Observation of a Flowing Duct in the Abdominal Wall by Using Nanoparticles

The primo vascular system (PVS) is being established as a circulatory system that corresponds to acupuncture meridians. There have been two critical questions in making the PVS accepted as a novel liquid flowing system. The first one was directly to show the flow of liquid in PVS and the second one was to explain why it was not observed in the conventional histological study of animal tissues. Flow in the PVS in the abdominal cavity was previously verified by injecting Alcian blue into a primo node. However, the tracing of the dye to other subsystems of the PVS has not been done. In the current work we injected fluorescent nanoparticles (FNPs) into a primo node and traced them along a primo vessel which was inside a fat tissue in the abdominal wall. Linea alba is a white middle line in the abdominal skin of a mammal and a band of fat tissue is located in parallel to the linea alba in the parietal side of the abdominal wall of a rat. In this fat band a primo vessel runs parallel to the prominent blood vessels in the fat band and is located just inside the parietal peritoneum. About the second question on the reason why the PVS was not in conventional histological study the current work provided the answer. Histological analysis with hematoxyline and eosine, Masson’s trichrome, and Toluidine blue could not discriminate the primo vessel even when we knew the location of the PVS by the trace of the FNPs. This clearly explains why the PVS is hard to observe in conventional histology: it is not a matter of resolution but the contrast. The PVS has very similar structure to the connective tissues that surround the PVS. In the current work we propose a method to find the PVS: Observation of mast cell distribution with toluidine blue staining and the PN has a high density of mast cells, while the lymph node has low density.     

Reasons for Missing Antiretroviral Therapy: Results from a Multi-Country Study in Tanzania,Uganda, and Zambia

Objectives

To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence.

Methods

Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients’ medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months.

Results

Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2–7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1–1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms.

Conclusions

Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes.     

DNA sequencing reveals unexpected Recent diversity and an ancient dichotomy in the American marsupial genus Marmosops (Didelphidae: Thylamyini)

To assess species‐level diversity in the didelphid marsupial genus Marmosops, we obtained sequence data from the mitochondrial cytochrome b (CYTB) gene from > 200 specimens, including exemplars of every currently recognized species together with multiple specimens of all geographically widespread forms. Analyses of these data using the general mixed Yule coalescent (GMYC) model suggest that the genus could be twice as speciose as currently recognized, but putative species identified by the GMYC criterion require careful evaluation using other data. To assess phylogenetic relationships within Marmosops, we additionally sequenced a large fragment of the breast cancer activating 1 (BRCA1) gene from one specimen each of the putative species identified by the GMYC analyses of CYTB. Maximum likelihood and Bayesian analyses of a concatenated gene (CYTB + BRCA1) matrix revealed a basal dichotomy between two ancient, morphologically diagnosable clades with apparently distinct distributions and adaptive phenotypes. We describe those clades as subgenera and assign 12 nominal taxa to Sciophanes subgen. nov. (with type species Marmosops parvidens) and 27 nominal taxa to the nominotypical subgenus (with type species Marmosops incanus).     

Aging exo-enzymes can create temporally shifting,temperature-dependent resource landscapes for microbes

The rate at which catalytic capacity of microbial exo-enzymes degrades post-exudation will influence the time during which return on microbes’ investment in exo-enzyme production can be realized. Further, if exo-enzyme degradation rates vary across exo-enzymes, microbial investment returns may vary by element across time. We quantify how aging of two soil organic matter (SOM)-decaying enzymes (β-D-cellobioside, BGase; and N-acetyl-β-D-glucosaminide, NAGase) influences enzyme-substrate V _max at multiple temperatures (5, 15, 25 °C), and compute how enzyme age influences relative availabilities of C and N. Both BGase and NAGase exhibited similar, exponential declines in catalytic rate with age at 25 °C (0.22 ± 0.02 and 0.36 ± 0.14 d^?1, respectively). At 15 °C, NAGase exhibited exponential declines in catalytic rates with age (0.79 ± 0.31 d^?1), but BGase exhibited no decline. Neither enzyme exhibited a decline in catalytic rate over 72 h at 5 °C. At 15 °C, the amount of C liberated from cellulose and chitin analogues relative to N increased, on average, by more than one order of magnitude. The ratio of C:N liberated from the two substrates remained constant across enzyme age at 25 and 5 °C, but for different reasons: no differences in decay rate across enzymes at 25 °C, and no observed decay at 5 °C. Thus, temperature-dependent decreases of catalytic activity over time may influence microbial resource allocation strategies and rates of SOM decomposition. Because the enzyme decay rates we observed differ considerably from values assumed in most models, such assumptions should be revisited when parameterizing microbial process models.     

TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic

Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.     

Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase

Pattern recognition receptors (PRRs) play a key role in plant and animal innate immunity. PRR binding of their cognate ligand triggers a signaling network and activates an immune response. Activation of PRR signaling must be controlled prior to ligand binding to prevent spurious signaling and immune activation. Flagellin perception in Arabidopsis through FLAGELLIN‐SENSITIVE 2 (FLS2) induces the activation of mitogen‐activated protein kinases (MAPKs) and immunity. However, the precise molecular mechanism that connects activated FLS2 to downstream MAPK cascades remains unknown. Here, we report the identification of a differentially phosphorylated MAP kinase kinase kinase that also interacts with FLS2. Using targeted proteomics and functional analysis, we show that MKKK7 negatively regulates flagellin‐triggered signaling and basal immunity and this requires phosphorylation of MKKK7 on specific serine residues. MKKK7 attenuates MPK6 activity and defense gene expression. Moreover, MKKK7 suppresses the reactive oxygen species burst downstream of FLS2, suggesting that MKKK7‐mediated attenuation of FLS2 signaling occurs through direct modulation of the FLS2 complex.     

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

The Qatari law, as in many other countries, uses brain death as the main criteria for organ donation and cessation of medical support. By contrast, most of the public in Qatar do not agree with the limitation or withdrawal of medical care until the time of cardiac death. The current study aims to examine the duration of somatic survival after brain death, organ donation rate in brain-dead patients as well as review the underlying etiologies and level of support provided in the state of Qatar. This is a retrospective study of all patients diagnosed with brain death over a 10-year period conducted at the largest tertiary center in Qatar (Hamad General Hospital). Among the 53 patients who were diagnosed with brain death during the study period, the median and mean somatic survivals of brain-dead patients in the current study were 3 and 4.5 days respectively. The most common etiology was intracranial hemorrhage (45.3%) followed by ischemic stroke (17%). Ischemic stroke patients had a median survival of 11 days. Organ donation was accepted by only two families (6.6%) of the 30 brain dead patients deemed suitable for organ donation. The average somatic survival of brain-dead patients is less than one week irrespective of supportive measures provided. Organ donation rate was extremely low among brain-dead patients in Qatar. Improved public education may lead to significant improvement in resource utilization as well as organ transplant donors and should be a major target area of future health care policies.     

Disorders related to sexuality and gender identity in the ICD‐11: revising the ICD‐10 classification based on current scientific evidence,best clinical practices,and human rights considerations

In the World Health Organization's forthcoming eleventh revision of the International Classification of Diseases and Related Health Problems (ICD‐11), substantial changes have been proposed to the ICD‐10 classification of mental and behavioural disorders related to sexuality and gender identity. These concern the following ICD‐10 disorder groupings: F52 Sexual dysfunctions, not caused by organic disorder or disease; F64 Gender identity disorders; F65 Disorders of sexual preference; and F66 Psychological and behavioural disorders associated with sexual development and orientation. Changes have been proposed based on advances in research and clinical practice, and major shifts in social attitudes and in relevant policies, laws, and human rights standards. This paper describes the main recommended changes, the rationale and evidence considered, and important differences from the DSM‐5. An integrated classification of sexual dysfunctions has been proposed for a new chapter on Conditions Related to Sexual Health, overcoming the mind/body separation that is inherent in ICD‐10. Gender identity disorders in ICD‐10 have been reconceptualized as Gender incongruence, and also proposed to be moved to the new chapter on sexual health. The proposed classification of Paraphilic disorders distinguishes between conditions that are relevant to public health and clinical psychopathology and those that merely reflect private behaviour. ICD‐10 categories related to sexual orientation have been recommended for deletion from the ICD‐11.     

Synthesis and Anti-HCV Activity of 4-Methoxy-7H-Pyrrolo[2,3-d] Pyrimidine Carbocyclic Nucleosides

The present study includes the exploration of new possible nucleoside mimetics based on 4-methoxy-7H-pyrrolo[2,3-d]pyrimidine carbocyclic nucleosides (4a–g), which were synthesized by 10–15 synthetic steps and characterized adequately. We report the anti-HCV activities and cytotoxicities of 4a–g. Compound 4a was analyzed by single crystal X-ray diffraction which showed some puckering in the cyclopentene ring with a 2′-endo conformation and anti-base disposition (χ = ?125.7°).