meta-analysis and systemic review.
To investigate changes of choroidal thickness (ChT) in children with myopia and the effect of current myopia control interventions on ChT. Major literature databases were searched for studies relevant to myopia in children. All studies used swept-source optical coherence tomography (SS-OCT) or enhanced depth imaging optical coherence tomography (EDI-OCT) to measure the ChT value. The weighted mean difference (WMD) and 95% confidence interval (CI) were pooled to evaluate ChT in myopia children. A total of 11 eligible articles, including 1693 myopic and 1132 non-myopic eyes, were included in the first Meta-analysis. The sub-foveal choroidal thickness (SFCT; WMD=-40.06, 95%CI, -59.36 to -20.75, P<0.001) and ChT at other sectors were significantly thinner in myopic eyes compared with the non-myopic eyes. The Meta-analysis revealed that the ChT decreased horizontally from the temporal sector toward the nasal sector in the pediatric myopia population. Another 11 studies reporting the effect of myopia control interventions were included in the second Meta-analysis for the relationship between myopia control treatments and ChT. SFCT significantly increased after orthokeratology (OK) treatment and OK combined with 0.01% atropine (OKA) treatment (WMD=19.47, 95%CI, 15.96 to 22.98, P<0.001; WMD=21.81, 95%CI, 12.92 to 29.70, P<0.001, respectively). The forest plots showed that SFCT changed little in myopic children receiving 0.01% atropine (P=0.30). Furthermore, the Meta-analysis showed that OK treatment had a stronger effect on the value of SFCT in myopic children as compared with 0.01% atropine (WMD=9.86; 95%CI, -0.21 to 19.93, P=0.05). There is no difference between the treatment with OK and OKA treatment in ChT in myopic children (P=0.37). The ChT in myopic eyes is thinner than that in non-myopic eyes in pediatric population. Myopia control interventions including OK and OKA lead to ChT thickening, but other treatments such as 0.01% atropine did not show an increase in ChT.


Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia.
Vancomycin-resistant Enterococcus faecium bloodstream infections (VREF-BSI) cause significant mortality, highlighting the need to optimize their treatment. We compared the effectiveness and safety of daptomycin (DAP) and linezolid (LZD) as continuous or sequential therapy for VREF-BSI in a national, retrospective, propensity score (PS)-matched cohort study of hospitalized Veterans Affairs patients (2004 to 2014). We compared clinical outcomes and adverse events among patients treated with continuous LZD, continuous DAP, or sequential LZD followed by DAP (LZD-to-DAP). Secondarily, we analyzed the impact of infectious diseases (ID) consultation and source of VREF-BSI. A total of 2,630 patients were included in the effectiveness analysis (LZD [n = 1,348], DAP [n = 1,055], LZD-to-DAP [n = 227]). LZD was associated with increased 30-day mortality versus DAP (risk ratio [RR], 1.11; 95% confidence interval [CI], 1.01 to 1.22; P = 0.042). After PS matching, this relationship persisted (RR, 1.13; 95% CI, 1.02 to 1.26; P = 0.015). LZD-to-DAP switchers had lower mortality than those remaining on LZD (RR, 1.29; 95% CI, 1.03 to 1.63; P = 0.021), suggesting a benefit may still be derived with sequential therapy. LZD-treated patients experienced more adverse events, including a ≥50% reduction in platelets (RR, 1.07; 95% CI, 1.03 to 1.11; P = 0.001). DAP was associated with lower mortality than was LZD in patients with endocarditis (RR, 1.20; 95% CI, 1.02 to 1.41; P = 0.024); however, there was no statistically significant association between treatment group and mortality with regard to other sources of infection. Therefore, source of infection appears to be important in selection of patients most likely to benefit from DAP over LZD.


Nuchal cord and perinatal outcome.
to find out the incidence of nuchal cord at delivery, intrapartum complication and perinatal outcomes in the cases with nuchal cord. A prospective, cross-sectional, comparative study done at Kathmandu Medical College Teaching Hospital (KMCTH) between March 2006 to September 2006. Total 512 deliveries occurred during this period that were enrolled in the study and were analyzed for presence of nuchal cord at the time of delivery, number of coils whether loose or tight, intrapartum complications and perinatal outcome. The cases with nuchal cord at the time of delivery were taken as study group and the cases without nuchal cord served as control group. Outcome variables between the two groups were compared. Outcome variables used were meconium staining of liquor, rate of instrumental and caesarean delivery, intrapartum fetal heart rate (FHR) irregularities. As a measure of perinatal outcome Apgar score<7 at 1 minute and 5 minutes and incidence of neonatal unit admission was taken. Incidence of nuchal cord at the time of delivery was 22.85%. Incidence of single nuchal cord was highest (18.95%). Intrapartum complications like FHR irregularities and meconium staining of liquor were increased in nuchal cord group but statistically not significant. Instrumental delivery rate was high in nuchal cord group but statistically not significant (0.108). However, caesarean section rate was high in the group without nuchal cord (p=0.029). Apgar score<7 at 1 minute was significantly low in nuchal cord group (p=0.010) but apgar score at 5 minutes and admission to neonatal unit was not more common. Nuchal cord is not associated with adverse perinatal outcome.


[The mutation spectrum of phenylalanine hydroxylase gene in patients with phenylketonuria in Henan province].
To investigate the characteristics of the phenylalanine hydroxylase (PAH) gene mutations in patients with phenylketonuria (PKU) in Henan province, China, in order for providing basic information for clinical genetic counseling and prenatal diagnosis. All the exons and partial flanking introns of the PAH gene were detected by polymerase chain reaction (PCR) and bi-directional sequencing in 34 patients with PKU from Henan province. A total of 23 different disease-causing mutations were identified which corresponded to 92.65% (63/68) of the PAH alleles, including 12 missense mutations, 4 nonsense mutations, 4 splicing junction mutations, and 3 deletion mutations. Among them, A156P and P69_S70delinsP(delCTT) were novel mutations; IVS2+ 5G to C, G332E, IVS10-14C to G and L367 to Wfs were reported in Chinese population for the first time according to the PAH database (www.pahdb.mcgill.ca). Among all the 13 exons, exon 7 harbored the most type of mutations, exon 11 and exon 5 the second. The most common mutations included R243Q (17.65%, 12/68), V399V (11.76%, 8/68), IVS4-1G to A (8.82%, 6/68), R400T(7.35%, 5/68), Y166X(5.88%,4/68) and G247R(5.88%, 4/68). In addition, 9 other gene variations were found in this study. The mutation spectrum and frequency of the PAH gene of patients with phenylketonuria in Henan province were slightly different from those from other parts of China.


"Real" early orthodontic treatment. From birth to age 8.
This article will introduce new concepts for earlier orthodontic (teeth) and orthopedic (jaw-bone) diagnosis and treatment from birth to age eight. While early orthodontic treatment around age 8 is getting some attention, age 8 is still too late to orthopedically guide proper jaw and airway growth in some children. By age 8, the jaws (maxilla and mandible) grow 80-90% of their adult size. Research shows that small jaws create small airways and increase the likelihood of life-threatening disorders, for life. Since the upper and lower jaw-bones form the gateway to the human airway, a new earlier orthodontic protocol and standard is warranted. Unique Functional Jaw Orthopedic concepts will help form a new early orthodontic protocol. These new concepts may very well help general dentists, pedodontists and orthodontists move dental care into a future world of medical dentistry which will include airway development, bed-wetting, ear disease, heart disease and longevity.


Isolation of a family of Drosophila POU domain genes expressed in early development.
The POU domain is a approximately 140 amino acid domain shared by several mammalian transcriptional activators. We have isolated genomic and cDNA clones from three Drosophila POU domain genes, designated pdm-1, pdm-2, and Cf1a. All three genes encode a conserved POU-specific domain and a POU homeo domain but are otherwise divergent. By Northern analysis, all three of the genes are expressed in early embryos; the pdm-1 and Cf1a genes are also expressed at lower levels throughout development. The spatial expression patterns of the pdm-2 and Cf1a genes show that they probably play multiple roles during development: an early role in specific ectodermal cells, and a subsequent role in the embryonic nervous system.


Metformin synergistic pemetrexed suppresses non-small-cell lung cancer cell proliferation and invasion in vitro.
The aim of this study was to investigate whether metformin in combination with pemetrexed has an effect on the treatment of non-small-cell lung cancer (NSCLC) models and to explore the related molecular mechanism. The half maximal inhibitory concentration (IC50) and combination index (CI) of metformin and pemetrexed were detected by the CCK8 assay to assess the antiproliferative and therapeutic effects of the two-drug combination. Flow cytometry (FCM) and invasion assays were used to estimate the variation in apoptosis rate and invasion ability of the differently treated NSCLC cell lines. Apoptotic markers were detected by western blotting to validate the data related to the antiproliferation and proapoptosis effects. Metformin monotherapy inhibited the growth of NSCLC cell lines and reduced the invasion ability to different degrees compared with the control groups (P < 0.05). Metformin in combination with pemetrexed produced a synergistic effect (CI < 0.90) compared with the two drugs in monotherapy in the three tested NSCLC cell lines. Metformin in combination with pemetrexed significantly increased the cell numbers of HCC827 cells at S phase (P < 0.001), and the combination therapy had no influence on the A549 and H1975 cell lines. We found that combining metformin with pemetrexed induced more cell apoptosis than metformin or pemetrexed used alone (P < 0.05), which was validated by the apoptotic markers. These results demonstrate that the combination of metformin and pemetrexed has a synergistic effect on the treatment of NSCLC cell lines by inducing apoptosis or blocking the cell cycle. Our data indicate that the combination of metformin and pemetrexed could have beneficial antitumor effects on NSCLC cells in vitro.


[Primary intracranial malignant melanoma associated with nevus of Ota: a case report].
A case of intracranial malignant melanoma associated with nevus of Ota is presented. A 77-year-old man was admitted to the department of neurosurgery, Fukui Medical School on June, 1985 because of developing disturbed consciousness. The physical examination on admission revealed pigmented lesion diagnostic of the nevus of Ota, anisocoria (R greater than L) and left hemiparesis. Computed tomographic (CT) scans demonstrated a high density mass in the left temporal lobe and the mass was homogenously enhanced after the injection of contrast agent. Left common carotid angiogram showed elevation of the middle cerebral artery and a slight vascular blush. Subtotal removal of the dark-colored tumor within the left temporal lobe and biopsy of the nevus were performed. Histopathological examination of the tumor revealed malignant melanoma and that of the skin biopsy was consistent with a nevus of Ota. Postoperatively DTIC, ACNU and vincristine were administered intravenously but the patient died three weeks after operation. At autopsy, widespread black pigmentation of the leptomeninges, communicating with the pigmented tumor in the left temporal lobe, covered the base of the brain and spinal cord. No melanoma was found outside the central nervous system. Primary intracranial melanoma associated with nevus of Ota is rare and only 6 cases have been reported in the literature. In this paper, primary intracranial melanoma associated with nevus of Ota and some other subjects are discussed.


Microbiome Associated with Severe Caries in Canadian First Nations Children.
Young Indigenous children in North America suffer from a higher degree of severe early childhood caries (S-ECC) than the general population, leading to speculation that the etiology and characteristics of the disease may be distinct in this population. To address this knowledge gap, we conducted the first microbiome analysis of an Indigenous population using modern molecular techniques. We investigated the caries-associated microbiome among Canadian First Nations children with S-ECC. Thirty First Nations children <72 mo of age with S-ECC and 20 caries-free children were recruited in Winnipeg, Canada. Parents or caregivers completed a questionnaire on general and dental health, diet, and demographics. The plaque microbiome was investigated by sequencing the 16S rRNA gene. Sequences were clustered into operational taxonomic units and taxonomy assigned via the Human Oral Microbiome Database, then analyzed at the community level with alpha and beta diversity measures. Compared with those who were caries free, children with S-ECC came from households with lower income; they were more likely to live in First Nations communities and were more likely to be bottle-fed; and they were weaned from the bottle at a later age. The microbial communities of the S-ECC and caries-free groups did not differ in terms of species richness or phylogenetic diversity. Beta diversity analysis showed that the samples significantly clustered into groups based on caries status. Twenty-eight species-level operational taxonomic units were significantly different between the groups, including Veillonella HOT 780 and Porphyromonas HOT 284, which were 4.6- and 9-fold higher, respectively, in the S-ECC group, and Streptococcus gordonii and Streptococcus sanguinis, which were 5- and 2-fold higher, respectively, in the caries-free group. Extremely high levels of Streptococcus mutans were detected in the S-ECC group. Overall, First Nations children with S-ECC have a significantly different plaque microbiome than their caries-free counterparts, with the S-ECC group containing higher levels of known cariogenic organisms.


Thalidomide Combined with Chemotherapy in Treating Patients with Advanced lung Cancer.
To evaluate efficacy and toxicity in patients with advanced lung cancer, including non-small cell and small cell variants (NSCLC and SCLC), treated with thalidomide plus chemotherapy. Fourteen patients with advanced lung cancer were scheduled to receive chemotherapy combined with thalidomide. All patients in this study received thalidomide (100 mg orally per night before sleeping, produced by Changzhou Pharmaceutical Factory Co.Ltd) after the start of chemotherapy for at least 14 days. Chemotherapy was administered according to the condition of patients. After at least 14 days of treatment, efficacy and toxicity were evaluated. There were 6 female and 8 male patients with advanced lung cancer recruited into this study, including 2 with SCLC and 12 with NSCLC. The median age was 56.7 (44-65) years. Progressive disease was observed in 12 patients (12/14), and stable disease in 2 (2/14). Grade 1 to 2 myelosuppression was observed in 4/14 patients, and Grade 1 to 2 elevation of hepatic enzymes was recorded in 5/14 patients. Adverse effects on the gastrointestinal tract were documented in 2/14 patients, all beingGrade 1. No Grade 3-4 toxicity was recorded. No treatment related deaths occurred. Our results demonstrate that thalidomide combined with chemotherapy is mildly effective and safe for treating patients with advanced lung cancer. However, further evaluation of this combination is warranted.


Age-related variations of left ventricular endocardial and midwall function in healthy infants, children, and adolescents.
In pediatric age echocardiographic evaluation of left ventricular systolic function is usually based on indexes obtained by measurements at the endocardial level. In the presence of ventricular hypertrophy this may lead to an overestimation of systolic function. The aim of this study was to assess the developmental changes of left ventricular systolic mechanics measured at the endocardial and midwall levels. In 239 normal subjects divided into six age groups we measured left ventricular end-diastolic volume, mass and mass/volume ratio, fractional shortening, and rate-corrected mean velocity of circumferential shortening at the endocardial and midwall levels. Endocardial meridional end-systolic stress and midwall circumferential end-systolic stress were considered as indexes of afterload. Relations of extent and velocity of fiber shortening to afterload at the endocardial and midwall levels were used to assess left ventricular contractility. Blood pressure, left ventricular afterload, volume and mass increased, whereas the mass/volume ratio remained stable during growth. Fractional shortening and mean velocity of circumferential shortening at the endocardial level decreased and showed an inverse relation to afterload. Midwall fractional shortening and rate-corrected mean velocity of circumferential shortening were lower during the first months and did not change during the first year of life. Left ventricular volume and mass increase with age, mass/volume ratio remains almost constant while afterload increases. Endocardial systolic function indexes are higher in the first period of life, due to low afterload and increased mass/volume ratio. In the first months of life the left ventricular myocardium shows a greater sensitivity to changes in afterload and a reduced contractility measured at the midwall level.


An answer to chronicity in the Basque Country: primary care-based population health management.
Chronic conditions have an impact on individuals since they represent a restraint on quality of life, functional status, and productivity of people who suffer from them but they also compromise the sustainability of health systems. In 2010, the Strategy for Tackling the Challenge of Chronicity in the Basque Country was published. It contains policies and projects aimed at reinventing the health delivery model with the purpose of improving the quality of care for chronic patients and advancing toward a more sustainable, proactive, and integrated model. We present 3 projects here: population stratification, integrated care initiatives, and innovation from health care staff.


[Penile cancer and human papillomavirus infection].
Human papillomavirus (HPV) infection is one of the major risk factors for penile cancer. This article presents an overview on the biological characteristics of HPVs, HPV infection in penile cancer, possible carcinogenic mechanisms of HPV, prognostic value of HPV in penile cancer, and HPV vaccine.


High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high-risk CTV sizes.
To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated. Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and < 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed. Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (> 40 cc) when using T&O applicator approach. MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator.


The biophysics and biomechanics of cryoballoon ablation.
Recent clinical and preclinical studies have demonstrated that cryothermal ablation using a balloon catheter (Artic Front®, Medtronic CryoCath LP, Pointe-Claire, Canada) provides an effective means of achieving pulmonary vein isolation. This review explores the biophysics and biomechanics of cryoballoon ablation. Components of the cryoballoon catheter system are examined, mechanisms of cryothermal injury are summarized, and potential advantages of cryoballoon technology over standard radiofrequency ablation in isolating pulmonary veins are discussed. Practical aspects of biophysics and biomechanics relevant to the clinical electrophysiologist are emphasized, particularly with regards to the selection of the most appropriate cryoballoon catheter and minimizing peri-procedural complications.


The evolving management of small bowel adenocarcinoma.
Small bowel adenocarcinoma (SBA) is rare despite the fact that the small bowel represents the longest part and has the largest surface of all alimentary tract sections. Its incidence is 50-fold lower than that of colorectal carcinoma. It is often diagnosed at an advanced stage due to atypical and late symptoms, its low index of suspicion, difficult endoscopic access and poor detection by radiological imaging, resulting in impaired outcome. Due to its rarity and being molecularly a unique intestinal cancer, data regarding its optimal management are relatively sparse. A PubMed search was performed to identify relevant manuscripts that were recently published. Emerging data regarding the pathogenesis, the diagnosis and the treatment of SBA that resulted from recent research are discussed in this comprehensive review. Genomic analysis has demonstrated that SBA is a molecularly unique intestinal cancer. Double balloon enteroscopy and capsule endoscopy are novel techniques which may result in earlier diagnosis and consequently in improvement of the generally poor prognosis. For clinically localized disease, the quality of surgery has recently been defined, with removal of at least 8-10 lymph nodes correlating with improved prognosis. Moreover, adjuvant chemotherapy seems to improve outcome of stage III disease. The combination of a fluoropyrimidine and oxaliplatin appears to be the most effective systemic chemotherapy for disseminated disease. Genomic profiling can identify potentially targetable genomic alterations in a significant proportion of SBA patients. The role of administration of targeted agents or immune checkpoint inhibitors is still unknown and subject of ongoing clinical trials. In the common case of peritoneal metastases, recent studies have shown that cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy may be an attractive treatment option in selected patients. SBA is a rare and unique malignancy, whose diagnostic approach and treatment are evolving, resulting in improved outcome.


Provision of emergency obstetric care at secondary level in a conflict setting in a rural area of Afghanistan - is the hospital fulfilling its role?
Provision of Emergency Obstetric and Neonatal Care (EmONC) reduces maternal mortality and should include three components: Basic Emergency Obstetric and Neonatal Care (BEmONC) offered at primary care level, Comprehensive EmONC (CEmONC) at secondary level and a good referral system in-between. In a conflict-affected province of Afghanistan (Khost), we assessed the performance of an Médecins Sans Frontières (MSF) run CEmONC hospital without a primary care and referral system. Performance was assessed in terms of hospital utilisation for obstetric emergencies and quality of obstetric care. A cross-sectional study using routine programme data (2013-2014). Of 29,876 admissions, 99% were self-referred, 0.4% referred by traditional birth attendants and 0.3% by health facilities. Geographic origins involved clustering around the hospital vicinity and the provincial road axis. While there was a steady increase in hospital caseload, the number and proportion of women with Direct Obstetric Complications (DOC) progressively dropped from 21% to 8% over 2 years. Admissions for normal deliveries continuously increased. In-hospital maternal deaths were 0.03%, neonatal deaths 1% and DOC case-fatality rate 0.2% (all within acceptable limits). Despite a high and ever increasing caseload, good quality Comprehensive EmONC could be offered in a conflict-affected setting in rural Afghanistan. However, the primary emergency role of the hospital is challenged by diversion of resources to normal deliveries that should happen at primary level. Strengthening Basic EmONC facilities and establishing an efficient referral system are essential to improve access for emergency cases and increase the potential impact on maternal mortality.


Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone.
Use of adeno-associated virus (AAV) to transduce genes into skeletal muscles can be associated with T-cell responses to viral capsid and/or to transgenic protein. Intramuscular mononuclear cell infiltrates primarily consisting of CD8+ T cells and also containing FOXP3+ regulatory T cells were present in rhesus macaque skeletal muscle treated with rAAVrh74.MCK.GALGT2 by vascular delivery. Administration of oral prednisone prior to AAV gene delivery and throughout the study reduced such infiltrates by 60% at 24 weeks post AAV delivery compared with AAV-treated animals not receiving prednisone, regardless of the presence of pre-existing AAV serum antibodies at the time of treatment. The majority of CD8+ T cells in AAV-treated muscles expressed activated caspase 3 and programmed cell death protein 1 (PD1), suggesting ongoing programmed cell death. AAV-transduced skeletal muscles also had elevated expression of programmed death ligand 2 (PDL2) on skeletal myofibers, and this increase in expression extended to muscles where transgene was not overexpressed. These data demonstrate that prednisone can reduce the extent of intramuscular T-cell infiltrates in AAV-treated muscles, which may aid in achieving long-term transgene expression, as may the induction of PDL2 expression on skeletal myofibers to promote PD1-mediated programmed T-cell death.


Recent advances in cellular degradation and nuclear control of leaf senescence.
Senescence is the final stage of plant growth and development, and is a highly regulated process at the molecular, cellular, and organismal levels. When triggered by age, hormonal, or environmental cues, plants actively adjust their metabolism and gene expression to execute the progression of senescence. Regulation of senescence is vital for the reallocation of nutrients to sink organs, to ensure reproductive success and adaptations to stresses. Identification and characterization of hallmarks of leaf senescence are of great importance for understanding the molecular regulatory mechanisms of plant senescence, and breeding future crops with more desirable senescence traits. Tremendous progress has been made in elucidating the genetic network underpinning the metabolic and cellular changes in leaf senescence. In this review, we focus on three hallmarks of leaf senescence - chlorophyll and chloroplast degradation, loss of proteostasis, and activation of senescence-associated genes (SAGs), and discuss recent findings of the molecular players and the crosstalk of senescence pathways.


Risk Factors for Daytime or Combined Incontinence in Children with Cerebral Palsy.
We identify risk factors for daytime or combined urinary incontinence in children with cerebral palsy. A cross-sectional case-control study was conducted including children with cerebral palsy with or without daytime or combined urinary incontinence from the CP-Reference Center at Ghent University Hospital and 2 associated special education schools. Factors were subdivided in 3 clusters of demographic and general medical data, cerebral palsy classification, and bladder and bowel dysfunction. Data were obtained using uroflowmetry with electromyography testing, a nonvalidated questionnaire and bladder diaries. Univariate and multivariate analyses were performed for variables and clusters, respectively. A final associative logistic model including all clusters was developed. The study included 34 incontinent children and 45 continent children. Daytime or combined urinary incontinence was associated with intellectual disability (OR 7.69), swallowing problems (OR 15.11), use of external aids (OR 27.50) and use of laxatives (OR 13.31). Daytime or combined urinary incontinence was positively associated with dyskinesia (OR 5.67) or combined spasticity and dystonia (OR 4.78), bilateral involvement (OR 4.25), Gross Motor Function Classification System level IV (OR 10.63) and V (OR 34.00), and severe impairment in manual (OR 24.27) or communication skills (OR 14.38). Lower maximum voided volume (OR 0.97) and oral fluid intake (OR 0.96) influenced daytime or combined urinary incontinence negatively. Pathological uroflow curves were not significantly associated with incontinence. The final model defined functional impairment, intellectual disability and oral fluid intake as predictive factors for daytime or combined urinary incontinence. Risk analysis revealed functional impairment, intellectual disability and fluid intake as important factors influencing continence in a child with cerebral palsy.


Effect of intravenous infusions of 12-O-tetradecanoylphorbol-13-acetate (TPA) in patients with myelocytic leukemia: preliminary studies on therapeutic efficacy and toxicity.
Studies by several investigators have shown that 12-0-tetradecanoylphorbol-13-acetate (TPA) is an extraordinarily potent stimulator of differentiation of cultured human promyelocytic leukemia cells in vitro. In the present study, TPA was administered to humans by i.v. infusion without irreversible toxicity, and it was shown to have pharmacological activity for the treatment of myelocytic leukemia in patients refractory to cytosine arabinoside (Ara C), retinoic acid, and other antileukemic drugs. Marked decreases in bone marrow myeloblasts as well as temporary remission of disease symptoms were observed when TPA was administered alone or in combination with vitamin D3 and Ara C. Additional studies with TPA after the determination of optimum dosing regimens are needed to determine whether long-lasting or permanent remissions of myelocytic leukemia can be achieved. Transient and reversible side effects were observed after a 1-mg i.v. dose of TPA, but these adverse effects became less intense or disappeared when a lower dose of TPA was used. The results of this study indicate a therapeutic effect of TPA in patients with myelocytic leukemia.


Well-being at onset of hormone replacement therapy: comparison between two continuous combined regimens.
To compare the effect on well-being of two continuous combined hormone replacement therapies (HRTs) in women starting treatment ('starters') and women switching from mainly sequential HRT ('switchers'). This was a randomized, double-blind, 1-month trial, in which 249 postmenopausal women were treated with either conjugated estrogen plus medroxyprogesterone acetate (CE/MPA 0.625 mg/5 mg) or 17beta-estradiol plus norethisterone acetate (E2/NETA 2 mg/1 mg) continuously. Twelve items for measuring climacteric symptoms and well-being were reported daily on a validated symptom scale. Women taking CE/MPA reported lower scores for breast tenderness (p = 0.005), depression (p = 0.019), irritability (p = 0.004) and tension (p = 0.048), compared with women taking E2/NETA. Compared with pretreatment, both groups developed side-effects during the first week: breast tenderness, swelling and depression (p < 0.05). Starters, but also switchers, improved in sweats (p < 0.001 and p = 0.030). Compared with pretreatment ratings, switchers reported higher scores for breast tenderness (p < 0.001), depression (p = 0.050) and negative effects on daily life (p < 0.001), whereas starters reported only physical side-effects (p < 0.05). A history of premenstrual syndrome (PMS) predicted high scores for swelling (p = 0.023), depression (p = 0.024), tension (p = 0.009), irritability (p = 0.027), headache (p < 0.001) and negative effects on daily life (p < 0.001). CE/MPA 0.625 mg/5 mg is better tolerated than E2/NETA 2 mg/1 mg, and starters react differently from switchers. Side-effects occur more quickly than benefits with HRT, and are more frequent in women with previous PMS.


Targeting Endothelial Barrier Dysfunction Caused by Circulating Bacterial and Mitochondrial N-Formyl Peptides With Deformylase.
Despite recent advances in our understanding of the mechanisms underlying systemic inflammatory response syndrome (SIRS) and sepsis, the current therapeutic approach to these critically ill patients is centered around supportive care including fluid resuscitation, vasopressors and source control. The incidence of SIRS and sepsis continues to increase in the United States and patients die due to failure to respond to the traditional therapies of nitric oxide blockade, adrenergic agonists, etc. Bacterial and mitochondrial N-formyl peptides (NFPs) act as damage-associated molecular patterns and activate the innate immune system through formyl peptide receptors (FPR) located in immune and non-immune cells, including the vascular endothelium. The resulting inflammatory response manifests as capillary leak, tissue hypoperfusion and vasoplegia, partially due to endothelium barrier breakdown. Potential strategies to prevent this response include decreasing NFP release, breakdown of NFPs, and blocking NFPs from binding FPR. We propose the use of deformylase, the degrading enzyme for NFPs, as potential therapeutic approach to prevent the deleterious effects of NFPs in SIRS and sepsis.


Combination of hypoxic preconditioning and postconditioning does not induce additive protection of ex vivo human skeletal muscle from hypoxia/reoxygenation injury.
We previously demonstrated that hypoxic preconditioning (HPreC) or postconditioning (HPostC) protected ex vivo human skeletal muscle from hypoxia/reoxygenation injury. Here, we investigated if combined HPreC and HPostC could convey additive protection. Human rectus abdominis muscle strips were cultured in normoxic Krebs buffer for 5 hours (control) or in 3 hours hypoxic/2 hours normoxic buffer (treatment groups). HPreC and HPostC were induced by 1 cycle of 5 minutes hypoxia/5 minutes reoxygenation immediately before or after 3 hours hypoxia, respectively. Muscle injury, viability, and adenosine triphosphate (ATP) synthesis were assessed by measuring lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction, and ATP content, respectively. Hypoxia/reoxygenation caused lactate dehydrogenase to increase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction and ATP content to decrease (P < 0.05; n = 7). HPreC, HPostC, and combination of both were equally effective in protection of muscle from hypoxia/reoxygenation injury. Atractyloside (5 × 10 M), a mitochondrial permeability transition pore opener, abolished the protective effect of HPreC or HPostC. We conclude that HPreC and HPostC protect ex vivo human skeletal muscle against hypoxia/reoxygenation injury by closing the mitochondrial permeability transition pore. For that reason, they are equally effective and do not demonstrate an additive effect. Moreover, the potent effect of HPostC indicates ischemic postconditioning as an effective clinical intervention against reperfusion injury in autogenous skeletal muscle transplantation and replantation surgery.


Antibiotic action on phagocytosed bacteria measured by a new method for determining viable bacteria.
Antibiotics such as rifampin that act on phagocytosed bacteria have clinical advantages. The investigation of such intraphagocytic activity of antibiotics is, however, hampered by the time-consuming and cumbersome procedures necessary for enumerating viable bacteria. We have developed a semiautomatic biophotometric method for this purpose that permits the processing of relatively large numbers of samples. Using this method with Staphyloccus aureus Wood 46 as a test organism, we studied the dose dependence of the activities of a number of antibiotics against intraphagocytic bacteria. We could confirm the very good intracellular activity of rifampin. Its activity at low concentrations was slightly better against intracellular than against extracellular bacteria. In contrast, clindamycin and erythromycin, both of which have been reported to accumulate within phagocytes, did not exhibit a correspondingly enhanced intracellular activity, erythromycin being active intracellularly only at high concentrations. Clindamycin and vancomycin were effective against intracellular organisms, but only at relatively high concentrations owing to their low bactericidal activity against S. aureus Wood 46. Penicillin G, ampicillin, gentamicin, and streptomycin exhibited no useful intracellular activity. These results demonstrate that radioactive accumulation studies of antibacterial agents are not sufficient to show intracellular activity. Intracellular activity must be demonstrated in a functional test, preferably with graded concentrations of the test substance.


Stabilizing effect of precontracted neck musculature in whiplash.
This study investigated the effect of neck muscle precontraction in aware occupants in whiplash. Head angulation relative to T1 and facet joint capsular ligament distractions were compared between aware and unaware occupants. To quantify changes in facet joint capsular ligament distractions between aware occupants with precontracted neck muscles and unaware occupants with reflex muscle contraction. Clinical studies have reported that patients aware of the impending impact had decreased symptom intensity and faster recovery after whiplash. To date, no study has investigated the effects of precontracted neck musculature on localized spinal soft tissue distortions in whiplash. Aware occupants with precontracted neck muscles and unaware occupants with reflex muscle contraction in whiplash were simulated using a validated computational model. Muscle contraction attained maximum levels before impact in the aware occupant and implemented reflex delay, electromechanical delay, and finite muscle rise time in the unaware occupant. Precontraction of neck muscles in aware occupants resulted in 63% decreased maximum head angles, elimination of cervical S-curvature, and up to 75% decrease in maximum facet joint capsular ligament distractions. Occupants aware of an impending whiplash impact with precontracted neck muscles can markedly reduce overall head-neck and spinal motions. It is our theory that this would reduce whiplash injury likelihood.


Verification of temporal scheduling constraints in clinical practice guidelines.
The computerization of clinical practice guidelines is a significant scientific challenge for the medical informatics community. One frequently reported factor hindering this objective is the existence of deficiencies within guideline knowledge. In this paper, we focus on the detection of flaws within temporal scheduling constraints. Temporal scheduling constraints are important elements of therapy management, and are frequently incorporated in clinical practice guidelines. We present a suitable verification method that is based on calculating the minimal network of temporal constraints on the execution of guideline activities. Our method serves three purposes: (1) it checks whether temporal scheduling constraints are consistent with scheduling constraints implied by control flow operators and the hierarchical structuring of a guideline; (2) it yields suggestions for an equivalent, yet more explicit representation of non-minimal constraints; (3) it can be used by the guideline interpreter to assemble feasible time intervals for the execution of each guideline activity. We evaluate our approach by applying it to a guideline specified in the Asbru language. For this purpose, we implemented a prototype verifier. Although we concentrate on the guideline representation language Asbru as the demonstration medium of our method within this paper, our approach can be reused to verify several alternative guideline representation formats.


[A clinical study on the diagnosis of early rheumatoid arthritis using bone imaging with 99mTc-MDP].
This study aimed to explore the usefulness of 99mTechnetium methylenediphosphonate (99mTc-MDP) bone imaging in diagnosticating rheumatoid arthritis (RA). In 66 patients with RA, 99mTc-MDP whole body bone imaging, feet and hands regional bone imaging and ROI were performed. And from each patient, X-ray film, rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were taken for examination. By the use of 99mTc-MDP, abnormal bone images were observed in 55 cases of RA; the total positive rate of incidence (83.3%) was significantly higher than those by use of X-ray (45.5%), RF (51.5%), CRP (63.6%) and ESR (69.7%); the positive rates of imaging with 99mTc-MDP in the 55 cases of RA (divided into 4 groups according to the course of disease; namely, < 1,1-, 5- and >10-year groups) were 75.0%, 88.9%, 92.3% and 100.0% respectively, whereas the positive rates of those year-groups by use of X-ray were 10.7%, 33.3%, 84.6%, 100.0% respectively; comparison of the two methods, showed statistically significant difference: P<0.01 (< 5-year group); P >0.05 (> 5-year group). In 177 joint lesions detected by bone images, 144 lesions (81.4%) were symmetric, and 33 lesions (18.6%) were single. The most frequently detected lesions were at metacarpophalangeal joints or interphalangeal and wrist joints, metatarsophalangeal or ankle joints, and knee joints. We have noticed that 99mTc-MDP bone imaging can elevate the detectability at the early stage of RA, so it is of value for the treatment of RA.


Characteristics of lower extremity work during the impact phase of jumping and weightlifting.
Jumping and weightlifting tasks involve impact phases, where work is performed by the lower extremity to absorb energies present at contact. This study compared the lower extremity kinematic and kinetic strategies to absorb energy during the impact phase of jumping and weightlifting activities. Ten women experienced in jumping and weightlifting performed 4 tasks (landing from a jump, drop landing, clean, and power clean) in a motion analysis laboratory. Work performed at the hip, knee, and ankle were calculated during the landing and receiving phases of jumping and weightlifting tasks, respectively. Additionally, segment and joint kinematics and net joint moments were determined. The most lower extremity work was performed in the clean and drop landing, followed by landing from a jump, and the least work was performed in the power clean (p < 0.05). For all tasks, work performed by the knee extensors was the greatest contributor to lower extremity work. Knee extensor net joint moment was greater in the power clean than jump and drop landings, and greater in the clean than all other tasks (p < 0.05). Knee flexion angle was not different between the power clean and jump landing (p > 0.05) but greater in the drop landing and clean (p < 0.05). A common characteristic of the impact phase of jumping and weightlifting tasks is a large contribution of knee extensor work. Further, the correspondence in kinematics between impact phases of jumping and weightlifting tasks suggests that similar muscular strategies are used to perform both types of activities. Weightlifting tasks, particularly the clean, may be important exercises to develop the muscular strength required for impact actions due to their large knee extensor net joint moments.


[Clinical analysis of 21 cases with short fetal femur in the third trimester].
Objective: To analyze the clinical features and to explore the etiology of short fetal femur during the third trimester. Methods: From January 2010 to June 2016, 21 singleton pregnancies with short fetal femur detected by ultrasonography during the third trimester were referred to the Chinese PLA General Hospital. Clinical data were collected, karyotype or single nucleotide polymorphism microarray was carried out to detect chromosomal abnormalities, and FGFR3 c.1138G>A mutation detection was carried out to detect achondroplasia (ACH) via invasive procedure, respectively. The deviation of femur length from the mean value of the gestational age in ultrasonography was expressed as the Z-score. The difference between ACH and isolated short femur (ISF, in the absence of associated structure abnormality or genetic abnormality) was then explored. Results: In the 21 fetuses, 11 had abnormal genetic test results(52%, 11/21), including 9 cases of ACH, 1 case of Ellis-van Creveld Syndrome and 1 case of Pallister-Killian syndrome. In the 10 ISF fetuses (48%, 10/21), 3 cases were fetal growth restriction, 1 was normal small for gestational age infant and 6 cases were unexplained. The median Z-scores for 9 cases of ACH and 10 cases of ISF in the third trimester were -5.04, -3.20, respectively. The short femur in ACH was more severe than in ISF (P=0.005) in the third trimester. Conclusions: The etiology of short fetal femur is complicated, including skeletal dysplasia, chromosomal abnormality, fetal growth restriction, as well as normal variants during fetal development. Genetic test should be considered during the antenatal consultation.


Development of ion source with a washer gun for pulsed neutral beam injection.
A new type of economical neutral beam source has been developed by using a single washer gun, pulsed operation, and a simple electrode system. We replaced the conventional hot filaments for arc-discharge-type plasma formation with a single stainless-steel washer gun, eliminating the entire dc power supply for the filaments and the cooling system for the electrodes. Our initial experiments revealed successful beam extraction up to 10 kV and 8.6 A, based on spatial profile measurements of density and temperature in the plasma source. The system also shows the potential to control the beam profile by controlling the plasma parameters in the ion accumulation chamber.


Analysis of tablet compaction. I. Characterization of mechanical behavior of powder and powder/tooling friction.
In this first of two articles on the modeling of tablet compaction, the experimental inputs related to the constitutive model of the powder and the powder/tooling friction are determined. The continuum-based analysis of tableting makes use of an elasto-plastic model, which incorporates the elements of yield, plastic flow potential, and hardening, to describe the mechanical behavior of microcrystalline cellulose over the range of densities experienced during tableting. Specifically, a modified Drucker-Prager/cap plasticity model, which includes material parameters such as cohesion, internal friction, and hydrostatic yield pressure that evolve with the internal state variable relative density, was applied. Linear elasticity is assumed with the elastic parameters, Young's modulus, and Poisson's ratio dependent on the relative density. The calibration techniques were developed based on a series of simple mechanical tests including diametrical compression, simple compression, and die compaction using an instrumented die. The friction behavior is measured using an instrumented die and the experimental data are analyzed using the method of differential slices. The constitutive model and frictional properties are essential experimental inputs to the finite element-based model described in the companion article.


Chemically directed immobilization of nanoparticles onto gold substrates for orthogonal assembly using dithiocarbamate bond formation.
Dithiocarbamate-mediated bond formation combined with soft lithography was used for the selective immobilization of amine-functionalized silica nanoparticles on gold substrates. The available amine groups on the upper surface of the immobilized silica nanoparticles were further utilized for postdeposition of additional materials including particles, dyes, and biomolecules. The robustness of dithiocarbamate-mediated immobilization enables orthogonal assembly on surfaces via selective removal of the masking thiol ligands using iodine vapor etching followed by further functionalization.


Amyloid Beta peptides differentially affect hippocampal theta rhythms in vitro.
Soluble amyloid beta peptide (A β ) is responsible for the early cognitive dysfunction observed in Alzheimer's disease. Both cholinergically and glutamatergically induced hippocampal theta rhythms are related to learning and memory, spatial navigation, and spatial memory. However, these two types of theta rhythms are not identical; they are associated with different behaviors and can be differentially modulated by diverse experimental conditions. Therefore, in this study, we aimed to investigate whether or not application of soluble A β alters the two types of theta frequency oscillatory network activity generated in rat hippocampal slices by application of the cholinergic and glutamatergic agonists carbachol or DHPG, respectively. Due to previous evidence that oscillatory activity can be differentially affected by different A β peptides, we also compared Aβ 25-35 and Aβ 1-42 for their effects on theta rhythms in vitro at similar concentrations (0.5 to 1.0 μ M). We found that Aβ 25-35 reduces, with less potency than Aβ 1-42, carbachol-induced population theta oscillatory activity. In contrast, DHPG-induced oscillatory activity was not affected by a high concentration of Aβ 25-35 but was reduced by Aβ 1-42. Our results support the idea that different amyloid peptides might alter specific cellular mechanisms related to the generation of specific neuronal network activities, instead of exerting a generalized inhibitory effect on neuronal network function.


Using activity-based therapy for individuals with spinal cord injury or disease: Interviews with physical and occupational therapists in rehabilitation hospitals.
To understand if and how physical therapists (PTs) and occupational therapists (OTs) use activity-based therapy (ABT) and its associated technologies for the rehabilitation of individuals living with spinal cord injury or disease (SCI/D) in Canadian rehabilitation hospital settings. Qualitative study. Through rehabilitation hospitals participating in the Rick Hansen Spinal Cord Injury Registry, we recruited licensed OTs and PTs to participate in focus groups. Twelve PTs and ten OTs from nine sites across eight provinces participated. To inform the development of a semi-structured interview guide, we used the Theoretical Domains Framework. To analyze the data, we used interpretive description. We identified three themes that influenced therapists' use of ABT and associated technologies for SCI/D rehabilitation. (1) Therapists' decision-making approach to ABT and technology. Therapist roles, site-specific dynamics and goal setting influenced decision-making. Assuming roles such as mentor, liaison and advocate led to more ABT use. Site-specific dynamics concerned levels of ABT knowledge, teamwork, and staffing. In hospital rehabilitation, there was competition between discharge and neurorecovery goals. (2) Therapist perceived individual factors. Patient factors either increased (i.e. patients' motivation, self-advocacy) or prevented (i.e. mourning period, tolerance) the likelihood that ABT was introduced by therapists. (3) ABT and equipment access. Technology was used for ABT in a variety of ways. Access was affected by visible (e.g. equipment cost) and invisible barriers (e.g. departmental relations). The use of ABT and its associated technologies in Canadian rehabilitation hospitals is variable. Ongoing education could be offered, and site-specific implementation strategies could be developed, to promote ABT use.


Immunophenotypical Switch versus Tumor Heterogeneity in a Patient with HIV-Associated Diffuse Large B-Cell Lymphoma.
Patients with HIV/AIDS have a higher risk of developing aggressive B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL). Lymphomas are rather heterogeneous in nature and in a few cases can switch their genetic or immunohistochemical phenotype, transform into other lymphomas or carry more than one malignant clone. In this report, we present the case of a 47-year-old man with HIV infection who was diagnosed with an apparent low-risk, early-stage DLBCL, but became refractory to therapy while undergoing treatment with rituximab-containing chemotherapy. We postulate that the development of his refractory disease occurred in the context of an immunohistochemical switch or the surge of a clone refractory to therapy. This phenomenon was not associated with a superinfection with EBV or HHV-8.


Acute-phase protein levels, diarrhoea, Trichuris trichiura and maternal education are predictors of serum retinol: a cross-sectional study of children in a Dhaka slum, Bangladesh.
The objectives of the present study were to identify predictors of serum retinol concentration as well as to assess the prevalence of low serum retinol concentration, in both the whole population after correcting for the effect of serum C-reactive protein (CRP) (using multiple categories), and the healthy subgroup. A cross-sectional study of 579 apparently healthy children, aged 3-7 years from a Dhaka slum, Bangladesh, was conducted. The effects of age, gender, serum CRP and alpha1-antichymotrypsin, reported morbidity (during the previous 2 weeks), Ascaris lumbricoides and Trichuris trichiura infections, parental education, wasting, stunting and underweight on serum retinol were estimated using multiple linear regression. The mean serum retinol concentration was 0.84 (sd 0.27) micromol/l. Elevated serum CRP levels, reported diarrhoea, reported nasal discharge and T. trichiura infection were negative predictors of serum retinol, whereas maternal education was a positive predictor. Compared with a serum CRP level of < 1 mg/l, CRP levels of 2 to < 5, 5 to < 10 and > or = 10 mg/l were associated with 0.12, 0.16 and 0.32 micromol/l lower serum retinol, respectively. The prevalence of low serum retinol (< 0.70 micromol/l) fell from 31.2 % to 15.6 % in the whole population, after correcting for the effect of CRP, and was 20.1 % in the healthy subgroup (CRP < 2 mg/l). The prevalence of low serum retinol was high but overestimated due to the effect of CRP. Interventions are needed to address low serum retinol in Bangladesh. Controlling diarrhoea, nasal discharge and T. trichiura infection and improving maternal education may be important interventions. The use of multiple categories of acute-phase proteins and cut-off values that indicate elevated levels need further research.


More of what? Issues raised by the Fort Bragg study.
The sobering findings of the Fort Bragg study illustrate why ambitious demonstration projects must be combined with objective outcome evaluations. The study does suggest that "more is not always better" (L Bickman, 1996), but more of what? Little is known about the specific interventions that were combined to form the Fort Bragg system of care, so the study does not really reveal what failed or what needs to be changed. Moreover, there is no evidence that the specific treatments used had any empirical support. Combining and systematizing various treatments may not produce improved outcomes if the treatments are not effective in the first place. Costly demonstration programs that combine untested treatments may be a poor investment. A better strategy may be to develop and test an array of well-documented treatments for an array of child and family problems, creating the building blocks needed for effective systems of care in the future.


Analytical expressions for the log-amplitude correlation function for plane wave propagation in anisotropic non-Kolmogorov refractive turbulence.
An analytical expression for the log-amplitude correlation function for plane wave propagation through anisotropic non-Kolmogorov turbulent atmosphere is derived. The closed-form analytic results are based on the Rytov approximation. These results agree well with wave optics simulation based on the more general Fresnel approximation as well as with numerical evaluations, for low-to-moderate strengths of turbulence. The new expression reduces correctly to the previously published analytic expressions for the cases of plane wave propagation through both nonisotropic Kolmogorov turbulence and isotropic non-Kolmogorov turbulence cases. These results are useful for understanding the potential impact of deviations from the standard isotropic Kolmogorov spectrum.


Tips and Trends to Start the New Year.
With the New Year comes the opportunity to set goals and advance training and development opportunities for leaders. This article presents five tips and five trends that serve as prognosticators for the coming year, including tips to influence time management and leadership impact and trends, such as sexual harassment training and "soft" skills development, which are now core skills for team success. A shift from hierarchical structures to network- and relationship-centered webs for advanced problem solving is also projected. J Contin Educ Nurs. 2018;49(1):7-9.


Codelivery of a miR-124 Mimic and Obatoclax by Cholesterol-Penetratin Micelles Simultaneously Induces Apoptosis and Inhibits Autophagic Flux in Breast Cancer in Vitro and in Vivo.
Penetratin is a classical cell-penetrating peptide with the potential to assist in the transmembrane delivery of proteins or drugs. However, the synthesis and application of cholesterol-penetratin (Chol-P) conjugates as nonviral delivery systems for microRNAs or drugs have not previously been reported. In this study, the amphiphilic Chol-P was shown to self-assemble into micelles and efficiently deliver miR-124 and obatoclax. The codelivered miR-124-M-Oba had a homogeneous particle size and a positive zeta potential. Treatment with miR-124 mincreased cytotoxicity, and cell proliferation, was promoted by miR-124 inhibitor-loaded micelles in MCF-7 human breast cancer cells. Moreover, the inhibitory effects on cell proliferation, colony formation, and cell migration were increased in the miR-124-M-Oba group compared to the miR-124-M group. miR-124-M-Oba induced higher levels of mitochondrial apoptosis via Bax and caspase-9 activation. In addition, we found that the cationic Chol-P and miR-124-M could potently induce autophagy, and miR-124 was degraded in the corresponding autophagolysosomes. The obatoclax encapsulated in miR-124-M-Oba could inhibit the degradation of miR-124 and p62 in autophagolysosomes, which consequently maintained the concentration of miR-124 in breast cancer cells. Furthermore, miR-124-M-Oba potently inhibited tumor growth in subcutaneous xenograft breast cancer models. In summary, the miR-124-M-Oba prepared in this work showed improved apoptosis induction and autophagic flux inhibitory effects in MCF-7 cells, and miR-124-M-Oba may have potential applications in breast cancer therapy.