Eradication of introduced fish allows successful recovery of a stream-dwelling amphibian.
Introduction of alien fish is a major problem for the conservation of amphibians inhabiting originally fishless mountain streams. While fish eradication programs in lakes and ponds have proven successful for the recovery of amphibian populations, there is no such information for stream-dwelling amphibians, possibly because fish removal from streams is difficult and costly. Here, we show the first case of successful recovery of a stream-dwelling amphibian (Rana iberica) in a mountain area of central Spain, following eradication of introduced brook trout (Salvelinus fontinalis) and native brown trout (Salmo trutta) translocated from downstream reaches by local anglers. Electrofishing for 12 consecutive years eradicated both fish species in the introduced area, and allowed the recovery of the R. iberica population as a result of natural recolonization from nearby streams and reintroduction of captive-reared individuals. Our results demonstrate how electrofishing can be a costly but effective method for the eradication of introduced fish and the conservation of stream-dwelling amphibians.


Benign Lymphangioendothelioma - A Case Report.
Benign lymphangioendothelioma is an uncommon locally infiltrative lymphatic tumour, presenting as a slow-growing, asymptomatic, reddish-violaceous macule or plaque. Histopathologically, it is characterized by thin-walled endothelial-lined spaces that are interspersed between strands of collagen. It must be recognized and differentiated from angiosarcoma, early Kaposi's sarcoma, in view of major differences in treatment and prognosis. A 24-year-old female presented with a raised lesion over the left leg since 2 years which was associated with minimal itching. Biopsy of the lesion showed thin walled vascular channels lined by single layer of bland endothelial cells at the dermo-epidermal junction, few vessels in the dermis.


Highly sensitive automated method for DNA damage assessment: gamma-H2AX foci counting and cell cycle sorting.
Phosphorylation of the H2AX protein is an early step in the double strand break (DSB) repair pathway; therefore, phosphorylated histone (γH2AX) foci scoring is widely used as a measure for DSBs. Foci scoring is performed either manually or semi-automatically using hand-operated capturing and image analysis software. In general, both techniques are laborious and prone to artifacts associated with manual scoring. While a few fully automated methods have been described in the literature, none of them have been used to quantify γH2AX foci in combination with a cell cycle phase analysis. Adding this feature to a rapid automated γH2AX foci quantification method would reduce the scoring uncertainty that arises from the variations in the background level of the γH2AX signal throughout the cell cycle. The method was set up to measure DNA damage induced in human mammary epithelial cells by irradiation under a mammogram device. We adapted a FISH (fluorescent in situ hybridization) Spot-counting system, which has a slide loader with automatic scanning and cell capture system throughout the thickness of each cell (z-stack), to meet our assay requirements. While scanning the sample, the system classifies the selected nuclei according to the signal patterns previously described by the user. For our purposes, a double staining immunofluorescence was carried out with antibodies to detect γH2AX and pericentrin, an integral component of the centrosome. We could thus distinguish both the number of γH2AX foci per cell and the cell cycle phase. Furthermore, restrictive settings of the program classifier reduced the "touching nuclei" problem described in other image analysis software. The automated scoring was faster than and as sensitive as its manually performed counterpart. This system is a reliable tool for γH2AX radio-induced foci counting and provides essential information about the cell cycle stage. It thus offers a more complete and rapid assessment of DNA damage.


Metastatic inflammatory myofibroblastic tumor identified by EUS-FNA in mediastinal lymph nodes with ancillary FISH studies for ALK rearrangement.
Inflammatory myofibroblastic tumor (IMT) is an exquisitely rare neoplasm with a low incidence of metastasis. Previously, cytologic diagnosis of this entity, by fine needle aspiration (FNA) or endoscopic ultrasound guided fine needle aspiration (EUS-FNA), was challenging, if not impossible. However, advancements in the field of molecular pathology, the applications of which have lagged in cytopathology relative to other disciplines, now makes diagnosis possible. Here we report a case of pulmonary inflammatory myofibroblastic tumor with mediastinal nodal metastasis in a 74-year-old man, definitively diagnosed by EUS-FNA utilizing morphologic, immunohistochemical, and molecular findings, including fluorescent in situ hybridization studies for ALK gene rearrangement. This case report demonstrates the value of ancillary molecular studies to assist in the diagnosis of rare neoplasms, including those at sites of metastasis.


Patterns and time of initiation of dialysis in US children.
The purpose of this communication is to study the clinical patterns and level of residual renal function at the initiation of dialysis in children in the United States of America (US). Data were reviewed for 7,039 children under the age of 20 years and 647,600 adults extracted from the patient incidence report, obtained from the United States Renal Data Systems (USRDS), who were initiated on dialysis between January 1995 and September 2002. Based on pre-defined exclusion criteria, only 4,808 of the 7,093 (67.8%) pediatric entries were included in the analysis. About 6.9% of the entries were not used because of missing data only, 23.3% because of out of range data only, and 2.0% because of both missing and out of range data, a total of 32.2% exclusions. For adults, 570,808 (88.1%) had acceptable data. The percentage of the 4,808 children who were initiated on dialysis with an estimated GFR greater than 10 mL min(-1) per 1.73 m(2) (early start) was 49.6%. Using logistic regression, the factors affecting the probability of an early start were sex, race, type of insurance, region of the country, age at initiation of dialysis, and the year dialysis was initiated. The highest chance of starting dialysis early (0.77) was for a white male, aged 15-19 years, with insurance and residing in the Northwest part of the US The percentage of 4,808 children who initiated dialysis with an estimated GFR less than 5 mL min(-1) per 1.73 m(2) (late start) was 7.3%. The factors affecting the probability of a late start were sex, race, type of insurance, and the year dialysis was initiated. The greatest chance for a late start of dialysis was for black female patients without insurance (0.21). Mean estimated GFR at the start of dialysis was higher for children than for adults (10.7+/-4.6 vs 8.2+/-4.1 mL min(-1) per 1.73 m(2), respectively, P<0.0001). It was concluded that patterns of management of children with ESRD are not uniform among US children.


Cetacean Morbillivirus in Odontocetes Stranded along the Central California Coast, USA, 2000-15.
Effects of cetacean morbillivirus (CeMV) on dolphins vary from causing epidemics to subclinical infections. The former have been documented in the North Atlantic Ocean and Mediterranean Sea but not in the North Pacific Ocean, and the reasons for this are unknown. To explore the distribution of this virus in areas that have not experienced epidemics, we reviewed evidence for morbilliviral infection in odontocetes stranded along the California coast, US from 2000-15. Nine of 212 animals examined histologically had lesions compatible with morbilliviral infection, and 11 were tested for CeMV via reverse transcriptase-PCR. One striped dolphin ( Stenella coeruleoalba ) was PCR positive, and the sequenced product was most closely related to sequences in two strains found in cetaceans in Hawaii. This study suggests that CeMV may be a cause of morbidity and a rare contributor to mortality in cetaceans stranding along the California coast. Additional work is needed to understand CeMV distribution and host species susceptibility in this region.


Review of behavioral psychotherapy, II: sexual disorders.
Sexual dysfunction has been shown to respond to a "behavioral Masters and Johnson" approach. Several controlled studies have found this approach to be superior to other methods, with one follow-up showing improvement up to 18 months later. Good results have usually been obtained using one rather than two therapists per couple. This brings into question whether the doubling of expense by use of two therapists is justified by the marginal gains in outcome. Results of early group treatment experiments with couples with sexual dysfunction have been encouraging. Behavioral methods are also useful in reducing a variety of sexual deviations (paraphilias); recent emphasis has moved away from the patient being passively averted by the therapist toward devising his own self-management program, including self-administered aversion when necessary.


Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis.
We probed epidermal basement membranes (EBM) of acid-urea denatured skin from members of kindreds with Alport-type familial nephritis (FN) for the presence of antigens reactive with Goodpasture sera (GPS) and serum (FNS) from an Alport patient who developed anti-glomerular basement membrane (GBM) nephritis in a renal allograft. By immunoblotting, GPS reacted primarily with the 28,000 molecular weight (mol wt) monomer but also the 24,000 mol wt and 26,000 mol wt monomers of the noncollagenous globular domain (NC1) of type IV collagen from normal human GBM, while FNS identified only the 26,000-mol wt monomer. FNS reacted with EBM of 12 controls and nine unaffected male kindred members but not EBM of eight affected males. Five affected females exhibited interrupted reactivity of FNS with EBM. GPS showed variable reactivity with EBM and was not discriminating with respect to Alport-type FN. FNS did not stain renal basement members of five affected males. However, the EBM, tubular basement membrane, and Bowman's capsules of affected males contained antigens reactive with GPS. These immunochemical studies suggest that the FNS antigen is distinct from Goodpasture antigen(s). The expression of FNS antigen located on the NC1 domain of type IV collagen is altered in basement membranes of patients with Alport-type FN, and the distribution of this antigenic anomaly within kindreds suggests X-linked dominant transmission of a defective gene.


The accumulation of genetic diversity within a canopy-stored seed bank.
Many plants regenerate after fire from a canopy-stored seed bank, in which seed are housed in fire resistant confructescences (cones) that remain on maternal plants. This strategy would be favoured if plants accumulate a sufficiently large and genetically diverse seed bank during interfire intervals. We use a 16-year demographic study and surveys of microsatellite variation to quantify and explain the rate of accumulation of genetic diversity within the canopy seed bank of the shrub Banksia spinulosa. Flowering and fruit set were highly variable. An initial sample in 1991 of 354 reproductively mature plants generated 426 cones over 16 years, of which only 55 cones from 40 maternal plants persisted until 2005. By genotyping seed from these 55 cones we demonstrated that genetic diversity accumulated rapidly within the seed bank. Resampling revealed that diversity was determined by the number, not the age, of cones. Cones were widely distributed among plants, outcrossing rates were high (mean t(m) = 1.00 +/- 0.04) and biparental inbreeding low. Adults displayed little evidence of isolation by distance and the genotypic diversity of seed cohorts was independent of the density of neighbouring potential sires. We therefore estimate that within at least 13 individual years the number of cones produced per year (14-63) would have contained 100% of the adult genetic diversity. We conclude that a highly outcrossed mating system and relatively widespread pollen dispersal ensure the rapid development of a genetically diverse and spatially and temporally homogeneous seed bank.


Histone N-tails modulate sequence-specific positioning of nucleosomes.
The precise mechanisms governing sequence-dependent positioning of nucleosomes on DNA remain unknown in detail. Existing algorithms, taking into account the sequence-dependent deformability of DNA and its interactions with the histone globular domains, predict rotational setting of only 65% of human nucleosomes mapped in vivo . To uncover novel factors responsible for the nucleosome positioning, we analyzed potential involvement of the histone N-tails in this process. To this aim, we reconstituted the H2A/H4 N-tailless nucleosomes on human BRCA1 DNA (∼100 kb) and compared their positions and sequences with those of the wild-type nucleosomes. In the case of H2A tailless nucleosomes, the AT content of DNA sequences is changed locally at superhelical location (SHL) ±4, while maintaining the same rotational setting as their wild-type counterparts. Conversely, the H4 tailless nucleosomes display widespread changes of the AT content near SHL ±1 and SHL ±2, where the H4 N-tails interact with DNA. Furthermore, a substantial number of H4 tailless nucleosomes exhibit rotational setting opposite to that of the wild-type nucleosomes. Thus, our findings strongly suggest that the histone N-tails are operative in selection of nucleosome positions, which may have wide-ranging implications for epigenetic modulation of chromatin states.


Polycomb protein binding and looping mediated by Polycomb Response Elements in the ON transcriptional state.
Polycomb group proteins (PcG) mediate epigenetic silencing of important developmental genes and other targets. In Drosophila, canonical PcG-target genes contain Polycomb Response Elements (PREs) that recruit PcG protein complexes including PRC2 that tri- methylates H3K27 forming large H3K27me3 domains. In the OFF transcriptional state, PREs loop with each other and this looping strengthens silencing. Here we address the question of what PcG proteins bind to PREs when canonical PcG target genes are expressed, and whether PREs loop when these genes are ON. Our data show that the answer to this question is PRE-specific but general conclusions can be made. First, within a PcG-target gene, some regulatory DNA can remain covered with H3K27me3 and PcG proteins remain bound to PREs in these regions. Second, when PREs are within H3K27ac domains, PcG- binding decreases, however, this depends on the protein and PRE. The DNA binding protein GAF, and the PcG protein Ph remain at PREs even when other PcG proteins are greatly depleted. In the ON state, PREs can still loop with each other, but also form loops with presumptive enhancers. These data support the model that, in addition to their role in PcG silencing, PREs can act as "promoter-tethering elements" mediating interactions between promoter proximal PREs and distant enhancers.


Utility of Multi-target Nested PCR and ELISPOT Assays for the Detection of Paucibacillary Leprosy: A Possible Conclusion of Clinical Laboratory Misdiagnosis.
The diagnosis of paucibacillary (PB) leprosy often possesses a diagnostic challenge, especially for pure neuritic and lesser skin lesions with the zero bacillary load, requiring a sensitive and accurate diagnostic tool. We have included 300 clinically diagnosed new leprosy cases (comprising 98 PB cases) and analyzed the sensitivity and specificity of PB leprosy cases by nested PCR with folP, gyrA, rpoB, RLEP, and 16SrRNA and Enzyme-linked Immunospot Assay test (ELISPOT) with MMPII, NDO-BSA, and LID-1 antigens by detecting interferon gamma (IFN-γ) release. The overall positivity rates of genes tested in 300 clinical specimens were identified as 55% of 16SrRNA, 59% of RLEP, 59.3% of folP, 57.3% of rpoB, 61% of gyrA while 90% of nested folP, 92.6% of nested rpoB, and 95% of nested gyrA, and 285 (95%) of at least one gene positive cases. For PB specimens, 95% PCR positivity was achieved by three tested genes in nested PCR. The data obtained from ELISPOT for three antigens were analyzed for IFN-γ expression with 600 subjects. Among 98 PB leprosy cases, the sensitivity of MMP II, LID-1, and NDO-BSA was 90%, 87%, and 83%, respectively, and the specificity was 90%, 91%, and 86%, respectively. The total number of cases positive for at least one antigen was 90 (91.8%) in PB, which is significantly higher than that in multibacillary (MB) leprosy (56.7%). The combination of multi-targets nested PCR and ELISPOT assay provides a specific tool to early clinical laboratory diagnosis of PB leprosy cases. The two assays are complementary to each other and beneficial for screening PB patients.


Emphysema and metalloelastase expression in mouse lung induced by cigarette smoke.
Cigarette smoke (CS) causes pulmonary emphysema in humans and elastin degradation plays a key role in its pathogenesis. Previous studies on CS-exposed animals have been equivocal and have not clearly demonstrated the progression of the disease. In this study, morphometry was used to assess lung modifications to alveolar septa, airspaces, elastic and collagen fibers, and alveolar macrophages. Male (n = 40) C57/BL6 mice were exposed 3 times/day, whole body, to CS from three cigarettes for 10, 20, 30, or 60 days. Control groups (n = 10) were sham-smoked or received no exposure (day 0, n = 10). Morphometry included measurements of volume fraction of alveolar septa and airspaces, elastic and collagen fibers, and surface fraction of elastic fibers and alveolar septa. Morphometrical differences in mice after 60 days of exposure were greater than those after 10, 20, or 30 days, suggesting a progression of the disease. Inflammatory lesions in the lungs of mice contained significantly more metalloelastase (MMP-12) in macrophages at 10, 20, and 30 days than in controls of mice exposed for 60 days. These results suggest that elastin degradation took place during development of pulmonary changes in mice exposed to CS, and activation of MMPs specific for elastin may be a determining factor for susceptibility to emphysema.


The Site of Bone Marrow Acquisition Affects the Myeloid to Erythroid Ratio in Apparently Healthy Dogs.
Bone marrow (BM) cytology and histopathology are complementary tools used to investigate hematological diseases. The purpose of this study was to determine if there are site-dependent differences in the diagnostic quality, myeloid to erythroid ratio (MER), and discordant findings in samples from different sites in the same dog. Eighteen apparently healthy dogs were used in the study. The sequence of sample acquisition was randomized according to a Latin square, and samples for BM cytology and histology were collected from both humeri and both ilial crests immediately after death. Board-certified clinical and anatomical pathologists read the cytology and histology, respectively. The data were analyzed using a mixed-effect model. The site of BM acquisition did not affect BM sample quality. The rate of discordant clinical findings between sites was 0.05 (95% confidence interval, 0.01-0.13). In general, by cytology, the MERs were slightly but significantly greater in samples from the ilial crests than from the humeri ( P = .01). The measured MER for histology was nearly twice that for cytology for all sites ( P < .001). In conclusion, there was a low-rate, site-dependent discordance in diagnostic findings in BM samples and differences in MER between the ilial crest and the humerus. A similar study is justified in sick dogs with hematological disease to determine the effect of sampling site on discordant findings between sites.


A signal recognition particle receptor gene from the early-diverging eukaryote, Giardia lamblia.
The molecular mechanisms for targeting and translocation of secreted proteins are highly conserved from bacteria to mammalian cells, although the machinery is more complex in higher eukaryotes. To investigate protein transport in the early-diverging eukaryote, Giardia lamblia, we cloned the gene encoding the alpha subunit (SRalpha) of the signal recognition particle (SRP) receptor. SRalpha is a small GTPase that functions in SRP-ribosome targeting to the ER. Sequence and phylogenetic analyses showed that SRalpha from G. lamblia is most homologous to SRalpha proteins from higher eukaryotes, although it lacks some conserved motifs. Specifically, giardial SRalpha has an N-terminal extension that enables SRalpha of higher eukaryotes to interact with a beta subunit that anchors it in the ER membrane. While the C-terminal regions are similar, giardial SRalpha lacks a prominent 13 amino acid regulatory loop that is characteristic of higher eukaryotic versions. Thus, giardial SRalpha resembles that of higher eukaryotes, but likely diverged before the advent of the regulatory loop. The 1.8 kb SRalpha transcript has extremely short untranslated regions (UTRs): a 1-2 nt 5'- and a 9 nt 3' UTR with the polyadenylation signal overlapping with the stop codon. RT-PCR, Northern and Western analyses showed that SRalpha is present at relatively constant levels during vegetative growth and encystation, even though there are extensive changes in endomembrane structures and secretory activity during encystation. Imnuno-EM showed that SRalpha localizes to ER-like structures, strengthening the observation of a typical ER in G. lamlia. Unexpectedly, SRalpha was also found in the lysosome-like peripheral vacuoles, suggesting unusual protein traffic in this early eukaryote. Our results indicate that the eukaryotic type of cotranslational transport appeared early in the evolution of the eukaryotic cell.


Measuring Relationships Between Proactive Reporting State-level Prescription Drug Monitoring Programs and County-level Fatal Prescription Opioid Overdoses.
Prescription drug monitoring programs (PDMPs) that collect and distribute information on dispensed controlled substances have been adopted by nearly all US states. We know little about program characteristics that modify PDMP impact on prescription opioid (PO) overdose deaths. We measured associations between adoption of any PDMP and changes in fatal PO overdoses in 2002-2016 across 3109 counties in 49 states and D.C. We then measured changes related to the adoption of "proactive PDMPs," which report outlying prescribing/dispensing patterns and provide broader access to PDMP data by law enforcement. Comparisons were made within 3 time intervals that broadly represent the evolution of PDMPs (2002-2004, 2005-2009, and 2010-2016). We modeled overdoses using Bayesian space-time models. Adoption of electronic PDMP access was associated with 9% lower rates of fatal PO overdoses after three years (rate ratio [RR] = 0.91, 95% credible interval [CI]: 0.88-0.93) with well-supported effects for methadone (RR = 0.86,95% CI: 0.82-0.90) and other synthetic opioids (RR = 0.82, 95% CI: 0.77-0.86). Compared with states with no/weak PDMPs, proactive PDMPs were associated with fewer deaths attributed to natural/semi-synthetic opioids (2002-2004: RR = 0.72 [0.66-0.78]; 2005-2009: RR = 0.93 [0.90-0.97]; 2010-2016: 0.89 [0.86-0.92]) and methadone (2002-2004: RR = 0.77 [0.69-0.85]; 2010-2016: RR = 0.90 [0.86-0.94]). Unintended effects were observed for synthetic opioids other than methadone (2005-2009: RR = 1.29 [1.21-1.38]; 2010-2016: RR = 1.22 [1.16-1.29]). State adoption of PDMPs was associated with fewer PO deaths overall while proactive PDMPs alone were associated with fewer deaths related to natural/semisynthetic opioids and methadone, the specific targets of these programs. See video abstract at, http://links.lww.com/EDE/B619.


Mental Pain and Suicidal Tendencies in Sexual and Physical Abuse Victims.
We examine differential effects of mental pain and suicidal tendencies in female victims who have been sexually and physically abused, hypothesizing that sexual abuse victims report more mental pain and suicidal tendencies than physical abuse victims. A group of 98 women completed questionnaires that measured mental pain, suicidal tendencies and thoughts, and demographic details. Sexual abuse victims suffered more mental pain than physical abuse victims while the physical abuse victims demonstrated more repulsion by life than sexual abuse victims. Only sexual abuse victims demonstrated less attraction to life and only physical abuse victims showed more attraction to death.


Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors.
ATP analogs substituted in the gamma-phosphorus (ATPgammaS, beta, gamma-imido-ATP, and beta,gamma-methylene-ATP) were used to probe the involvement of P2 receptors in the modulation of synaptic transmission in the hippocampus, because their extracellular catabolism was virtually not detected in CA1 slices. ATP and gamma-substituted analogs were equipotent to inhibit synaptic transmission in CA1 pyramid synapses (IC50 of 17-22 microM). The inhibitory effect of ATP and gamma-phosphorus-substituted ATP analogs (30 microM) was not modified by the P2 receptor antagonist suramin (100 microM), was inhibited by 42-49% by the ecto-5'-nucleotidase inhibitor and alpha,beta-methylene ADP (100 microM), was inhibited by 74-85% by 2 U/ml adenosine deaminase (which converts adenosine into its inactive metabolite-inosine), and was nearly prevented by the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10 nM). Stronger support for the involvement of extracellular adenosine formation as a main requirement for the inhibitory effect of ATP and gamma-substituted ATP analogs was the observation that an inhibitor of adenosine uptake, dipyridamole (20 microM), potentiated by 92-124% the inhibitory effect of ATP and gamma-substituted ATP analogs (10 microM), a potentiation similar to that obtained for 10 microM adenosine (113%). Thus, the present results indicate that inhibition by extracellular ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases and channeling of the generated adenosine to adenosine A1 receptors.


Cost-Effectiveness Analysis of Pharmacist Adherence Interventions in People Living with HIV/AIDS in Pakistan.
Background: Evidence has shown the positive impact of pharmacist involvement on the adherence and health outcomes of people living with HIV/AIDS. However, whether such intervention provides value for money remains unclear. This study aims to fill this gap by assessing the cost-effectiveness of pharmacist interventions in HIV care in Pakistan. Methods: A Markov decision analytic model was constructed, considering clinical inputs, utility data, and cost data obtained from a randomized controlled trial and an HIV cohort of Pakistani origin. The analysis was conducted from a healthcare perspective, and the incremental cost-effectiveness ratio (ICER) was calculated and presented for the year 2023. Additionally, a series of sensitivity analyses were performed to assess the robustness of the results. Results: Pharmacist intervention resulted in higher quality-adjusted life years (4.05 vs. 2.93) and likewise higher annual intervention costs than usual care (1979 USD vs. 429 USD) (532,894 PKR vs. 115,518 PKR). This yielded the ICER of 1383 USD/quality-adjusted life years (QALY) (372,406 PKR/QALY), which is well below the willingness-to-pay threshold of 1658 USD (446,456 PKR/QALY) recommended by the World Health Organization Choosing Interventions that are Cost-Effective. Probabilistic sensitivity analysis reported that more than 68% of iterations were below the lower limit of threshold. Sensitivity analysis reported intervention cost is the most important parameter influencing the ICER the most. Conclusion: The study suggests that involving pharmacists in HIV care could be a cost-effective approach. These findings could help shape healthcare policies and plans, possibly making pharmacist interventions a regular part of care for people with HIV in Pakistan.


A comparative study of organized class-based exercise programs versus individual home-based exercise programs for elderly patients following hip surgery.
To evaluate and compare the effectiveness of supervised and non-supervised exercise programs for improving health and rehabilitation outcomes for elderly persons following hip surgery. Prospective, descriptive and quantitative study involving two groups: The class-based program (group A, n = 34: 21 females, 13 males, mean age 79.2 years +/- 5.23) was directed and administered in the outpatient clinic, and a home-based program (group B, n = 29, 17 females, 12 males, mean age 80.3 years +/- 5.74) which administered in the patient's home. Sixty three elderly patients began at a period of 2 weeks post hip surgery for open reduction with internal fixation. The training period took place for 14 consecutive weeks. The main outcome measures include results from physical performance test, functional reach test and short form-36 health survey questionnaire. Fifty five patients completed the exercise program. No significant difference according to gender or Body Mass Index was found between the groups. At the conclusion of 14 weeks of exercise training both groups demonstrated improvement in physical function. However, only 4 of 6 total tasks of a physical performance test were improved in the home-based group compared to improvement in all 6 tasks for the class-based group. The SF-36 scores and the functional reach test indicated that the class-based subjects also presented significant gains in contrast to no significant changes in the home exercise group. Both groups demonstrated improvement in a number of issues. However, there appears to be more positive health outcomes presented by the participants in the supervised/class-based group when compared to the non-supervised/home-based group. And therefore, patients may select to participate to either a home-based or class-based regime. The clinical relevance is the significant of the necessity for close supervision by a professional therapist. In addition, the results could have some political and economical implications on the healthcare system.


Health-Related Quality of Life (HRQOL) of Gastrointestinal Cancer Caregivers: The Impact of Caregiving
Objective: This study examined the quality of life (QOL) of caregivers for gastrointestinal (GI) cancer patients, and associated factors. Methods: A cross-sectional study was conducted at three referral hospitals in Klang Valley, Malaysia. A total of 323 pairs of patients and caregivers from the oncology units of these hospitals completed questionnaires in Malay. The QOL of caregivers was measured using The Malay Caregiver Quality of Life questionnaire. The independent variables were caregiver and patient factors, care-related factors, the Caregiver Strain Index-Malay, and the Multidimensional Scale of Perceived Social Support-Malay. Simple and multiple linear regression analyses were performed to determine the factors associated with the QOL. Variables with p < 0.05 were considered significant in the multiple analyses. Results: Female caregivers were 68.1% of the total, and 46.4% caregivers were spouses to cancer patients. Their mean age was 44.50 (13.29) years old. About 51.7% were of Malay ethnicity. The mean score for QOL was 80.17 (21.58). Being a male caregiver (beta = 5.165, p = 0.011) and of Indian ethnicity (beta = -9.163, p = 0.001) were strongly associated with caregiver QOL. Male patients contributed higher QOL scores for the caregivers compared to female patients. There was an inverse relationship among caregiving strain, duration of caregiving, and caregiver QOL. Conclusion: The identification of factors that affect QOL will allow healthcare providers to develop appropriate interventions. It is important that caregivers be in good health so as not to compromise the care they provide to their patients.


Lack of Evidence for a Role of ACE-2 Polymorphisms as a Bedside Clinical Prognostic Marker of COVID-19.
The novel SARS-CoV-2 coronavirus causes a severe respiratory syndrome referred to as coronavirus disease (COVID-19). The angiotensin-converting enzyme 2 (ACE-2) plays an important role as a cellular receptor for SARS-CoV-2 and is largely expressed in lungs, kidneys, heart and the gastrointestinal tract along with being shed in plasma. The ACE-2 gene and protein show a high level of genetic polymorphism, including simple nucleotide variation, transcriptional variation, post-transcriptional changes, and putative protein mutations that could interfere with the binding or entry of SARS-CoV-2 and affect tissue damage in lungs or other organs. Genetic polymorphisms can impact SARS-CoV-2 viral entry and COVID-19 severity. This single-center study evaluated the possible role of the main ACE-2 polymorphisms (rs143936283, rs2285666, rs41303171, rs35803318, and rs2106809) as potential prognostic markers in SARS-CoV-2-infected individuals. Frozen whole blood was used for DNA isolation and genomic DNA samples were sheared using the Covaris LE220 Focused-ultrasonicator for targeting a peak size of 410 bp. Whole-genome sequencing libraries were generated from fragmented DNA using the Illumina TruSeq DNA PCR-Free HT Library Preparation Kit and sequenced on an Illumina NovaSeq 6000. We did not identify any correlation between ACE-2 polymorphisms and COVID-19 prognosis, suggesting that the interpretation and clinical use of ACE-2 genetic polymorphisms in real-world clinical settings requires further experimental and clinical validation.


Radiotherapy and "new" drugs-new side effects?
Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments. Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity.


Dual burden of chronic physical conditions and mental disorders: Findings from the Saudi National Mental Health Survey.
Comorbidities of mental disorders and chronic physical conditions are a common medical burden reported among Western countries. National estimates of such comorbidities among the general population of Arab countries like Saudi Arabia are unknown. This study examined the prevalence of lifetime chronic physical conditions among the Saudi general population with DSM-IV 12-month mental disorders, and the associations with disability in the Kingdom of Saudi Arabia (KSA). The Saudi National Mental Health Survey, a cross-sectional household study - part of the World Mental Health (WMH) Survey Consortium - was conducted between 2013-2016 in the KSA, with 4,001 Saudi citizens aged 15-65 (response rate 61%). The World Health Organization Composite International Diagnostic Interview 3.0 was used to assess prevalence of lifetime chronic physical conditions and 12-month mental disorders; disability was measured in terms of days out of role. The prevalence of any comorbid 12-month mental disorder among those with chronic physical conditions was 24%. Major depressive disorder, social phobia, and adult separation anxiety disorder were the most common comorbid mental disorders across all chronic physical conditions. Gender, education, income, urbanicity, region, and employment were associated with the presence of any chronic physical condition. Respondents with mental / physical comorbidities had 2.97 days out of role (on average) in the last 30 days. Comorbidities of mental disorders and chronic physical conditions are common among Saudis. National efforts are needed to increase awareness of such comorbidities among the general population, and develop prevention and treatment services tailored to the needs of individuals at-risk for comorbidities.


The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns.
There is a widespread exposure of general population, including pregnant women and developing fetuses, to the endocrine disrupting chemicals (EDCs). These chemicals have been reported to be present in urine, blood serum, breast milk, and amniotic fluid. Endocrine disruptions induced by environmental toxicants have placed a heavy burden on society, since environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life-a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical, and cellular events. Humans may encounter EDCs daily and during all stages of life, from conception and fetal development through adulthood and senescence. Nevertheless, prenatal and early postnatal windows are the most critical for proper development, due to rapid changes in system growth. Although there are still gaps in our knowledge, currently available data support the urgent need for health and environmental policies aimed at protecting the public and, in particular, the developing fetus and women of reproductive age. Birth Defects Research (Part C) 108:224-242, 2016. © 2016 Wiley Periodicals, Inc.


Organizing palliative care in the rural areas of Iran: are family physician-based approaches suitable?
The provision of palliative end-of-life care (P/EOLc) for patients, wherever they live, is an increasingly important service, particularly given the increasing rates of cancer and other life-threatening diseases in Iran. However, unfortunately, those living in the rural areas of Iran are greatly disadvantaged with respect to this type of care. Therefore, the present study explored the feasibility of organizing P/EOLc in the rural areas of Iran. In this qualitative study, two focus group (FG) discussions were held in Tabriz (Iran) with rural family physicians (FPs, n=23) and key P/EOLc stakeholders (n=13). The FG sessions were recorded, transcribed, and the transcriptions checked by participants before the data were subjected to content analysis. While most FPs indicated that they did not have sufficient involvement in providing P/EOLc, they emphasized the necessity of providing P/EOLc through four main themes and 25 subthemes. The four main themes were labeled as "structures and procedures," "health care provider teams," "obstacles," and "strategies or solutions." Furthermore, according to the main themes and subthemes identified here, the key stakeholders believed that the Iranian health system and the FPs' team have the potential to provide P/EOLc services in rural areas. The most feasible strategy for providing P/EOLc in Iranian rural areas would be to use the current health care framework and base the process around the FP.


Measuring Time Use of Older Couples: Lessons from the Panel Study of Income Dynamics.
Time diaries are a well established method for providing population estimates of the amount of time and types of activities respondents carry out over the course of a full day. This paper focuses on a computer assisted telephone application developed to collect multiple, same-day 24-hour diaries from older couples who participated in the 2009 Panel Study of Income Dynamics (PSID). We present selected findings from developmental and field activities, highlighting methods for three diary enhancements: 1) implementation of a multiple, same-day diary design; 2) minimizing erroneous reporting of sequential activities as simultaneous; and 3) tailoring activity descriptors (or "follow-up" questions) that depend on a pre-coded activity value. A final section discusses limitations and implications for future time diary efforts.


Vimentin autoantibodies induce platelet activation and formation of platelet-leukocyte conjugates via platelet-activating factor.
Anti-vimentin antibodies (AVA) are associated with autoimmunity and solid organ transplantation, conditions associated with vascular disease, but their contribution to disease pathogenesis is unknown. Here, we have examined interactions between AVA (mAb and serum from patients) and various leukocyte populations using whole blood and flow cytometry. Normal blood treated with patient sera containing high AVA-IgM titers or with a vimentin-specific monoclonal IgM led to activation of platelets and other leukocytes, as demonstrated by induced expression of P-selectin, fibrinogen, tissue factor, and formation of platelet:leukocyte (P:L) conjugates and a reduction in platelet counts. This activity was antigen (vimentin)-specific and was not mediated by irrelevant IgM antibodies. Flow cytometry demonstrated that AVA do not bind directly to resting platelets in whole blood, but they bind to approximately 10% of leukocytes. Supernatant, derived from AVA-treated leukocytes, induced platelet activation, as measured by the generation of platelet microparticles, when added to platelet-rich plasma. When AVA were added to whole blood in the presence of CV-6209, a platelet-activating factor (PAF) receptor inhibitor, platelet depletion was inhibited. This suggests that PAF is one of the mediators released from AVA-activated leukocytes that leads to P:L conjugation formation and platelet activation. In summary, AVA bind to leukocytes, resulting in release of a PAF and prothrombotic factor that exert a paracrine-activating effect on platelets. Overall, this proposed mechanism may explain the pathogenesis of thrombotic events in autoimmune diseases associated with AVA.


Mapping Human Tissues with Highly Multiplexed RNA in situ Hybridization.
In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. Recently there has been a surge of multiplexed RNA in situ techniques but their application to human tissues and clinical biopsies has been limited due to their large size, general lower tissue quality and high background autofluorescence. Here we report DART-FISH, a versatile padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections at cellular resolution. We introduced an omni-cell type cytoplasmic stain, dubbed RiboSoma that substantially improves the segmentation of cell bodies. We developed a computational decoding-by-deconvolution workflow to extract gene spots even in the presence of optical crowding. Our enzyme-free isothermal decoding procedure allowed us to image 121 genes in a large section from the human neocortex in less than 10 hours, where we successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. Additionally, we demonstrated the detection of transcripts as short as 461 nucleotides, including neuropeptides and discovered new cortical layer markers. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.


Using machine learning to improve bovine tuberculosis control in herd level outbreaks.
Bovine tuberculosis (bTB), a chronic disease of cattle, is caused by the Mycobacterium bovis infection. Despite having a serious social and economic impact in the United Kingdom and Ireland, there is no antemortem gold standard diagnostic test. Tuberculin skin tests (CICT) are commonly used as a control measure with the interferon gamma (IFN-γ) assay being applied in certain circumstances. This paper utilizes data gathered describing tuberculin regression in reactors (test positive cattle) following the CICT at 72 ± 4 h post injection in herds with large bTB outbreaks. The work then applies machine learning techniques (Decision Trees, Bagging Trees and Random Forests, alongside several balancing approaches) to predict which cattle were likely to be truly infected with tuberculosis, enabling identification of atypical breakdowns that require extra investigation and providing a mechanism for quality assurance of the existing CICT bTB surveillance scheme. The analysis showed that Random Forests (RF) trained using SMOTE balancing had the joint best performance and accuracy (0.90). The importance of the two components of the interferon gamma assay within the RF model also indicated that varying the assay threshold for large outbreaks would be beneficial. Furthermore, the combined use of the RF and IFN- γ models could lead to the improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. An additional use of these models would be for quality assuring the current bTB surveillance based on CICT and post mortem inspection. Quality control is well recognized as an essential component of a disease surveillance/eradication programme.Clinical Relevance- Bovine tuberculosis remains a disease that is hard to control on a national level. The use of the machine learning model could lead to significant improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. Advanced modelling, such as this, has the potential to strengthen the efficacy of disease surveillance and the eradication strategy and can meaningfully contribute to animal disease national control plans.


Motor Cortex Causally Contributes to Vocabulary Translation following Sensorimotor-Enriched Training.
The role of the motor cortex in perceptual and cognitive functions is highly controversial. Here, we investigated the hypothesis that the motor cortex can be instrumental for translating foreign language vocabulary. Human participants of both sexes were trained on foreign language (L2) words and their native language translations over 4 consecutive days. L2 words were accompanied by complementary gestures (sensorimotor enrichment) or pictures (sensory enrichment). Following training, participants translated the auditorily presented L2 words that they had learned. During translation, repetitive transcranial magnetic stimulation was applied bilaterally to a site within the primary motor cortex (Brodmann area 4) located in the vicinity of the arm functional compartment. Responses within the stimulated motor region have previously been found to correlate with behavioral benefits of sensorimotor-enriched L2 vocabulary learning. Compared to sham stimulation, effective perturbation by repetitive transcranial magnetic stimulation slowed down the translation of sensorimotor-enriched L2 words, but not sensory-enriched L2 words. This finding suggests that sensorimotor-enriched training induced changes in L2 representations within the motor cortex, which in turn facilitated the translation of L2 words. The motor cortex may play a causal role in precipitating sensorimotor-based learning benefits, and may directly aid in remembering the native language translations of foreign language words following sensorimotor-enriched training. These findings support multisensory theories of learning while challenging reactivation-based theories.SIGNIFICANCE STATEMENT Despite the potential for sensorimotor enrichment to serve as a powerful tool for learning in many domains, its underlying brain mechanisms remain largely unexplored. Using transcranial magnetic stimulation and a foreign language (L2) learning paradigm, we found that sensorimotor-enriched training can induce changes in L2 representations within the motor cortex, which in turn causally facilitate the translation of L2 words. The translation of recently acquired L2 words may therefore rely not only on auditory information stored in memory or on modality-independent L2 representations, but also on the sensorimotor context in which the words have been experienced.


Innate Immunity Protein Tag7 Induces 3 Distinct Populations of Cytotoxic Cells That Use Different Mechanisms to Exhibit Their Antitumor Activity on Human Leukocyte Antigen-Deficient Cancer Cells.
The search for new immune response mechanisms capable of controlling immune-evasive tumor cells devoid of the MHC antigen is a challenging task for immunologists. In this study, we found that the treatment of human peripheral blood lymphocytes with the innate immunity protein Tag7 (PGRP-S, PGLYRP1) induces differentiation of the populations of NK (natural killer) cells and CD8+ and CD4+ T lymphocytes that are cytotoxic for human leukocyte antigen-negative tumor cells. These populations employ different mechanisms of tumor cell lysis (based on the release of granzymes in the case of NK cells and on the FasL-Fas interaction in the case of CD8+ and CD4+ T lymphocytes) and induce different death pathways (apoptosis or necroptosis) in tumor cells. An analysis of genes activated in leukocyte populations after Tag7 treatment and experiments with specific inhibitors have shown that the TREM-1 receptor expressed on the monocyte cell surface is essential for activation of cytotoxic activity. Overall, the results of this study provide evidence for a novel role of the Tag7 protein in the immune response.


Species- and organ-specificity of secretory proteins derived from human prostate and seminal vesicles.
Polyclonal antibodies against semenogelin (SG) isolated from human seminal vesicle secretion and acid phosphatase (PAP), beta-microseminoprotein (beta-MSP), and Prostate-Specific Antigen (PSA) derived from human prostatic fluid, as well as a monoclonal antibody against beta-MSP were used for immunocytochemical detection of the respective antigens in different organs from different species. SG immunoreactivity was detected in the epithelium of the pubertal and adult human and in monkey seminal vesicle, ampulla of the vas deferens, and ejaculatory duct. PAP, beta-MSP, and PSA immunoreactivities were detected in the pubertal and adult human prostate and the cranial and caudal monkey prostate. With the exception of a weak PSA immunoreactivity in the proximal portions of the ejaculatory duct, none of the latter antisera reacted with seminal vesicle, ampullary, and ejaculatory duct epithelium. Among the non-primate species studied (dog, bull, rat, guinea pig) only the canine prostatic epithelium displayed a definite immunoreactivity with the PAP antibody and a moderate reaction with the PSA antibody. No immunoreaction was seen in bull and rat seminal vesicle and canine ampulla of the vas deferens with the SG antibody. The same was true for the (ventral) prostate of rat, bull, and dog for beta-MSP. The epithelium of the rat dorsal prostate showed a slight cross-reactivity with the monoclonal antibody against beta-MSP and one polyclonal antibody against PSA. The findings indicate a rather strict species-dependent expression of human seminal proteins which show some similarities in primates, but only marginal relationship to species with different physiology of seminal fluid.


Two-level delivery systems for oral administration of peptides and proteins based on spore capsules of Lycopodium clavatum.
Two-level delivery systems (DSs) for oral administration of therapeutic proteins and peptides were developed. The first level consists of outer walls of Lycopodium clavatum spores (sporopollenin exine capsules, SECs) with included target objects; the alginate microgranules serve as the second (outer) level. Alginate (a pH-dependent natural polymer) protects peptides from gastric acidity and enzyme exposure and provides slow release of target objects in an alkaline intestinal medium. Introducing ovomucoid (a peptidase inhibitor) into alginate coatings prevents enzymatic hydrolysis of peptide objects in the intestinal medium. The elemental composition of spores and SECs was controlled using energy-dispersion spectroscopy and combustion analysis; their morphology was visualized by SEM. The efficiencies of different methods of SEC loading were compared. It was demonstrated that the load value was controlled by molecular mass and the value of the isoelectric point of target objects. A comparison of peptide in vitro release profiles from DSs of various structures into simulated gastric and intestinal fluids was carried out. The mechanism of peptide release from two-level DSs was suggested. SECs were found in rat blood after intragastric administration of the two-level DSs. Time profiles of therapeutic peptide release were obtained in vivo.


Presence and integration of human papillomavirus type 6 in a tonsillar carcinoma.
Human papillomavirus type 6 subtype a (HPV-6a) was detected in a human invasive tonsillar carcinoma. Southern blot hybridization analysis showed the presence of additional bands when using non-cutting and single-cut restriction enzymes. Molecular cloning yielded two recombinant clones of 8.0 and 1.4 kb in size. The first represents the complete HPV-6a genome. Sequence analysis of the second clone showed a 0.6 kb DNA sequence corresponding to the L2 region of HPV-6a, whereas the rest belongs to cellular sequences. These data show the presence of a usually low risk HPV type in an invasive carcinoma, at an unusual infection site, with viral DNA integrated into the host genome. These findings add evidence in support of the hypothesis of a relationship between HPV infection and at least some ororespiratory cancers.


Analysis of water and NaCl solution acceptance by schedule-induced polydipsia.
Animals were trained on a VI 1-min schedule for food pellets, and concurrent water intake was measured. The polydipsia induced was analyzed in terms of the frequency distribution of post-pellet licking burst sizes and the trend of polydipsia throughout the session. An ascending series of NaCl solutions was presented consecutively over daily sessions and a typical NaCl acceptance-rejection intake function was generated. Beginning in the 0.9-1.2% NaCl range, the animals drank less often during the session but took larger drinks when they did drink. Neither the frequency of drinks nor the mean licking burst size were simply related to the volumes of NaCl solution consumed. The NaCl acceptance-rejection function cannot be explained in terms of water repletion factors alone.


Relaxation dynamics of tryptophan in water: A UV fluorescence up-conversion and molecular dynamics study.
We report on an ultrafast experimental and simulations study of the early relaxation events of photoexcited tryptophan in water. Experimentally, we used fluorescence up-conversion in both polychromatic and single wavelength detection modes in the 300-480 nm range with polarization dependence. We report on the time evolution of the Stokes shift, bandwidth, and anisotropy from tens of femtoseconds to picoseconds. These observables contain signatures of the simultaneous occurrence of intramolecular and solvent-molecule interactions, which we disentangle with the help of nonequilibrium molecular dynamics simulations. We also observe a breakdown of the linear response approximation to describe our results.


Reversible cross-tolerance to platelet-activating factor signaling by bacterial toxins.
Bacterial toxins signaling through Toll-like receptors (TLRs) are implicated in the pathogenesis of many inflammatory diseases. Among the toxins, lipopolysaccharide (LPS) exerts its action via TLR-4 while lipoteichoic acid (LTA) and bacterial lipoproteins such as Braun lipoprotein (BLP) or its synthetic analogue Pam3CSK4 act through TLR-2. Part of the TLR mediated pathogenicity is believed to stem from endogenously biosynthesized platelet-activating factor (PAF)- a potent inflammatory phospholipid acting through PAF-receptor (PAF-R). However, the role of PAF in inflammatory diseases like endotoxemia is controversial. In order to test the direct contribution of PAF in TLR-mediated pathogenicity, we intraperitoneally injected PAF to Wistar albino mice in the presence or absence of bacterial toxins. Intraperitoneal injection of PAF (5 μg/mouse) causes sudden death of mice, that can be delayed by simultaneously or pre-treating the animals with high doses of bacterial toxins- a phenomenon known as endotoxin cross-tolerance. The bacterial toxins- induced tolerance to PAF can be reversed by increasing the concentration of PAF suggesting the reversibility of cross-tolerance. We did similar experiments using human platelets that express both canonical PAF-R and TLRs. Although bacterial toxins did not induce human platelet aggregation, they inhibited PAF-induced platelet aggregation in a reversible manner. Using rabbit platelets that are ultrasensitive to PAF, we found bacterial toxins (LPS and LTA) and Pam3CSK4 causing rabbit platelet aggregation via PAF-R dependent way. The physical interaction of PAF-R and bacterial toxins is also demonstrated in a human epidermal cell line having stable PAF-R expression. Thus, we suggest the possibility of direct physical interaction of bacterial toxins with PAF-R leading to cross-tolerance.


[Formation of the vascular-receptor connections in the human forearm muscles].
The data on formation and construction principles of the blood supply system in the terminal sensitive apparatuses of the human forearm muscles during embryogenesis and early postnatal period are presented. During the intrauterine development, the formation of the vascular-receptor relations takes place in the sequence corresponding to the anlage of the receptors. The first blood vessels appear in the area of the nonencapsulated sensitive terminals and only after in the encapsulated receptors. The latter have their own blood supply system which is formed by the vessels of the intramuscular neural fasciculi and the surrounding muscular tissue. Around the sensitive terminals thick microvascular networks are formed, they often tightly adhere the external receptor capsule. The intrareceptor capillaries are situated in the mass of the neural terminals and sometimes form capillary loops in them.


Teaching pharmacy history: the antipodean experience.
This paper, co-authored by Dr. Rosemary Beresford, the Associate Dean of Undergraduate Programmes in the School of Pharmacy at the University of Otago, in New Zealand was presented by Mr Geoffrey Miller to the 75th Anniversary Congress of the International Society for the History of Pharmacy, held in Lucern Switzerland in September 2001.


Outcome measures and methods of assessment of soft tissue augmentation interventions in the context of dental implant therapy: A systematic review of clinical studies published in the last 10 years.
To identify and report outcome measures and methods of assessment on soft tissue augmentation interventions in the context of dental implant therapy reported in clinical studies published in the last 10 years. The protocol of this Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review was registered in PROSPERO (CRD42021252214). A literature search was conducted to identify articles that met the pre-established eligibility criteria. Data of interest, with an emphasis on outcome measures, were extracted. For each outcome, specific methods and timing of assessment were described in detail. Following a critical qualitative analysis of the data, outcome measures were categorized. Primary outcomes were identified, and the frequency of reporting in the selected articles was calculated. Additionally, risk-of-bias assessments were performed for individual articles and primary outcomes. Ninety-two articles, of which 39 reported randomized controlled trials (RCTs), 20 non-RCTs, and 33 case series studies, were selected. Outcome measures were categorized into either investigator-evaluated outcome measures (i.e., clinical, digital imaging, aesthetic, histological, biomarker, and safety) or patient-reported outcome measures (PROMs). Clinical outcomes were the most frequently reported type of outcome. Considering all categories, the most frequently reported primary outcomes were facial mucosa thickness assessed with clinical methods (22.83%), facial keratinized mucosa width assessed with clinical methods (19.57%), facial mucosal margin position/recession assessed with clinical methods (18.48%), facial mucosa thickness assessed with digital imaging methods (11.96%), facial soft tissue volume assessed with digital imaging methods (9.78%), and supracrestal tissue height assessed with clinical methods (9.78%). No distinguishable patterns of association between specific types or quality (level of bias) of clinical studies and the choice of primary outcomes were observed. Clinical research on peri-implant soft tissue augmentation has progressively increased in the last 10 years. Although clinical outcome measures were the most frequently reported outcomes in the selected literature, trends in the field are indicative of a shift from traditional clinical assessment methods to the use of digital technologies. PROMs were generally under-reported but should be considered an integral methodological component in future clinical studies.


The BACTEC TB system in the laboratory diagnosis of mycobacterial infection.
to compare the BACTEC TB system with our conventional multimedia system for the isolation of mycobacteria from clinical specimens. specimens received over a two year period were cultured into BACTEC 12B vials and onto a variety of solid and liquid media routinely used by us for the isolation of mycobacteria. Cultures were observed regularly for bacterial growth, and examined for the presence of mycobacteria by acid fast microscopy. All results were recorded. At the end of the two year period the results for the two methods were compared. of the 4443 specimens cultured by both methods, 260 were positive for mycobacteria. Sensitivity and specificity were 88.31% and 99.35% respectively for the BACTEC, and 84.41% and 99.96% respectively for our routine multimedia system. Tuberculosis was confirmed by the BACTEC TB system in six patients who were otherwise culture negative. One of these patients had tuberculous meningitis. Three patients culture positive for M tuberculosis by our routine method, were negative by the BACTEC. Twenty-nine false positive cultures were detected, 27 by the BACTEC TB system alone. the BACTEC TB system is a rapid and sensitive system for the detection of mycobacteria in clinical specimens, and has proved to be a useful adjunct to our routine multimedia system. However, decreased specificity, particularly with lower respiratory tract specimens, means that positive results from these sites can be reported less confidently when they are detected by the BACTEC TB system alone. This negates some of the advantages of the BACTEC TB system for the detection of mycobacterial disease of the lungs.


Revisiting miRNA Association with Melanoma Recurrence and Metastasis from a Machine Learning Point of View.
The diagnostic and prognostic value of miRNAs in cutaneous melanoma (CM) has been broadly studied and supported by advanced bioinformatics tools. From early studies using miRNA arrays with several limitations, to the recent NGS-derived miRNA expression profiles, an accurate diagnostic panel of a comprehensive pre-specified set of miRNAs that could aid timely identification of specific cancer stages is still elusive, mainly because of the heterogeneity of the approaches and the samples. Herein, we summarize the existing studies that report several miRNAs as important diagnostic and prognostic biomarkers in CM. Using publicly available NGS data, we analyzed the correlation of specific miRNA expression profiles with the expression signatures of known gene targets. Combining network analytics with machine learning, we developed specific non-linear classification models that could successfully predict CM recurrence and metastasis, based on two newly identified miRNA signatures. Subsequent unbiased analyses and independent test sets (i.e., a dataset not used for training, as a validation cohort) using our prediction models resulted in 73.85% and 82.09% accuracy in predicting CM recurrence and metastasis, respectively. Overall, our approach combines detailed analysis of miRNA profiles with heuristic optimization and machine learning, which facilitates dimensionality reduction and optimization of the prediction models. Our approach provides an improved prediction strategy that could serve as an auxiliary tool towards precision treatment.


SUPERIOR SVG: no touch saphenous harvesting to improve patency following coronary bypass grafting (a multi-Centre randomized control trial, NCT01047449).
Single centre studies support No Touch (NT) saphenous vein graft (SVG) harvesting technique. The primary objective of the SUPERIOR SVG study was to determine whether NT versus conventional (CON) SVG harvesting was associated with improved SVG patency 1 year after coronary artery bypass grafting surgery (CABG). Adults undergoing isolated CABG with at least 1 SVG were eligible. CT angiography was performed 1-year post CABG. Leg adverse events were assessed with a questionnaire. A systematic review was performed for published NT graft patency studies and results aggregated including the SUPERIOR study results. Two hundred and-fifty patients were randomized across 12-centres (NT 127 versus CON 123 patients). The primary outcome (study SVG occlusion or cardiovascular (CV) death) was not significantly different in NT versus CON (NT: 7/127 (5.5%), CON 13/123 (10.6%), p = 0.15). Similarly, the proportion of study SVGs with significant stenosis or total occlusion was not significantly different between groups (NT: 8/102 (7.8%), CON: 16/107 (15.0%), p = 0.11). Vein harvest site infection was more common in the NT patients 1 month postoperatively (23.3% vs 9.5%, p < 0.01). Including this study's results, in a meta-analysis, NT was associated with a significant reduction in SVG occlusion, Odds Ratio 0.49, 95% Confidence Interval 0.29-0.82, p = 0.007 in 3 randomized and 1 observational study at 1 year postoperatively. The NT technique was not associated with improved patency of SVGs at 1-year following CABG while early vein harvest infection was increased. The aggregated data is supportive of an important reduction of SVG occlusion at 1 year with NT harvesting. NCT01047449 .


Famine as agricultural catastrophe: the crisis of 1622-4 in east Lancashire.
This article argues that historians have paid insufficient attention to the agrarian roots of early modern English famines. While not dismissing the insights arising from entitlements theory, the article takes issue with recent writings that have explained the famine of 1622–3 in north-west England as an entitlements crisis. It offers new empirical evidence from an estate in east Lancashire to demonstrate the scale of the crisis in the early 1620s, using estate accounts to produce new price data and estimates of productivity. On the basis of oat tithe data, the scale of the shortfall in foodstuffs in the harvest of 1621 is demonstrated as being probably in the region of a third; that of the following year has to be inferred from price data. The evidence shows that the crisis was not limited to the arable economy, but was followed by an extensive restocking of the pastoral economy. The article therefore makes a contribution to the growing interest in weather as an exogenous factor.


The reaction of nitrite with the haemocyanin of the Roman snail (Helix pomatia).
The reaction of nitrite at pH 5.0-7.0 with the deoxyhaemocyanin of a mollusc, the Roman snail (Helix pomatia), yielded nitrosylhaemocyanin (CuIA.NO+ CuIIB), in contrast with the formation of methaemocyanin with the deoxyhaemocyanin of the crustacean Astacus leptodactylus (mud crayfish). With Helix haemocyanin 1 NO was thereby liberated per active site, as shown by m.s., as against 2 NO with Astacus haemocyanin. Helix nitrosylhaemocyanin was characterized in c.d. by the negative extremum at 336 nm (CuIA.NO+) and by the mononuclear e.p.r. signal at g = 2 (CuIIB). Binuclear e.p.r. signals have been observed after the addition of nitrite to methaemocyanins. With Astacus methaemocyanin, no further reaction occurred, whereas with Helix methaemocyanin the mononuclear e.p.r. signal, characteristic for nitrosylhaemocyanin gradually appeared. This formation of Helix nitrosylhaemocyanin implicates the binding, most likely on CuIIA, of a second nitrite besides a bridging nitrite, so that a dismutation into NO and NO2 can occur there. A further dismutation of NO2 yields nitrite and nitrate. The formation of the latter was demonstrated by Raman spectrometry. The reaction rate of Helix methaemocyanin with nitrite decreased with increasing pH according to the Henderson-Hasselbalch equation with a pKa value of 6.77, attributed to a mu-aquo bridging ligand, which can be exchanged for nitrite, in equilibrium with a mu-hydroxo ligand which cannot. These data also favour the formulation of the final reaction product as nitrosylhaemocyanin instead of semi-methaemocyanin, with or without bound nitrite.


[Depression and medical illness].
There are medical diseases that associate a depressive syndrome in their evolution, which can on occasions precede the somatic symptoms. This article offers a description of the importance of depressive syndromes in the care of a patient with medical pathology. After analysing the mode of presentation of the depressive symptomology in medical patients, as well as the different diagnostic keys that make it possible to avoid mistaken or incomplete diagnoses, it deals with the relationship between depressive symptoms and numerous pathologies. Finally, it reviews those psychiatric disorders that frequently associate unspecific medical symptoms with depressive anxiety syndrome, which end up complicating the handling of these patients. The article does not aim to analyse those depressive pictures that are reactive to the difficulties of some patients in assuming their role as patients with an illness, or the limitations that certain disorders, treatments or prognoses might entail.


Characterization of the soybean GmALMT family genes and the function of GmALMT5 in response to phosphate starvation.
A potential mechanism to enhance utilization of sparingly soluble forms of phosphorus (P) is the root secretion of malate, which is mainly mediated by the ALMT gene family in plants. In this study, a total of 34 GmALMT genes were identified in the soybean genome. Expression patterns diverged considerably among GmALMTs in response to phosphate (Pi) starvation in leaves, roots and flowers, with expression altered by P availability in 26 of the 34 GmALMTs. One root-specific GmALMT whose expression was significantly enhanced by Pi-starvation, GmALMT5, was studied in more detail to determine its possible role in soybean P nutrition. Analysis of GmALMT5 tissue expression patterns, subcellular localization, and malate exudation from transgenic soybean hairy roots overexpressing GmALMT5, demonstrated that GmALMT5 is a plasma membrane protein that mediates malate efflux from roots. Furthermore, both growth and P content of transgenic Arabidopsis overexpressing GmALMT5 were significantly increased when sparingly soluble Ca-P was used as the external P source. Taken together, these results indicate that members of the soybean GmALMT gene family exhibit diverse responses to Pi starvation. One member of this family, GmALMT5, might contribute to soybean P efficiency by enhancing utilization of sparingly soluble P sources under P limited conditions.


Thrombocytopenia in Patients with Systemic Lupus Erythematosus.
Thrombocytopenia can be one of the first manifestations of systemic lupus erythematosus and occurs in up to 40% of patients. Additionally, approximately 2% of patients with primary immune thrombocytopenia may develop systemic lupus erythematosus. Systemic lupus erythematosus is a highly heterogeneous disease, and in some patients, it may present mainly with hematological findings. Thrombocytopenia associated with systemic lupus erythematosus is also diverse, ranging from asymptomatic to severe, acute, or chronic cases. Several studies suggest that the coexistence of immune thrombocytopenia and systemic lupus erythematosus may be linked to a shared genetic background among various autoimmune diseases. Studies have reported correlations between thrombocytopenia and increased disease activity as well as kidney and central nervous system involvement in systemic lupus erythematosus. Severe thrombocytopenia is considered a poor prognostic factor in systemic lupus erythematosus. Despite this knowledge, the exact cause of reduced platelet count in systemic lupus erythematosus remains relatively unknown. Mainly, an excess of platelet destruction and/or reduced production from megakaryocytes are considered the primary factors contributing to systemic lupus erythematosus-associated thrombocytopenia. Given the prognostic significance of thrombocytopenia, there is a possibility of a pathogenic mechanistic role of thrombocytopenia and platelets in systemic lupus erythematosus. In systemic lupus erythematosus, platelets are activated and play a role in promoting autoimmune and inflammatory responses by interacting with both the innate and adaptive immunity. There is no randomized clinical trial in the treatment of systemic lupus erythematosus-related thrombocytopenia. Treatment approach of thrombocytopenia in lupus is almost similar to the treatment of immune thrombocytopenia. Considering the role of platelets in both inflammation and tissue injury, platelet activation and platelet-immune cell interaction might be important therapeutic strategies in the treatment of systemic lupus erythematosus.


Smoking-induced change in intrasynaptic dopamine concentration: effect of treatment for Tobacco Dependence.
The aim of this study was to determine whether standard treatments for Tobacco Dependence affect smoking-induced changes in intrasynaptic dopamine (DA) concentration. Forty-three otherwise healthy adult cigarette smokers (10 to 40 cigarettes per day) were treated with either practical group counseling (PGC) psychotherapy (n=14), bupropion HCl (n=14), or matching pill placebo (n=15) (random assignment) for 8 weeks. Before and after treatment, each subject underwent a bolus-plus-continuous-infusion (11)C-raclopride positron emission tomography (PET) scanning session, during which he or she smoked a regular cigarette. The PET scanning outcome measure of interest was percent change in smoking-induced (11)C-raclopride binding potential (BP(ND)) in the ventral caudate/nucleus accumbens (VCD/NAc), as an indirect measure of DA release. Although the entire study sample had a smaller mean smoking-induced reduction in VCD/NAc BP(ND) after treatment (compared to before treatment), this change was highly correlated with smaller total cigarette puff volumes (and not other treatment variables). These data indicate that smoking-induced DA release is dose-dependent, and is not significantly affected by reductions in daily smoking levels or treatment type.


Assessing whether ad hoc clinician-generated patient questionnaires provide psychometrically valid information.
The provision of psychometrically valid patient reported outcomes (PROs) improves patient outcomes and reflects their quality of life. Consequently, ad hoc clinician-generated questionnaires of the past are being replaced by more rigorous instruments. This change, while beneficial, risks the loss/orphaning of decades-long information on difficult to capture/chronically ill populations. The goal of this study was to assess to the quality of data retrieved from these legacy questionnaires. Participants included 8563 patients who generated a total of 12,626 hospital admissions over the 2004-2014 study period. Items used to screen for issues related to function, mood, symptoms, and social support among patients with chronic disease were identified in our medical center's patient information questionnaire. Cluster and exploratory factor analyses (EFA) followed by multidimensional item response theory (MIRT) analyses were used to select items that defined factors. Scores were derived with summation and MIRT approaches; inter-factor relationships and relationships of factor scores to assigned diagnostic codes were assessed. Rasch analyses assessed the constructs' measurement properties. Literature review and clinician interviews yielded four hypothesized constructs: psychological distress/wellbeing, symptom burden, social support, and physical function. Rasch analyses showed that, while all had good measurement properties, only one, function, separated individuals well. In exploratory factor analyses (EFA), 11 factors representing depression, respiratory symptoms, musculoskeletal pain, family support, mobility, activities of daily living, alcohol consumption, weight loss, fatigue, neurological disorders, and fear at home were identified. Based on the agreement between EFA and cluster analyses as well as Cronbach's alpha, six domains were retained for analyses. Correlations were strong between activities of daily living and mobility (.84), and moderate between pain and mobility (.37) and psychological distress (.59) Known-group validity was supported from the relationships between factor scores and the relevant diagnostic code assignments (.12 to .20). Items from ad hoc clinician-generated patient information questionnaires can be aggregated into valid factors that assess supportive care domains among chronically ill patients. However, the binary response options offered by many screening items limit their information content and consequently, as highlighted by Rasch analyses, their ability to meaningfully discriminate trait levels in these populations.


Sex Chromosome Turnover in Moths of the Diverse Superfamily Gelechioidea.
Sex chromosomes play a central role in genetics of speciation and their turnover was suggested to promote divergence. In vertebrates, sex chromosome-autosome fusions resulting in neo-sex chromosomes occur frequently in male heterogametic taxa (XX/XY), but are rare in groups with female heterogamety (WZ/ZZ). We examined sex chromosomes of seven pests of the diverse lepidopteran superfamily Gelechioidea and confirmed the presence of neo-sex chromosomes in their karyotypes. Two synteny blocks, which correspond to autosomes 7 (LG7) and 27 (LG27) in the ancestral lepidopteran karyotype exemplified by the linkage map of Biston betularia (Geometridae), were identified as sex-linked in the tomato leafminer, Tuta absoluta (Gelechiidae). Testing for sex-linkage performed in other species revealed that while LG7 fused to sex chromosomes in a common ancestor of all Gelechioidea, the second fusion between the resulting neo-sex chromosome and the other autosome is confined to the tribe Gnoreschemini (Gelechiinae). Our data accentuate an emerging pattern of high incidence of neo-sex chromosomes in Lepidoptera, the largest clade with WZ/ZZ sex chromosome system, which suggest that the paucity of neo-sex chromosomes is not an intrinsic feature of female heterogamety. Furthermore, LG7 contains one of the major clusters of UDP-glucosyltransferases, which are involved in the detoxification of plant secondary metabolites. Sex chromosome evolution in Gelechioidea thus supports an earlier hypothesis postulating that lepidopteran sex chromosome-autosome fusions can be driven by selection for association of Z-linked preference or host-independent isolation genes with larval performance and thus can contribute to ecological specialization and speciation of moths.


Chondrogenic Differentiation of Pluripotent Stem Cells under Controllable Serum-Free Conditions.
The repair of damaged articular cartilage using currently available implantation techniques is not sufficient for the full recovery of patients. Pluripotent stem cells (iPSC)-based therapies could bring new perspectives in the treatment of joint diseases. A number of protocols of in vitro differentiation of iPSC in chondrocytes for regenerative purposes have been recently described. However, in order to use these cells in clinics, the elimination of animal serum and feeder cells is essential. In our study, a strictly defined and controllable protocol was designed for the differentiation of pluripotent stem cells (BG01V, ND 41658*H, GPCCi001-A) in chondrocyte-like cells in serum- and a feeder cell-free system, using the embryoid bodies step. The extension of the protocol and culture conditions (monolayer versus 3D culture) was also tested after the initial 21 days of chondrogenic differentiation. Promotion of the chondrogenic differentiation in 3D culture via the elevated expression of genes related to chondrogenesis was achieved. Using immunofluorescence and immunohistochemistry staining techniques, the increased deposition of the specific extracellular matrix was indicated. As a result, chondrocyte-like cells in the early stages of their differentiation using pellet culture under fully controlled and defined conditions were obtained.


Multimode-interference-effect-based all-fiber displacement sensing system for an orthopedic Ilizarov apparatus device.
The paper describes a multimode-interference-effect-based single-mode-multimode-single-mode (SMS) fiber optic sensing system for wide-range displacement monitoring on an Ilizarov orthopedic external fixation device. Displacement measurement is implemented as the uniform extension of a spring, which is connected to an SMS optical fiber displacement sensor, allowing full displacement characterization. SMS fiber structures are used together with a macrobending-fiber-based interrogation system to measure temperature perturbation and hence eliminate its effect on the displacement measurement. Transmission spectra are measured, achieving a displacement measurement range of 110 mm with maximum sensitivity of -53 pm/mm and a resolution of 500 μm. The all-fiber sensing system has facilitated a clinical device with a wide displacement range operating in real-time when attached to the Ilizarov apparatus.


Automatic Breathing Pattern Analysis from Reading-Speech Signals.
As the speech production mechanism is related to the breathing process, speech signals and breathing patterns impact each other. Breathing patterns are the physiological signals which help in understanding the psychological, physiological and cognitive states of an individual. Capturing such patterns relies on the availability of equipment such as respiratory belts, which are costly and uncomfortable to wear for long duration. In this paper, we attempt to extract the breathing patterns from speech signals, which are easily available and can be recorded using a smartphone's microphone. In the presented work, simultaneous speech and breath signals are captured from 100 Indians of the age group 20 to 25 years while they read a phonetically balanced passage in English language. We have identified five distinct breathing templates; following two broad speech-breath categories, exhibited by the speakers while they read the same passage. For one of the two categories, the time domain features with regression network can extract the breathing patterns from speech with a Pearson correlation coefficient of 0.70. By computational modelling, we distinguish these two breathing categories from speech with a classification accuracy of 79%.


Urinary biomarkers of prenatal atrazine exposure and adverse birth outcomes in the PELAGIE birth cohort.
Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies--and fewer epidemiologic investigations--have examined the potential effects of prenatal exposure. We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor). This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation. We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0-2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0-2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor. This study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use.


Topical L-Ascorbic Acid Formulation for a Better Management of Non-Melanoma Skin Cancer: Perspective for Treatment Strategies.
L-ascorbic acid, is a well-known molecule, sometimes used as antioxidant for skin care. Nonetheless, few studies have taken in account its utility as topical treatment for non-melanoma skin vancer. Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma and is widespread worldwide with an increasing incidence. The purpose of this paper is to analyze the characteristics of L-ascorbic acid topical formulation, its percutaneous absorption and biochemical mechanism, focusing on its anti-cancer properties. In particular, it will be described how the pH and the concentration of the formulation are able to influence its distribution in the skin and tissues. We will report, the current knowledge on the pharmacokinetic aspects of L-ascorbic acid that allows us to reconsider it in the light of its ability to act as a prodrug and as an anticancer agent. Lastly, a short review with the aim to find any evidence of a possible clinical use of L-ascorbic acid for the treatment of non-melanoma skin cancer was made.


Sexuality in women with traumatic spinal cord injury.
Sexuality in spinal cord injured women has largely been neglected. One reason may be the male dominance amongst traumatically spinal cord injured individuals. The purpose of this study is to elucidate sexual issues in women with spinal cord injuries. Survey of near-total prevalence population in the greater Stockholm area. Structured interview, based on a standardized questionnaire. Self-rating scales for evaluation of the importance of sexual activity before and after injury and for defining and rating the medical problem most significantly interfering with sexual activity. Marital status and/or partnership pre- and post-injury and information on sexual matters provided after injury were evaluated in detail. Out of a total 65 women, 62 participated in the study. Women with complete and incomplete cervical lesions rated the importance of sexual activity significantly lower after, as compared to before, spinal cord injury. No significant differences were found in women with lower-level lesions. Urinary leakage, spasticity and positioning problems were the medical problems most significantly interfering with partner-related sexual activity. Only six women had received information on sexual matters before discharge from hospital. None of the partners had received such information. The women's neurological status affect their ability to adapt sexually after injury. Medical problems commonly interfere with sexuality and should be identified and treated. No adverse impact of spinal cord injury on marital status could be confirmed. Sexual counseling has yet to become an integral part of rehabilitation.


[Ultrasonically controlled percutaneous high frequency thermotherapy of liver tumors with perfused needle electrodes].
Percutaneous radiofrequency ablation (HFTT) is a new therapeutic technique for the treatment of inoperable primary and secondary liver tumors. We report our initial experience using a newly developed perfusion electrode. Twelve liver tumors (11 metastases of colorectal tumors, 1 hepatocellular carcinoma) were treated in 5 inoperable patients. The patients had 1 to 3 liver tumors. All lesions were cytologically confirmed and measured 12-47 mm. The technique was approved by the institutional review board and informed consent was obtained from all patients. A 12-mm-needle electrode with a 15-mm-active tip was introduced into the liver tumors under ultrasound guidance and tumors were coagulated with radiofrequency energy of 350 kHz. The needle electrodes were perfused with 0.9% saline during coagulation to increase the volume of coagulation necrosis without tissue vaporization. The serial changes in tumor size after therapy were evaluated with spiral CT imaging. Dynamic CT showed that unenhanced areas indicative of coagulation necrosis developed in all tumors. In 8 of 12 tumors no signs of recurrence appeared during the observation period of 7 (5-12) months. No major complications were observed. Our preliminary experience suggests that percutaneous radiofrequency coagulation can be a simple, safe and potentially effective treatment for selected patients with inoperable liver tumors. The results justify further studies to investigate the possible role in clinical practice.


Cave-adapted beetles from continental Portugal.
The cave biodiversity of continental Portugal faces tremendous conservation challenges, mostly linked to their direct destruction and contamination infiltrating from the surface. Beetles are the most diverse insects and one of the most diverse arthropod groups in caves of Portugal. We present the IUCN Red List profiles for the cave-adapted beetles from continental Portugal, all endemic to their respective geological units and massifs. Ground beetles (Carabidae) are the most diverse family of cave-adapted beetles in continental Portugal, followed by rove beetles (Staphylinidae). Beetles in caves of Portugal are mostly terrestrial and only one species is known to have evolved to live in groundwater. Trechus is the most diverse genus with four species, followed by Domene with three species and by Speonemadus and Iberoporus, both with one cave-adapted species. The aim of this contribution is to assess all endemic cave-adapted species of beetles from continental Portugal and to support their specific protection, to promote adequate management of surface habitats and the establishment of priority areas for conservation. The main biodiversity erosion drivers that are impacting the conservation of the studied species are pollution infiltrating from the surface, urbaniation, modifications of the natural habitat for touristic purposes and mining, quarrying and energy production infrastructures.This document can be used in spatial planning and territory management in karst, based on the current scientific knowledge.


Contrast enhancement of small hepatocellular carcinoma: usefulness of three successive early image acquisitions during multiphase dynamic MR imaging.
The purpose of this study was to document the usefulness of early triphasic image acquisition during gadolinium-enhanced multiphase dynamic MR imaging for the detection of contrast enhancement in small hepatocellular carcinoma. Dynamic MR imaging was performed in 332 patients at 1.5 T using a T1-weighted fast low-angle shot sequence (TR range/TE, 113-130/4.1; flip angle, 80 degrees). With the start of bolus injection of gadolinium dimeglumine (0.1 mmol/kg) into the antecubital vein, three sets of contrast-enhanced images of the entire liver were obtained serially at 10, 35, and 60 sec. Contrast enhancement of the tumor detected on each phase was evaluated in conjunction with the unenhanced T1-weighted images for 52 patients with small hepatocellular carcinomas up to 2 cm in diameter (n = 79). The first phase images depicted a larger number (n = 57) of contrast enhancement of small hepatocellular carcinoma tumors than the second (n = 44) or third phase images (n = 14). Twenty-six lesions were enhanced only during the first phase, and nine, during the second phase. The detection rate of contrast enhancement in the combination of first and second phases was the same as the overall detection rate for all three phases (70/79, 89%) and significantly higher than those of each phase. Early multiple image acquisition is helpful for the assessment of small hepatocellular carcinoma and is enabled by the high detection rate of contrast enhancement regardless of individual variations in the timing of enhancement.


Effect of transcutaneous electrical acupoint stimulation on remifentanil dosage during craniotomy aneurysm clipping: a prospective, randomized controlled study.
Craniotomy aneurysm clipping is one of the main treatments for intracranial aneurysm (IA). Endotracheal intubation and intraoperative operation may induce dramatic hemodynamic fluctuations and increase the risk of aneurysm rupture. Intraoperative high-dose opioid use is the main measure to reduce the intraoperative stress response, but it increases the incidence of complications such as postoperative vomiting and delayed awakening. Transcutaneous electrical acupoint stimulation (TEAS) stimulates β-endorphin expression levels and reduces opioid requirements. In this study, we aimed to assess the effects of TEAS on remifentanil dosage and oxidative stress (OS) in craniotomy aneurysm clipping. Forty-two patients with craniotomy aneurysm clipping were randomized into two groups: the TEAS group (T group) and the sham TEAS group (S group). "Hegu" (LI4), "Neiguan" (PC6) and "Zusanli" points (ST36) were selected, and a "HANS" percutaneous acupoint electrical stimulator was used for intervention 30 min before anesthesia induction until the end of the operation. The primary outcome was intraoperative remifentanil dosage. The secondary outcomes were intraoperative propofol dosage, mean arterial pressure (MAP) and heart rate (HR) 5 min before the TEAS intervention (T0), 5 min before head holder pinning (T1), immediately after pinning (T2), 5 min before craniotomy (T3), immediately after craniotomy (T4), at craniotomy (T5), and at the end of surgery (T6), as well as serum β-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100β, superoxide dismutase (SOD) and malondialdehyde (MDA) levels at T1, T2 and 24 h after surgery (T7). The dosage of remifentanil in the T group was reduced compared to that in the S group (P < 0.05). At T2, T4 and T5, the MAP and HR in the T group were lower than those in the S group (P < 0.05). At T2 and T7, the levels of NSE, S100β and MDA in group T were lower than those in group S (P < 0.05), while the SOD levels in group T were higher than those in group S (P < 0.05). The use of TEAS can reduce the dosage of remifentanil and reduce hemodynamic fluctuations during craniotomy aneurysm clipping. It reduces the occurrence of OS and central nervous system damage during surgery and has a certain brain protective effect. ChiCTR2100052353. https://www.chictr.org.cn/about.html .


[Effect of conditions of culturing Penicillium funiculosum G-15 on production of extracellular glucose oxidase].
Effects of conditions of Penicillium funiculosum G-15 cultivation on the production of extracellular glucose oxidase were studied. The data showed that surface and submerged methods of cultivation can be used for obtaining a glucose oxidizing enzyme. The optimum conditions for submerged cultivation (25 degrees C, initial pH 5.0, and aeration of 3 l/l per min) and surface cultivation (temperature 25 degrees C and initial pH 4.0) providing the maximum levels of glucose oxidase synthesis were determined.


Sequence variation and methylation of the flax 5S RNA genes.
The complete sequence of the flax 5S DNA repeat is presented. Length heterogeneity is the consequence of the presence or absence of a single direct repeat and the majority of single base changes are transition mutations. No sequence variation has been found in the coding sequence. The extent of methylation of cytosines has been measured at one location in the gene and one in the spacer. The relationship between the observed sequence heterogeneity and the level of methylation is discussed in the context of the operation of a correction mechanism.