Is it acceptable and feasible to measure prolonged grief disorder symptoms in daily life using experience sampling methodology?
Current grief research is dominated by cross-sectional studies assessing prolonged grief disorder (PGD) symptoms retrospectively. Examining grief in daily life, using Experience Sampling Methodology (ESM), may advance the field. Because of the lack of ESM-research on PGD, we evaluated the acceptability and feasibility of assessing PGD symptoms in daily life of bereaved people. ESM-items assessing PGD symptoms were developed using cognitive interviewing with five ESM/grief experts. Eighty bereaved adults completed these ESM-items five times a day for two weeks. Before and after this ESM-phase, interviews were administered assessing PGD retrospectively (using the Traumatic Grief Inventory-Clinical Administered). t-tests were performed comparing symptom severity of aggregated moment-to-moment recall (using ESM-items) with retrospective recall (based on interviews) of PGD symptoms. Acceptability of participating in ESM-research (assessed with the Reactions to Research Participation Questionnaire) was examined using descriptive statistics. Feasibility was evaluated by reporting compliance and retention rates. Minor changes were made to the ESM-items based on expert interviews. Average levels of aggregated moment-to-moment recall of the symptoms "yearning" (d = -1.04), "preoccupation with the deceased" (d = -0.91), "marked sense of disbelief" (d = -0.43), and "intense loneliness" (d = -0.28) were lower compared with retrospective recalling these symptoms. On average, bereaved people were neutral about personal benefits gained through participation in this EMS-study. They indicated that participation did not raise emotional reactions. Compliance and retention rates were 60% and 65%, respectively. Our findings indicate that whereas compliance and retention is challenging, using ESM to study PGD symptoms in daily life might be useful. Nevertheless, more research is needed.


Preparation of a star-shaped copolymer with porphyrin core and four PNIPAM-b-POEGMA arms for photodynamic therapy.
A series of thermosensitive star-shaped copolymers THPP-(PNIPAM-b-POEGMA)4 with 5, 10, 15,20-tetrakis-(4-hydroxyphenyl)-21H,23H-porphyrin (THPP) core and four poly(N-isopropy-lacrylamide)-b-poly(oligo(ethylene glycol) mono methyl ether methacrylate) (PNIPAM-b-POEGMA) arms were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The low critical solution temperatures (LCSTs) of THPP-(PNIPAM-b-POEGMA)4 with different molecular weights were 37.5 °C, 39.9 °C and 41.9 °C respectively, which depending on the hydrophilic POEGMA contents of copolymers. The micellar structures of copolymers could be formed above the LCSTs. The MTT study indicated that THPP-(PNIPAM-b-POEGMA)4 and THPP showed no significant cytotoxicity toward HeLa cells and L929 cells. And THPP-(PNIPAM-b-POEGMA)4 under light irradiation showed photodynamic activity which photo-toxicity toward HeLa cells was stronger than THPP.


Maintaining and reintroducing referents in French: cognitive constraints and development of narrative skills.
Seven- to eleven-year-old French-speaking children and adults told "silent" comic strip stories that differed by the frame display mode, by the explicitness of the links between depicted events, and whether the topic changed on the last frame. The results showed that (a) the character in the last frame was usually referred to as a given, with a definite pronoun when the topic was maintained and a definite noun phrase or a left dislocation when the topic changed; (b) joint display of frames triggered more pronouns and left dislocations, while single-frame display led to more definite noun phrases; and (c) explicit links gave rise to more pronouns. The production conditions manipulated turned out to be a good means of assessing speakers' acquisition of within-discourse referencing expressions and narrative skills: the children gradually refined and adjusted their use of definite expressions and pronouns, whereas the adults more readily used narration-specific devices.


Thiolated chitosans: Are Cys-Cys ligands key to the next generation?
The potential of Cys-Cys ligands for the development of a novel type of S-protected thiomers was evaluated. S-protected thiomers chitosan-N-acetylcysteine-mercaptonicotinamide (CS-NAC-MNA) and chitosan-N-acetylcysteine-N-acetylcysteine (CS-NAC-NAC) were synthesized and characterized. Viscosity of polymers in presence of various concentrations of S-amino acids was monitored. Mucoadhesive properties were evaluated. FT-IR characterization confirmed the covalent attachment of NAC-MNA and NAC-NAC. Attached sulfhydryl groups were found in the range of 550 μmol/g. In the presence of amino acids bearing a free thiol group viscosity of both polymers increased. This increase in viscosity depended on the amount of added free thiols. Maximum force required to detach CS-NAC-MNA and CS-NAC-NAC from porcine intestinal mucosa was 1.4- and 2.7-fold higher than that required for chitosan, respectively. CS-NAC-MNA adhered up to 3 h, whereas CS-NAC-NAC adhered even for 8 h on this mucosa. Accordingly, the Cys-Cys substructure could be identified as highly potent ligand for the design of mucoadhesive polymers.


Effects of Curcumin-mediated photodynamic therapy on autophagy and epithelial-mesenchymal transition of lung cancer cells.
This study aimed to investigated whether Curcumin-mediated PDT can suppress EMT in lung cancer cells, and explore the roles of autophagy in the process of regulating EMT. Lung cancer cell viability was assessed by CCK-8 assay. The expression of epithelial marker and mesenchymal markers, the conversion of LC3-I to LC3-II and the levels of p62 and beclin1 in A549 and SPCA1 cells were measured by Western blotting assay. The Wound healing and Transwell assays were used to detect the migration and invasion abilities of the A549 and SPCA1 cells. Autophagosome formation was detected via observing the colocalization of Lamp-2 with LC3 in A549 cells, and the autophagy ultrastructure was observed by TEM. Curcumin-PDT inhibited EMT, migration and invasion and induced autophagy in lung cancer cells. Curcumin-PDT induced autophagy was involved in the process of PDT inhibiting EMT, but it presented a promoting effect of EMT in lung cancer cells. Curcumin-PDT combined with CQ further inhibited EMT, invasion and migration of lung cancer cells. The role of PDT-induced autophagy in the regulation of EMT was determined to be a promoting effect in lung cancer. Therefore, Curcumin-mediated PDT combined with autophagy inhibitor further suppressed EMT of lung cancer cells, and may represent a potential strategy against invasion and migration of lung cancer.


Identification of essential sequences for cellular localization in the muscle-specific ubiquitin E3 ligase MAFbx/Atrogin 1.
In skeletal muscle atrophy, upregulation and nuclear accumulation of the Ubiquitin E3 ligase MAFbx is essential for accelerated muscle protein loss, but the nuclear/cytoplasmic shuttling of MAFbx is undefined. Here we found that MAFbx contains two functional nuclear localization signals (NLS). Mutation or deletion of only one NLS induced cytoplasmic localization of MAFbx. We identified a non-classical NES located in the leucine charged domain (LCD) of MAFbx, which is leptomycin B insensitive. We demonstrated that mutation (L169Q) in LLXXL motif of LCD suppressed cytoplasmic retention of MAFbx. Nucleocytoplasmic shuttling of MAFbx represents a novel mechanism for targeting its substrates and its cytosolic partners in muscle atrophy.


The histologic and molecular correlates of liver disease in fatal COVID-19 including with alcohol use disorder.
Hepatic disease is common in severe COVID-19. This study compared the histologic/molecular findings in the liver in fatal COVID-19 (n = 9) and age-matched normal controls (n = 9); three of the fatal COVID-19 livers had pre-existing alcohol use disorder (AUD). Controls showed a high resident population of sinusoidal macrophages that had variable ACE2 expression. Histologic findings in the cases included periportal/lobular inflammation. SARS-CoV2 RNA and nucleocapsid protein were detected in situ in 2/9 COVID-19 livers in low amounts. In 9/9 cases, there was ample in situ SARS-CoV-2 spike protein that co-localized with viral matrix and envelope proteins. The number of cells positive for spike/100× field was significantly greater in the AUD/COVID-19 cases (mean 5.9) versus the non-AUD/COVID-19 cases (mean 0.4, p < 0.001) which was corroborated by Western blots. ACE2+ cells were 10× greater in AUD/COVID-19 livers versus the other COVID-19/control liver samples (p < 0.001). Co-expression experiments showed that the spike protein localized to the ACE2 positive macrophages and, in the AUD cases, hepatic stellate cells that were activated as evidenced by IL6 and TNFα expression. Injection of the S1, but not S2, subunit of spike in mice induced hepatic lobular inflammation in activated macrophages. It is concluded that endocytosed viral spike protein can induce hepatitis in fatal COVID-19. This spike induced hepatitis is more robust in the livers with pre-existing AUD which may relate to why patients with alcohol abuse are at higher risk of severe liver disease with SARS-CoV2 infection.


Effect of DNA repair on the cytotoxicity and mutagenicity of polycyclic hydrocarbon derivatives in normal and xeroderma pigmentosum human fibroblasts.
The cytotoxicity of the "K-region" epoxides as well as several other reactive metabolites or chemical derivatives of polycyclic hydrocarbons was compared in normally-repairing human diploid skin fibroblasts and in fibroblasts from a classical xeroderma pigmentosum (XP) patient (XP2BE) whose cells have been shown to carry out excision repair of damage induced in DNA by ultraviolet (UV) radiation at a rate approx. 20% that of normal cells. Each compound tested exhibited a 2- to 3-fold greater cytotoxicity in this XP strain than in the normal strain. To determine whether this difference in survival reflected a difference in the capacity of the strains to repair DNA damage caused by such hydrocarbon derivatives, we compared the cytotoxic effect of several "K-region" epoxides in two additional XP strains, each with a different capacity for repair of UV damage. The ratio of the slopes of the survival curves for each of the XP strains to that of the normal strain, following exposure to each epoxide, was very similar to that which we had previously determined for their respective UV curves, suggesting that human cells repair damage induced in DNA by exposure to hydrocarbon derivatives with the same system used for UV-induced lesions. To determine whether the deficiency in rate of excision repair in this classical XP strain (XP2BE) causes such cells to be abnormally susceptible to mutations induced by "K-region" epoxides of polycyclic hydrocarbons, we compared them with normal cells for the frequency of induced mutations to 8-azaguanine resistance. The XP cells were two to three times more susceptible to mutations induced by the "K-region" epoxide of benzo(a)pyrene (BP), 7,12-dimethyl-benz(a)anthracene (DMBA), and dibenz(a,h)anthracene (DBA). Evidence also was obtained that cells from an XP variant patient are abnormally susceptible to mutations induced by hydrocarbon epoxides and, as is the case following exposure to UV, are abnormally slow in converting low molecular weight DNA, synthesized from a template following exposure to hydrocarbon epoxides, into large-size DNA.


Centre-surround effects on perceived orientation in complex images.
Using the simultaneous tilt illusion [Gibson, J., & Radner, M. (1937). Adaptation, after-effect and contrast in the perception of tilted lines. Journal of Experimental Psychology, 12, 453-467], we investigate the perception of orientation in natural images and textures with similar statistical properties. We show that the illusion increases if observers judge the average orientation of textures rather than sinusoidal gratings. Furthermore, the illusion can be induced by surrounding textures with a broad range of orientations, even those without a clearly perceivable orientation. A robust illusion is induced by natural images, and is increased by randomising the phase spectra of those images. We present a simple model of orientation processing that can accommodate most of our observations.


Detection of small testicular masses in monorchid patients using US, CPDUS, CEUS and US-guided biopsy.
Testis sparing surgery (TSS) is a well-known technique in the treatment of small testicular masses. Grayscale ultrasound (US), color/power Doppler US (CPDUS) and contrast-enhanced ultrasound (CEUS) are considered the best diagnostic imaging tools in those patients. Aim of this study was to assess the role of US imaging in the detection of small testicular masses in monorchid patients after orchiectomy for malignant neoplasm, and in guiding surgery to reach the target and also to differentiate lesions which presented vascular activity within the mass. From January 2011 to October 2014, 18 patients were enrolled in this study. They had previously undergone orchiectomy and were investigated for suspected contralateral disease. During routine follow-up, all patients underwent grayscale US. If findings were positive, CPDUS and CEUS were performed and eventually all patients underwent surgery. After exteriorization of the testis, the small mass was identified by intraoperative US, and a needle was placed under US guidance. After excision of the mass, frozen section examination was performed. When malignancy was found, radical orchiectomy was performed; if histological outcome was negative, the healthy testis was conserved. All patients underwent grayscale US examination, which showed small hypoechoic masses. Each mass identified at US imaging was confirmed at surgery. All patients underwent CPDUS; 12/19 lesions showed blood flow while 7/19 showed absence of blood flow. At CEUS, 16/19 lesions showed enhancement and subsequent histological examination revealed that 8 were seminomas and 3 were Leydig cell tumors. In 5/19 cases CEUS showed the presence of lesions (focal inflammatory lesions) and in 3/19 cases CEUS was negative. TSS in monorchid patients may be a safe procedure leading to excellent results. We therefore consider it a valid alternative to radical orchiectomy, and US imaging is essential to guide the resection of non-palpable neoplasms and to exclude concomitant lesions.


Trypanosoma cruzi genotypes associated with domestic Triatoma sordida in Bolivia.
Triatoma sordida is the second species of Triatominae considered of epidemiological significance in Bolivia. Associated with Triatoma infestans in various regions, it is as yet the only triatomine species established in human dwellings in localities of Velasco province, Department of Santa Cruz. This domestication is considered as primary. Flagellate parasites were detected in 16.2% of domiciliary T. sordida and the kDNA-PCR confirmed the presence of Trypanosoma cruzi. Frequencies of T. cruzi clonets 20 and 39, common clonets in Bolivian domestic cycle (T. infestans), were established by their direct detection in feces using PCR and hybridization. These clonets present low frequencies in T. sordida and synanthropic mammals. Forty-six stocks were isolated and analysed by multilocus enzyme electrophoresis (MLEE). The MLEE showed a higher clonal diversity than in T. infestans domestic cycle and the genotypes were clustered in the two principal lineages of T. cruzi. Within each lineage, a broad variability was observed. Mixture of genotypes was mostly observed in mammals. The large diversity of T. cruzi in this cycle should be related to its sylvatic origin. Moreover, the current limited sample of stocks suggests a lineage association with specific hosts.


Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell line derived from rat aortic smooth muscle.
Nicorandil opens adenosine triphosphate-sensitive potassium (K(ATP)) channels in the cardiovascular system and is being increasingly used for the treatment of angina pectoris. In the present study, we tested whether intravenous anesthetic agent ketamine affected nicorandil-induced native vascular K(ATP) channel activation. We used excised inside-out patch clamp configurations to investigate the direct effects of ketamine racemate and S-(+)-ketamine on the activities of K(ATP) channels in cultured rat aortic smooth muscle cells. Furthermore, we also investigated whether intracellular MgADP could modulate ketamine inhibition. Nicorandil significantly activated K(ATP) channel activity, whereas this channel activity was completely blocked by glibenclamide, a specific K(ATP) channel blocker. Ketamine racemate inhibited the nicorandil induced K(ATP) channel activity (IC(50)=34±1 µM, n=14), but S-(+)-ketamine was less potent than ketamine racemate in blocking nicorandil induced K(ATP) channel activities (IC(50)=226±7 µM, n=10). Application of MgADP to the intracellular side of the channel was able to decrease the inhibitory potency of ketamine racemate on nicorandil induced K(ATP) channel activities. Our results indicate that ketamine inhibits nicorandil induced K(ATP) channel activities in a dose dependent and stereoselective manner. Furthermore, increase of intracellular MgADP attenuates the inhibitory potency of ketamine racemate. J. Med. Invest. 57: 237-244, August, 2010.


Therapeutic potential of Kupffer cells in prevention of liver metastases outgrowth.
Development of liver metastases is a frequent complication in the course of gastro-intestinal malignancies. After entering the liver via the portal circulation, blood-borne tumor cells that have been seeded from primary colorectal cancer, are first encountered by Kupffer cells (KC), which line the liver sinusoids. KC represent approximately 10% of all liver cells, and have the ability to kill tumor cells. As such, they may play an important intrinsic role in the protection against outgrowth of hepatic metastases. Furthermore, the cytotoxic function of KC is increased upon stimulation with various biological response modifiers, such as interferon-gamma, granulocyte macrophage-colony stimulating factor, antibodies and muramyl dipeptides. Therefore, enhancement of KC cytotoxic functions may represent an attractive treatment modality to prevent development of liver metastases in the clinical setting.


The influence of urinary macromolecules on calcium oxalate monohydrate crystal growth.
The Constant Composition (CC) kinetics method has been used for studying the mineralization of calcium oxalate monohydrate (COM) at sustained supersaturations in the presence of pre-bladder urine and macromolecules isolated from normal urine and kidney and bladder stones. The method is especially sensitive for investigating the inhibitory activities of these urinary macromolecular components (UMMC) and matrix macromolecular components (MMMC) with a coefficient of variation in growth rate of approximately 2%. Significant COM mineral inhibition was observed in a wide molecular weight region of urine components. Urine removed directly from the kidney showed appreciable inhibitory activity towards COM crystallization. Normal urinary proteins and the dissolved precipitate resulting from urine centrifugation were fractionated by gel filtration. The resulting solutions were mostly COM mineralization inhibitors. Electrodialysis was utilized to isolate the MMMC (greater than 7000 d) of renal and bladder calculi. While these solutions inhibited COM crystallization, they were also found to be calcium binders as measured by the calcium electrode.


The Laugier-Hunziker syndrome.
Laugier and Hunziker described a syndrome consisting of asymptomatic benign areas of hyperpigmentation affecting the lips, buccal mucosa and, in 50%, the fingernails. We report a 67-year-old woman with the clinical features of Laugier-Hunziker syndrome in association with vulval pigmentation. Histology, immunohistochemistry and electron microscopy from the various areas of pigmentation on the body confirmed the benign nature of the pigmentation. We review potential causes of oral and genital pigmentation, and suggest an expansion of the original syndrome described by Laugier and Hunziker to include more widespread areas of benign hyperpigmentation, which may associated.


Diagnosis and Treatment of Kaposi Sarcoma.
Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa, KS is among the most common cancers in men, overall. Not only HIV-positive individuals present with KS; any immune compromised person infected with KS-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein latency-associated nuclear antigen (LANA) in the biopsy, but not all cases of KS are the same or will respond to the same therapy. Standard KS therapy has not changed in 20 years, but newer modalities are on the horizon and will be discussed.


[The flea infestation of small alpine mammals and its dependence on the time of the year and altitude].
The infestation of small alpine mammals with fleas during the year and at different altitudes was investigated. The data are based on an investigation carried out between 1966 and 1969 in Tirol (Austria) in different altitudinal zones of the alps, 1136 fleas having been collected from 625 insectivores and rodents. By comparing the collections from the lower and higher regions and from different seasons of the year details of the pattern of distribution can be given for some species of fleas (e.g. for Doratopsylla dasycnema, Palaeopsylla soricis, Ctenophthalmus orphilus, Amphipsylla sibirica sepifera, Peromyscopsylla bidentata, P. fallax). The hosts in the subalpine and alpine zone proved to be less infested by fleas than the mammals of the lower regions, during the warm season the hosts harboured more parasites than during winter. Extensiveness and intensity of infestation were constantly higher in Soricidae than in Muridae.


Removal of mango-flavoured Juul pods created opportunity for adulterated mango Juul-compatible pods with altered chemical constituents.
Juul is a leading electronic cigarette (e-cigarette) brand in the USA. By November 2019, Juul pre-emptively limited online and in-store sales of non-tobacco or menthol-flavoured pods ahead of impending flavour bans. Since this removal, sale of mango-flavoured Juul-compatible pods was introduced to the market by smaller companies. The aim of this study was to compare chemical constituents of original Juul mango pods with mango-flavoured Juul-compatible pods. Juul and 16 brands of Juul-compatible mango-flavoured pods were purchased online in May 2018 (original Juul) and November 2019 (Juul-compatible), after Juul voluntarily removed their flavoured pods from the market. Liquid was extracted from pods and analysed using chromatography and mass spectrometry methods for nicotine concentration, solvent ratios, nicotine salt identification, as well as flavouring identification and quantitation. Juul-compatible pods had a significantly lower average nicotine concentration compared with original Juul pod (42.8±8.9 vs 57.2±0.9 mg/mL, p<0.0001). Nicotine benzoate was used in original Juul pod and all Juul-compatible pods. The propylene glycol to vegetable glycerin volumetric ratio of Juul-compatible pods averaged 55:45, while the original Juul pod was 35:65 (p<0.0001). Total number of flavouring chemicals detected was significantly higher in Juul-compatible pods as compared with Juul (p<0.0001). In Juul-compatible pods, average concentrations of benzyl alcohol (fruity flavouring) were 0.8±1.3 mg/mL, approximately 27 times higher than in original Juul pod (p<0.0001). Adulterated Juul-compatible products may expose e-cigarette consumers to more chemical constituents at higher concentrations than previously found in the original product, despite similarity in product design.


Sodium alendronate is an effective adjunctive therapy for treating periodontitis in male rats treated with anticancer chemotherapy.
To assess sodium alendronate as a local adjunctive therapy for treating experimental periodontitis in male rats treated with chemotherapy. One-hundred-eighty male rats were randomly divided into two groups (n = 90) based on the systemic treatments: PSS, physiological saline solution; and 5-Fluorouracil, and then, subdivided into three subgroups (n = 30): NT, no treatment; scaling and root planing; and sodium alendronate. Treatments were performed 7 days after induction of experimental periodontitis. Specimens were collected at 14, 22, and 37 days after induction. Alveolar bone level, percentage of bone in the furcation, percentage of non-vital bone in the furcation, histopathologic features, and immunolabeling pattern for tartrate-resistant acid phosphatase (TRAP) and osteocalcin (OCN) were evaluated. The lowest amount of alveolar bone and highest amount of non-vital bone was found in group 5-Fluorouracil when no treatment was performed. In animals receiving 5-Flurouracil and subjected to periodontal treatment, adjunctive sodium alendronate resulted in higher percentage of bone in the furcation and higher alveolar bone loss, when compared with scaling and root planing alone. Better structural and cellularity patterns were found in the periodontal tissues when sodium alendronate was used, regardless of systemic treatment. Higher TRAP-expression was found when no treatment was performed. Sodium alendronate didn't affect the immunolabeling pattern of osteocalcin in the presence of 5-Fluorouracil. Adjunctive therapy with local sodium alendronate prevented alveolar bone loss and improved the histopathological features of the periodontal tissues following scaling and root planing in male rats with experimental periodontitis receiving anticancer chemotherapy with 5-Fluorouracil.


Activation of natural killer cells and cytokine production in humans by bacterial extracts (OM-85 BV).
The influence of Broncho-Vaxom (BV) on different immune parameters was investigated in vitro on human peripheral blood mononuclear cells (PBMC). It was found that BV enhances the natural killer (NK) activity of PBMC and increases their spontaneous and phytohemagglutin (PHA)-induced production of tumor-necrosis factor--alpha and interleukin-2 as well as the PHA-stimulated production of interferon-gamma. These immunostimulating actions of BV on NK activity and cytokine production can contribute to the understanding of the enhancement of the body's defense mechanisms against respiratory tract infections.


Evaluation of genetic polymorphisms in patients with multiple chemical sensitivity.
Multiple chemical sensitivity (MCS) is a chronic medical condition characterized by symptoms that the affect an individual's response to low-level chemical exposure. In this study, we identified a chemical sensitive population (CSP) and investigated the effect of genetic polymorphisms on their risk of chemical sensitivity. A quick environment exposure sensitivity (QEESI) questionnaire was used to survey 324 Japanese male workers whose DNA samples had been collected and stored. The following genes, which encode enzymes affecting the metabolic activation of a large number of xenobiotic compounds, were selected and analyzed in order to determine their influence on genetic predisposition to CSP: cytochrome P450 (CYP) 2E1, N-acetyl transferase (NAT) 2, glutathione S-transferase (GST) M1, GSTT1, GSTP1, low Km aldehyde dehydrogenase (ALDH2), and superoxide dismutase (SOD) 2. Significant case-control distributed differences were observed in SOD2 polymorphisms and allele frequency distribution in high chemical sensitive subjects. Both the significant adjusted OR of 4.30 (95% CI, 1.23-15.03) and 4.53 (95% CI, 1.52-13.51) were observed in SOD2 Ala/Ala and Val/Ala compared to Val/Val and in SOD2 Ala/Ala compared to Val/Ala compared to Val/Val genetic analysis in the high chemical sensitivity case-control study. We observed that high chemical sensitive individuals diagnosed by using Japanese criteria as MCS patients were more significantly associated with SOD2 polymorphisms.


Country ownership and sustainability of Nigeria's HIV/AIDS Supply Chain System: qualitative perceptions of progress, challenges and prospects.
The emergency response phase to HIV epidemic in Nigeria and other countries saw to the deployment of donors' resources with little consideration for country ownership (CO) and sustainability. The progress that has been made in the fight against the pandemic has however precipitated a paradigm shift towards CO and sustainability. With the decline in donors' funding, countries must continually evaluate their readiness to own and sustain their HIV response especially the supply chain system (SCS) and bridge any observed gaps. This study assessed the current understanding of CO and sustainability of Nigeria's HIV/AIDS SCS, established progress that has been made, identified challenges that may be hampering CO and possible recommendations to address these challenges. It also explored opportunities that the country can leverage on. We conducted a cross sectional descriptive study through semi-structured interview of twelve purposefully selected key informants involved in HIV/AIDS supply chain management. Transcribed qualitative data were analyzed using a thematic approach. Among other submissions, respondents acknowledged that CO involves non-government stakeholders. Key CO and sustainability achievements were: development of national strategic plans and policy documents, establishment of coordinating structures, allocation of funds for some logistics activities at the state level and payment of salaries of government staff, institution of pre-service training, use of logistics data for decision making and the unification of the hitherto parallel HIV/AIDS supply chains. Challenges included: inadequate domestic funding, bureaucratic bottlenecks and inadequate manpower at the health facility level. Respondents recommended more political commitment and increased government funding, exploration of alternative sources of funding, improved accountability, effective healthcare workforce planning and local manufacture of HIV commodities. Existing structures and programmes that the country can leverage on included: Nigeria Supply Chain Integration Project, National Health Insurance Scheme and the private sector. Nigeria has made some progress towards achieving CO and sustainability. The country however needs to address financial and human resource gaps through innovative resource mobilization and effective workforce planning. As other countries plan for CO and sustainability, it is important to secure political buy-in and adopt a working definition for CO and sustainability while resource mobilization and workforce planning should be prioritized.


A Monocentric Retrospective Study about the Correlation between Histology and Cytology of Thyroid Indeterminate Nodules Classified as TIR 3A and TIR 3B, according to 2014 Italian Consensus for Classification and Reporting of Thyroid Cytology.
In 2014, the Italian Consensus for Classification and Reporting of Thyroid Cytology (ICCRTC) reviewed the previous cytological classification proposed in 2007 including the subdivision of TIR 3 category into low risk (TIR 3A) and high risk (TIR 3B). In Italian literature, different rates of malignancy have been correlated to these subcategories. The aim of the study is to present our experience on this subclassification for the assessment of the malignancy risk of indeterminate thyroid nodules. We correlated the subdivision into TIR 3A and TIR 3B with the histological report by highlighting the rates of malignancy detected in the two subcategories. On the one hand, we aimed to check if the groups are associated with a real and significant difference risk of malignancy. On the other hand, we evaluated the use of this subdivision in the choice of the appropriate treatment. This is a retrospective review of all the patients with an indeterminate nodule who underwent US-FNA and had surgery at ASL Città di Torino between January 2005 and May 2018. 150 patients have been analyzed for the research; 62 (41.3%) had a malignant histological report. Rates of malignancy between TIR 3A (20.8%) and TIR 3B (60.3%) were significantly different (p < 0.0001). The subclassification had high sensitivity (75.8%; CI 63.3-85.8%) and NPV (79.3%; CI 68-87.8%) and low specificity (64.8%; CI 53.9-74.7%) and PPV (60.3; CI 48.5-71.2%). The measurement of the accuracy (AUC = 0.7) classified the test as "moderately accurate." Conclusions. Obtained data show a great rate of false negative (20.8%) and limited AUC (0.7). According to our logistic regression, we argue that the 2014 subclassification into TIR 3A and TIR 3B should be considered for the choice of patient treatment, but at the same time, we believe that the association with other screening tests is necessary to increase the accuracy in the future.


Allergic and irritant contact dermatitis compared in the treatment of alopecia totalis and universalis. A comparison of the value of topical diphencyprone and tretinoin gel.
Diphencyprone is a potent topical sensitizer, but is non-mutagenic in the Ames test (unlike dinitroclorobenzene) and remains relatively stable in solution (unlike squaric acid dibutyl ester). Seventeen patients with total loss of scalp hair (eight alopecia totalis, nine alopecia universalis) were treated by maintaining on one side of the scalp an allergic contact dermatitis induced by 2,3 diphenylcyclopropenone-I ('diphencyprone'), and on the other side an irritant contact dermatitis using tretinoin gel (Retin A). After 20 weeks, treatment with tretinoin was stopped and diphencyprone was applied bilaterally for a further 10 weeks. Satisfactory regrowth of terminal hair on the scalp was achieved in only one patient. Eyebrow, eyelash and beard regrowth was achieved in one individual whilst in another, moderate, but not cosmetically satisfactory, scalp regrowth took place. In no patient did regrowth take place at tretinoin treated sites until after diphencyprone was substituted.


Adaptability of "Management of Really Sick Patients with Anorexia Nervosa" (MARSIPAN) for extreme anorexia nervosa in a developing country: A case report.
For the management of patients with severe eating disorders, coordinated collaboration between a multidisciplinary team is imperative. Ideally, these cases should be treated in a specialized eating disorder unit (SEDU). This case report highlights the use of an integrated approach based on "Management of Really Sick Patients with Anorexia Nervosa" report in managing a case of extreme anorexia nervosa where a SEDU is unavailable. In this case, early psychiatric team support is key in the patient's path to recovery. This highlights the importance of having a SEDU and staff trained in eating disorder.


Alpinetin: a Dietary Flavonoid with Diverse Anticancer Effects.
Cancer is a global burden and mechanistically complex disease with a plethora of genetic, physiological, metabolic, and environmental alterations. The development of dietary nutraceuticals into cancer chemotherapeutics has emerged as a new paradigm in cancer treatment. Alpinetin (ALPI) is a novel flavonoid component of multiple edible and medicinal plants and possesses a wide range of biological and pharmacological activities including antibacterial, anti-hemostatic, anti-oxidative, anti-hepatotoxic, stomachic, immunosuppressive, and anti-inflammatory. Recently, ALPI has been reported as a bioactive dietary nutraceutical with promising anticancer activity in various human cancers through multiple mechanisms. The purpose of this review is to compile the data on natural sources of ALPI, and its anticancer activity including cellular targets and anticancer mechanism in various human cancers. Moreover, this review will set the stage for further design and conduct pre-clinical and clinical trials to develop ALPI into a lead structure for oncological therapy.


Production and antimicrobial activity of trans-resveratrol, trans-arachidin-1 and trans-arachidin-3 from elicited peanut hairy root cultures in shake flasks compared with bioreactors.
Obtaining large-scale hairy root cultures is a major challenge to increasing root biomass and secondary metabolite production. Enhanced production of stilbene compounds such as trans-resveratrol, trans-arachidin-1 and trans-arachidin-3 was achieved using an elicitor treatment procedure. Two different hairy root inoculum densities were investigated and compared between shake flask and bioreactor cultures. The lowest growth index was observed using a 20 g/L inoculum size in the bioreactor, which differed significantly from bioreactor of 5 g/L. Increasing the hairy root inoculum size from 5 g/L to 20 g/L in both the shake flask and bioreactor significantly improve antioxidant activity, phenolic content and stilbene compound levels. The highest ABTS and FRAP antioxidant activity, and levels of total phenolic compounds, trans-arachidin-1 and trans-arachidin-3 in the crude extract were demonstrated in shake flask cultures with a 20 g/L inoculum after elicitation for 72 h. The minimum inhibitory concentrations (MICs) of the crude extract to inhibit growth of foodborne microbes, S. aureus, S. typhimurium and E. coli, were 187.5, 250 and 500 μg/mL, respectively. This was due to the ability of the crude extract to disrupt the cell membrane, as observed by scanning electron microscopy (SEM) showing ruptured pores on the S. aureus and S. typhimurium cell surfaces. Moreover, the E. coli cell division process could be inhibited by the crude extract, which promoted an increase in cell size. A DNA nicking assay indicated that a 50 μg/mL concentration of the crude extract caused plasmid DNA damage that might be due to a genotoxic effect of the pro-oxidant activity of the crude extract.


LIF signaling in stem cells and development.
Leukemia inhibitory factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. All members of this family activate signal transducer and activator of transcription 3 (STAT3), a transcription factor that influences stem and progenitor cell identity, proliferation and cytoprotection. The role of LIF in development was first identified when LIF was demonstrated to support the propagation of mouse embryonic stem cells. Subsequent studies of mice deficient for components of the LIF pathway have revealed important roles for LIF signaling during development and homeostasis. Here and in the accompanying poster, we provide a broad overview of JAK-STAT signaling during development, with a specific focus on LIF-mediated JAK-STAT3 activation.


Rank ligand as a target in musculoskeletal neoplasms.
Receptor activator of nuclear factor-κB ligand (RANKL) is a tumor necrosis factor (TNF) family member, which signals through the osteoclast surface RANK. As such, RANKL is required for osteoclast differentiation and function, namely bone resorption. There is now growing evidence that RANKL is a therapeutic target for musculoskeletal neoplasms, namely giant cell tumor of bone (GCTB) and osteosarcoma.


A comparison of voluntary and forced exercise in protecting against behavioral asymmetry in a juvenile hemiparkinsonian rat model.
Several studies have found a neuroprotective effect of forced exercise in rodent Parkinson's disease models; however, the evidence for the protective effect of voluntary exercise is mixed. Most of these studies have initiated the exercise after toxin-induced hemiparkinsonism. Few studies have investigated the role of a preconditioning of exercise prior to neurotoxic insult. Therefore, the purpose of this study was to explore the neuroprotective effect of regular forced and voluntary exercise in recently weaned rat pups prior to an adult hemiparkinsonian lesion. Recently weaned rat pups were randomized into four 6-week experimental groups: forced exercise, voluntary exercise, control, and a sham surgery control. After participation in a 6-week experimental condition, hemiparkinsonism was induced using a unilateral injection of 6-hydroxydopamine (6-OHDA). Parkinsonian behavioral tests (i.e., apomorphine rotations, forelimb placement asymmetry, exploratory rearing) demonstrated significant motor asymmetry for all three 6-OHDA group; however, there were no significant differences among them. The sham control rats did not show motor impairment consistent with nigrostriatal motor deficits. Neither a preconditioning of forced nor voluntary exercise was neuroprotective of a future 6-OHDA lesion. These results are in contrast to the literature and suggest that exercise neuroprotection may not be so straightforward.


Assessment of Drug-drug Interaction and Optimization in Capecitabine and Irinotecan Combination Regimen using a Physiologically Based Pharmacokinetic Model.
Capecitabine and irinotecan (CPT-11) combination regimen (XELIRI) is used for colorectal cancer treatment. Capecitabine is metabolized to 5-fluorouracil (5-FU) by three enzymes, including carboxylesterase (CES). CES can also convert CPT-11 to 7-ethyl-10-hydroxycamptotecin (SN-38). CES is involved in the metabolic activation of both capecitabine and CPT-11, and it is possible that drug-drug interactions occur in XELIRI. Here, a physiologically based pharmacokinetic (PBPK) model was developed to evaluate drug-drug interactions. Capecitabine (180 mg/kg) and CPT-11 (180 mg/m2) were administered to rats, and blood (250 μL) was collected from the jugular vein nine times after administration. Metabolic enzyme activities and Ki values were calculated through in vitro experiments. The plasma concentration of 5-FU in XELIRI was significantly decreased compared to capecitabine monotherapy, and metabolism of capecitabine by CES was inhibited by CPT-11. A PBPK model was developed based on the in vivo and in vitro results. Furthermore, a PBPK model-based simulation was performed with the capecitabin dose ranging from 0 to 1000mol/kg in XELIRI, and it was found that an approximately 1.7-fold dosage of capecitabine was required in XELIRI for comparable 5-FU exposure with capecitabine monotherapy. PBPK model-based simulation will contribute to the optimization of colorectal cancer chemotherapy using XELIRI.


Early Depression Independently of Other Neuropsychiatric Conditions, Influences Disability and Mortality after Stroke (Research Study-Part of PROPOLIS Study).
Post-stroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. The nature of the relationship between PSD and mortality still remains unknown. One hypothesis is that PSD could be more frequent in those patients who are more vulnerable to physical disability, a mediator variable for higher level of physical damage related to higher risk of mortality. Therefore, the authors' objective was to explore the assumption that PSD increases disability after stroke, and secondly, that mortality is higher among patients with PSD regardless of stroke severity and other neuropsychiatric conditions. We included 524 consecutive patients with acute stroke or transient ischemic attack, who were screened for depression between 7-10 days after stroke onset. Physical impairment and death were the outcomes measures at evaluation check points three and 12 months post-stroke. PSD independently increased the level of disability three (OR = 1.94, 95% CI 1.31-2.87, p = 0.001), and 12 months post-stroke (OR = 1.61, 95% CI 1.14-2.48, p = 0.009). PSD was also an independent risk factor for death three (OR = 5.68, 95% CI 1.58-20.37, p = 0.008) and 12 months after stroke (OR = 4.53, 95% CI 2.06-9.94, p = 0.001). Our study shows the negative impact of early PSD on the level of disability and survival rates during first year after stroke and supports the assumption that depression may act as an independent mediator for disability leading to death in patients who are more vulnerable for brain injury.


Visitor characteristics and alcohol-based hand sanitizer dispenser locations at the hospital entrance: Effect on visitor use rates.
Hospital visitors' hand hygiene (HH) is an important aspect of preventing health care-associated infections, but little is known about visitors' use of alcohol-based hand sanitizers (AHS). The study aim was to examine if use of AHS is influenced by visitor characteristics and the location of AHS within the lobby of a large hospital. An observational study was conducted with AHS placed in 3 different locations. The data included visitor characteristics and if AHS were used. The results suggest that visitors are 5.28 times (95% confidence interval [CI], 3.68-7.82) more likely to use AHS when dispensers are located in the middle of the lobby with limited landmarks or barriers, 1.35 times more likely to use the AHS in the afternoon compared with the morning, or when they are younger visitors (adjusted odds ratio, 1.47; 95% CI, 1.09-1.97). Individuals in a group are more likely (adjusted odds ratio, 1.39; 95% CI, 1.06-1.84) to use AHS. In addition to location, time of day, and age, there is a group effect that results in visitors being more likely to use AHS when in a group. The increased use related to groups may serve as a mechanism to encourage visitor HH. The results suggest future research opportunities to investigate the effect of group dynamics and social pressure on visitor AHS use and to identify strategies for improving visitor HH.


Intraductal Papillomas.
The most common manifestation of papillary breast disease is intraductal papilloma (IDP). As breast disease management becomes more refined, increasing attention has been directed at determining which IDPs require excision, and which can be monitored. This article will discuss the most common factors currently impacting personalized decision-making.


An experimental investigation of recruitment bias in eating pathology research.
Previous, uncontrolled research has suggested a bias may exist in recruiting participants for eating disorder research. Recruitment biases may affect sample representativeness and generalizability of findings. This experiment investigated whether revealing that a study's topic was related to eating disorders created a self-selection bias. Young women at a university responded to advertisements containing contrasting information about the nature of a single study. We recruited one group by advertising the study under the title "Disordered Eating in Young Women" (n = 251) and another group using the title "Consumer Preferences" (n = 259). Results indicated similar levels of eating pathology in both groups, so the different recruitment techniques did not engender self-selection. However, the consumer preferences group scored higher in self-reported social desirability. The level of information conveyed in study advertising does not impact reporting of eating disturbances among nonclinical samples, although there is evidence social desirability might.


Pseudomyxoma peritonei of appendiceal origin. The Memorial Sloan-Kettering Cancer Center experience.
Pseudomyxoma peritonei is a rare clinical entity in which the peritoneal surfaces and omentum are involved with diffuse gelatinous mucinous implants. It originates from ruptured mucinous tumors of the appendix or ovary. The authors examined the experience with 34 patients with pseudomyxoma peritonei seen at Memorial Sloan-Kettering Cancer Center from 1952-1989. Of these, 17 cases were identified to be of appendiceal origin. All patients underwent celiotomy and cytoreduction. The median survival time from diagnosis was 75 months. It was found that long-term survival can be achieved by operation alone. When conditions do recur, chemotherapy may be valuable. Pseudomyxoma peritonei of appendiceal origin is a rare low-grade malignancy. Initial treatment consists of cytoreduction in an attempt to render the patient locally disease-free. Long-term survival can be obtained by operation alone, even if gross disease is present at the end of the procedure. Systemic chemotherapy should be reserved for patients with proven recurrence.


Pancreatic metastasis of leiomyoma found 27 years after uterine fibroid surgery.
A 59-year-old female was referred to our hospital for pancreatic tumor. She had undergone resection of uterine fibroids 27 years ago, and leiomyoma in the left thigh 8 years ago. Tumor markers were normal. A well-defined hypoechoic tumor measuring 26 mm × 22 mm was detected at the pancreatic tail using ultrasound. Inside the tumor, a small cystic structure was observed. High-sensitivity Doppler imaging revealed faint signals indicating blood flow from the periphery to the interior. Contrast-enhanced ultrasonography in the arterial phase revealed slow, heterogenous enhancement from the periphery to the center of the mass that occurred later than that in the pancreatic parenchyma. The tumor then exhibited homogeneous enhancement except for the periphery, with subsequent washout. Endoscopic ultrasound-fine-needle aspiration was performed. Histopathological examination diagnosed a leiomyoma. The left thigh tumor resected 8 years ago had been diagnosed as benign metastatic leiomyoma (BML). We considered that the current pancreatic tumor was also BML clinically. We report this case because pancreatic metastasis from uterine fibroids is extremely rare. Uterine fibroids are benign tumors, but there are rare cases of metastasis to various organs, which should be considered when performing ultrasound.


Nutritional evaluation of children with chronic cholestatic disease.
To evaluate the nutritional status of children with persistent cholestasis and to compare the anthropometric indices between children with and without liver cirrhosis and children with and without jaundice. Children with persistent cholestasis, i.e. increased direct bilirrubin or changes in the canalicular enzyme gamma-glutamyl transferase (GGT), were included. The anthropometric measures were weight (W), height or length (H), arm circumference (AC), triceps skinfold thickness (TST), arm muscle circumference (AMC), and body mass index (BMI). Ninety-one children with cholestasis, with current median age of 12 months, were evaluated. W/age (A) and H/A indices below -2 Z-scores were observed in 33% and 30.8% of patients, respectively. Concerning the W/H index and BMI, only 12% and 16% of patients, respectively, were below -2 Z-scores. Regarding AC, 43.8% of 89 evaluated patients had some depletion. Observing the TST, 64% of patients had depletion, and 71.1% of the 45 evaluated patients had some degree of depletion regarding the ACM index. Evaluation using weight in patients with chronic liver diseases may overestimate the nutritional status due to visceromegaly, subclinical edema, or ascites. Indices that correlate weight and height, such as W/H and BMI, may also not show depletion because of the chronic condition in which there are depletion of both weight and height. TST, AC, and ACM are parameters that better estimate nutritional status and should be part of the management of patients with liver diseases and cholestasis.


Does economic policy uncertainty drive outbound tourism expenditures in 20 selected destinations?
Across several destinations, tourism receipts and the aspects of tourism industry has continued to influence the quality of life of the people as well contributing to the national development and sustainable growth. However, the uncertainties and risks experienced in the tourism industry and other economy sectors have remained the drawback of most economies and destinations. As such, the panel of 20 selected destinations is investigated via the common correlated effect method to examine the nexus of economic policy uncertainty and tourism development over the period 2001-2017. Interestingly, the result established a long term relationship between the economic policy uncertainty index and outbound tourism expenditures. Specifically, the finding revealed that outbound tourism expenditures are affected negatively by the rise of uncertainty in economic policies, thus suggesting instability of economic-related policy is the bane of tourism development in the destinations. This result stands to have important policy guide for especially for tourism-related activities in the panel of 20 selected countries.


Impacts of repeated retrieval of positive and neutral memories on posttrauma health: An investigative pilot study.
Evidence indicates that positive memory processes play a role in the etiology and maintenance of posttraumatic stress symptoms (PTSS) and related posttrauma health indicators. To extend this research, the current pilot study examined if repeated retrieval of positive vs. neutral memories was associated with (1) less PTSS and depression severity; and (2) improved affect and cognitions (fewer posttrauma cognitions, more positively-valenced affect, less negatively-valenced affect, less negative affect interference, less anhedonia, retrieval of more positive specific memories, retrieval of fewer negative specific memories). Twenty-five trauma-exposed participants were randomly assigned to a positive or neutral memory task condition. They participated in four weekly experimental sessions facilitated by an experimenter virtually; each consecutive session was separated by 6-8 days. We conducted mixed between-within subjects ANOVAs to examine study hypotheses. No interaction effects were significant. There were significant main effects of time on PTSS and depression severity, posttrauma cognitions, positively-valenced and negatively-valenced affect, and negative affect interference. We used self-report measures, small and non-clinical sample with limited demographic diversity, and virtual format; did not record memory narratives; and did not have a trauma memory condition. Based on pilot data, our findings suggest that individuals who retrieve positive or neutral memories repeatedly may report less PTSS and depression severity, fewer posttrauma cognitions, and improved affect. Results provide an impetus to examine impacts of and mechanisms underlying memory interventions (beyond a sole focus on negatively-valenced memories) in trauma work.


Epithelial breakthrough during IntraLase flap creation for laser in situ keratomileusis.
We report the clinical manifestations and outcomes in 4 patients who experienced premature gas-bubble leakage during raster lamellar dissection during IntraLase femtosecond laser corneal flap creation. Three patients experienced a full-thickness epithelial breakthrough and the fourth, a flap tear. The patient who experienced the flap tear was unable to have laser in situ keratomileusis successfully. The flap complications did not result in a decreased best corrected visual acuity in any patient but may have resulted in epithelial ingrowth in one and a corneal scar and microstriae in another. Potential predisposing factors for epithelial breakthrough, the incidence of epithelial breakthrough, and methods for avoiding and salvaging traumatic corneal flaps are discussed.


[The additive synthesis of a regulatory peptide in vivo: the administration of a vaccinal Francisella tularensis strain that produces beta-endorphin].
It has been shown, that vaccine strain of tularemia microbe, F.T.ISE., which produced recombinant beta-endorphin, when administered to CBA mice. It was shown to increase in the threshold level of pain sensitivity and is associated with peptides associated changes the stereotypic behavior. The observed correlated in time with the pattern of the dynamics of culture in the experimental animals and were associated with the level of recombinant beta-endorphin synthesis.


Phenotyping jasmonate regulation of senescence.
Osmotic stress induces several senescence-like processes in leaves, such as specific changes in gene expression and yellowing. These processes are dependent on the accumulation of jasmonates and on intact jasmonate signaling. This chapter describes the treatment of Arabidopsis thaliana leaves with sorbitol as an osmotic stress agent and the determination of the elicited phenotypes encompassing chlorophyll loss, degradation of plastidial membrane lipids, and induction of genes regulated by senescence and jasmonate.


The incidence of atrial fibrillation and the use of warfarin in Northland, New Zealand stroke patients.
To identify the number of Northland stroke patients with atrial fibrillation (AF) and to assess the effective use of warfarin anticoagulation in this group A retrospective study of patients admitted with stroke or transient ischaemic attack (TIA) to Whangarei Hospital between 1 Jan 2010 and 1 Sept 2010. Of 198 stroke/TIA patients identified, 47 (24%) had confirmed persistent or paroxysmal AF (PAF) or flutter. Only 12 (31%) patients with pre existing PAF or AF were on warfarin and only 1 patient had an ischaemic stroke while in the therapeutic INR range of 2.0-3.0. The commonest reason cited for no anticoagulation was patients' wishes. In our region, effective warfarin use for stroke prevention in AF patients is lower than recommended. This may be improved with increased awareness of efficacy and safety of warfarin and more thorough monitoring of INR.


A bibliometric study of Revista Española de Enfermedades Digestivas (REED) based on SciELO indicators for the period 2004-2018.
The aim of this study was to show the potentialities offered by the SciELO network indicators for the management of scientific journals, via a case study involving the Revista Española de Enfermedades Digestivas (REED). SciELO offers indicators (production, collaboration, use) that complement the conventional analysis indices used for written science. In order to illustrate their use as a bibliometric, a descriptive study was performed of the scientific production published by the above-mentioned journals during the period 2004-2018. In the last five years, REED received 3,976,685 visits. The second issue from 2007 was the most widely accessed sample to date. A total of 173 issues, 1,810 citable articles, 2,927 documents and 47,645 references have been published, with the number of published papers increasing by 268 %. Clinical case reports make up the highest number. REED received a total of 3,613 citations, with a self-citation rate of 60 %. Of all published documents, 42 % originated in Spain and 10.6 % abroad. Group authorship predominates over individual authors, with a median and mode of 5. The cooperation index was 5.12. The highest impact factor was 0.492 in 2008. The journals most commonly cited by REED are all foreign publications in the Gastroenterology and Hepatology section of the Science Citation Index.


Serial changes of the susceptibility of epileptogenic focus during hippocampal kindling induced with low-frequency electrical stimulation in cats.
Cats were stimulated in the dorsal hippocampus with low-frequency square wave pulses. All subjects were kindled until generalized convulsion occurred. In the early stage of the kindling process, an increase in the interpulse interval and a decrease in the number of stimulating pulses required for the provocation of epileptic afterdischarge were observed, but in the late stage a decrease in the former and an increase in the latter were observed. It appears from these data that completion of hippocampal kindling is accompanied by a decrease in excitability at the site of stimulation subsequent to an increase in the same.


Effects of organic pollutants on struvite crystallization kinetics and the molecular mechanism of inhibition on crystal growth.
The abilities of improving phosphorus (P) resources sustainability and reducing water eutrophication make struvite crystallization technology attract increasing interest in wastewater treatment, but struvite crystallization process may be affected by various impurities in wastewater. In this study, the effects of nine representative ionic surfactants including three types (anionic, cationic and zwitterionic) on crystallization kinetics and product quality of struvite were investigated, and the influencing mechanism was further probed. The results demonstrated that anionic surfactants significantly inhibit crystal growth so as to reduce crystal size especially in a-axis direction, change crystal morphology and decrease P recovery efficiency, and also lead to a slight decline in product purity. In contrast, cationic and zwitterionic surfactants have no obvious influence on the formation of struvite. A series of experimental characterizations and molecular simulations collectively revealed that the inhibition of crystal growth by anionic surfactants is attributed to the adsorption of anionic surfactant molecules on struvite crystal surface and subsequent blockage of active growth sites. The binding ability of surfactant molecules with the Mg2+ exposed on struvite crystal surface was highlighted to be the most essential factor determining the adsorption behavior and adsorption capacity. Anionic surfactants with stronger binding ability with Mg2+ have more intense inhibitory effect, but a large molecular volume of anionic surfactants will weaken the adsorption capacity on crystal surface so as to reduce the inhibitory effect. Contrastively, cationic and zwitterion surfactants without binding ability with Mg2+ have no inhibitory effect. These findings enable us to have a clearer understanding of the impact of organic pollutants on struvite crystallization and make a preliminary judgment on the organic pollutants that may have the ability to inhibit the crystal growth of struvite.


Opioid receptor changes in weaver mouse striatum.
The dopaminergic projection from the substantia nigra to the patch and matrix compartments of the caudate-putamen undergoes a spontaneous, early postnatal degeneration in mice which carry the weaver gene. The projection to nucleus accumbens is relatively spared. Dopaminergic afferents have been shown to be important modulators of striatal opioid receptor expression. In the present study, opioid receptor localization in the caudate-putamen and nucleus accumbens of control and weaver mice was examined by quantitative autoradiography. Mu, delta and kappa opioid receptors were differentially distributed in nucleus accumbens and in patch and matrix compartments of the caudate-putamen. In animals which were homozygous for the weaver gene, the density of mu opioid receptors in both patch and matrix compartments was unchanged with respect to control mice. In contrast, the density of delta and kappa opioid receptors was significantly decreased in weaver caudate-putamen and nucleus accumbens. The significance of these results with respect to opioid receptor expression and Parkinson's disease is discussed.


Chronic treatment of exendin-4 affects cell proliferation and neuroblast differentiation in the adult mouse hippocampal dentate gyrus.
Exendin-4 isolated from Heloderma suspectum venom acts via glucagon-like peptide 1 (GLP-1) receptor and has clinically been used in the type 2 diabetes. In this study, we investigated the effects of exendin-4 on cell proliferation and neuroblast differentiation in the subgranular zone (SGZ) of the dentate gyrus in mice. Exendin-4 was treated intraperitoneally to male ICR mice twice a day for 21 days. The exendin-4-treated group showed a significantly higher number of Ki67- (1.51-fold), doublecortin (DCX)- (2.5-fold) and 5-bromo-2'-deoxyuridine (BrdU)+DCX- (2.46-fold) immunoreactive cells in the SGZ of the dentate gyrus compared to the control group. The results of this study showed that treatment with exendin-4 increased cell proliferation neuroblast differentiation in the SGZ of the dentate gyrus, suggesting that exendin-4 promotes structural plasticity in the dentate gyrus.


Sympathetic response to stimulation of the pontine A5 region in conscious rabbits.
Studies in anaesthetized animals have shown that the pontine A5 noradrenergic region plays an important role in the sympathetic control of arterial pressure (AP). The aim of this study was to develop, in conscious rabbits, a technique for microinjections into the A5 region and examine the effects of stimulation of this region on renal sympathetic nerve activity (RSNA). In preliminary mapping experiments on four anaesthetized rabbits, electrical stimulation of the A5 region induced a pressor response ranging between 25 and 75 mmHg while unilateral injection of glutamate (100 nmol) did not change AP. The mapping experiments were used to enable guide cannulae implantation for subsequent microinjections into the A5 region. In six conscious rabbits, unilateral injection of glutamate (100 nmol) caused a consistent increase in RSNA (+45%) but did not change AP. In another eight rabbits, bilateral injection of glutamate (0.3, 3, 30 nmol) into the A5 region dose-dependently increased RSNA by 13%, 30% and 40%, respectively. In four rabbits, angiotensin II (0.3, 3, 30 pmol) injected bilaterally into the A5 region increased RSNA by 5%, 22% and 28%, respectively. In all animals the increase in RSNA was mainly mediated by increasing amplitude of sympathetic synchronized bursts while their frequency remained unchanged. However, both glutamate and angiotensin II did not change AP indicating that the sympathoexcitatory response to the A5 stimulation might be relatively confined to the renal bed. Using a novel microinjection technique developed for conscious rabbits, we found that the A5 region may provide an important excitatory and possibly selective input to the renal sympathetic preganglionic neurons.


Plasmacytoma of the ovary.
A plasmacytoma of the ovary in a 63-year-old is described. It was associated with an IgA K paraprotein. Myelomatosis developed 2 years after excision of the tumor.


Intersexuality in aquatic invertebrates: Prevalence and causes.
This review is the first assembling information on intersexuality in aquatic invertebrates, from freshwater to estuarine and marine environments. Intersex is a condition whereby an individual of a gonochorist (separate sexes) species has oocytes or distinct stages of spermatogonia, at varying degrees of development, within the normal gonad of the opposite gender (i.e. spermatocytes in the ovary or oocytes in the testis), often involving alterations in the gonadal structure, reproductive tract or external genitalia. By the end of 2016 we found approximately 340 records of aquatic invertebrate species evidencing signs of intersexuality (or imposex), all comprised within the Phyla Mollusca and Arthropoda. Gastropod molluscs are by far the group with more examples documented (256 species), followed by crustaceans, i.e., decapods, copepods and amphipods. To our knowledge no further cases of intersexuality were known concerning other invertebrate taxa. Despite some reports suggesting that a baseline level of intersexuality may occur naturally in some populations, the causes are multifaceted and mostly linked with environmental contamination by estrogenic and organotin endocrine disrupting chemicals (EDCs), parasitism, and genetic/environmental sex determination abnormalities. A more comprehensive discussion about the origin of intersexuality, prevalence and causes, knowledge gaps and future research directions in the light of new omics scientific advances (genomics, proteomics and transcriptomics) is also provided. The lack of studies linking molecular responses of invertebrate intersex individuals to multiple stressors represents a true challenge to be further investigated in the future.


Mechanisms of action of the antidepressants fluoxetine and the substance P antagonist L-000760735 are associated with altered neurofilaments and synaptic remodeling.
Antidepressants are widely prescribed in the treatment of depression, although the mechanism of how they exert their therapeutic effects is poorly understood. To shed further light on their mode of action, we have attempted to identify a common proteomic signature in guinea pig brains after chronic treatment with two different antidepressants. Both fluoxetine and the substance P receptor (NK(1)R) antagonist (SPA) L-000760735 altered cortical expression of multiple heat shock protein 60 forms along with neurofilaments and related proteins that are critical determinants of synaptic structure and function. Analysis of NK(1)R-/- mice showed similar alterations of neurofilaments confirming the specificity of the effects observed with chronic NK(1)R antagonist treatment. To determine if these changes were associated with structural modification of synapses, we carried out electron microscopic analysis of cerebral cortices from fluoxetine-treated guinea pigs. This showed an increase in the percentage of synapses with split postsynaptic densities (PSDs), a phenomenon that is characteristic of activity-dependent synaptic rearrangement. These findings suggest that cortical alterations of the neurofilament pathway and increased synaptic remodeling are associated with the mechanism of these two antidepressant drug treatments and may contribute to their psychotherapeutic actions.


In rats, sighs correlate with relief.
A deep breath, i.e., a sigh, in mammals is a ubiquitous respiratory phenomenon, whose function is to prevent airlessness (atelectasis) in hypoventilated parts of lungs. Sighs are also correlated with emotions, such as anxiety, anger and resentment in humans and obviously, judging from the expression--sigh of relief--in many languages, with relaxation or relief. If sighs are indiscriminately associated with opposite emotions, their role in social communication is doubtful. If, however, there is a selective facilitation of sighs by either fear, anxiety or relief, then they might, in addition to their respiratory role, function also as a social signal of a particular mood. To induce fear a stimulus was paired with a tail shock (5 times in a daily session). To provide a relief, another stimulus, presented before the expected shock (also 5 times per session), was followed by the omission of shock. In 16 rats experiencing fear during a Danger Stimulus (predictor of tail shock) and a relief during the Safety Stimulus (predictor of the non-occurrence of expected shock) the rate of sighing was 7.5 times higher during relief (180/h) than during fear (24/h), and 20 times higher than between trials (9/h), with all differences highly significant (p<0.001). This clear correlation of sighs with relief (from fear of the tail shock) supports our hypothesis that sighs in social mammals may function as signals of safety.


Cross-cultural translation, reliability and validity of the Thai version of the Patient‑Reported Outcomes Measurement Information System (PROMIS) Parent Proxy Upper Extremity Short Form 8a in children with congenital upper extremity anomalies.
The PROMIS Parent Proxy Upper Extremity Short Form 8a version 2 (PROMIS Parent Proxy UE-SF) is one of the most commonly used self-assessment questionnaires for evaluating function in children with congenital upper extremity anomalies. However, this English questionnaire is difficult for Thai parents to complete. The purpose of this study is to translate the PROMIS Parent Proxy UE-SF into Thai and test its reliability and validity. The PROMIS Parent Proxy UE-SF was translated into Thai using FACIT translation methodology. This version and the Thai version of the Michigan Hand Questionnaire (Thai-MHQ) were used to evaluate 30 Thai children with different types of congenital upper extremity anomalies. The reliability and validity of the Thai-PROMIS Parent Proxy UE-SF were evaluated by test-and-retest with the intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient. Correlations between the Thai-PROMIS Parent Proxy UE-SF and Thai-MHQ were analysed by Pearson's correlation coefficients. The children's mean age was 4.47 ± 2.08 years (range 1-9 years). The main diagnoses included thumb duplication (11 children), syndactyly (4 children)4, congenital trigger thumb (3 children) and obstetric brachial plexus palsy (3 children). The children's parents completed the questionnaires, taking 164.23 ± 22.58 s for the Thai-PROMIS and 337.8 ± 49.37 s for the Thai-MHQ. The test-retest reliability of Thai-PROMIS evaluated by ICCs, was 0.9909 (good reliability), and the Cronbach's alpha of all items was 0.923. The Pearson's correlation coefficient between the Thai-PROMIS and Thai-MHQ showed a strong correlation with Domain 2 (activities of daily living, r = 0.7432) and a moderate correlation with the overall Thai-MHQ score (r = 0.699). The Thai-PROMIS Parent Proxy UE-SF is a valid, reliable and easy-to-use patient-reported outcome measure for assessing function in children with congenital upper extremity anomalies.


Can surgical weight loss reduce the risk of developing coronary heart disease?
Coronary heart disease (CHD) accounts for one third of all deaths in people older than 35 years in the United States. The aim of this study is to determine the impact of bariatric surgery, especially laparoscopic sleeve gastrectomy, on the risk of developing CHD. Academic, University affiliated hospital. We retrospectively reviewed all patients who underwent bariatric surgery from 2010-2016. All patients between 30 and 74 years of age without a previous history of CHD were included in our study. The risk score for predicting the incidence of CHD was measured preoperatively and at 12 months of follow-up. Of the 1330 patients studied, 225 patients (16.9%) had all the required variables to calculate the CHD risk score. The mean age of our population was 51.4 ± 11.3 years, mostly female (67%, n = 152) and white (58.7%, n = 132). At the preoperative setting, our patient population had a systolic blood pressure in the prehypertensive ranges, with 40% (n = 90) having type 2 diabetes and 60% (n = 134) having arterial hypertension. The preoperative CHD preoperative risk was 8.9 ± 7.7% or 8-fold higher than the ideal risk. After 12 months of follow-up, the CHD absolute risk reduction was 2.7%, and the relative risk reduction was 42.0% for female patients and 5.4% and 38.8%, respectively, for male patients. All the metabolic factors used to calculate the risk of developing CHD had a significant improvement after 12 months. Surgical weight loss reduces the risk of developing CHD. Further studies should assess these findings in a long-term follow-up.


A qualitative investigation of Johnson's typology.
The couple typology described by Johnson and Ferraro (2000) provided the framework for this analysis of narrative accounts of couples in violent heterosexual relationships. Participants were 15 bidirectionally violent couples who were interviewed separately for about 1 hour each. Modified analytic induction guided the analyses. We categorized the violence in the relationships of these 15 couples in the following ways: 11 were categorized as "common couple" violence; two as "violent resistance"; one as "mutual violent control"; and one couple was categorized as what we named "pseudo-intimate terrorism." We present rich descriptions of each category and motivations for and impacts of aggressive behavior as well as our rationale for classifying couples the way we did. Implications for intervention and future research are discussed.


Effects of Lactobacillus casei Strain T2 (IBRC-M10783) on the Modulation of Th17/Treg and Evaluation of miR-155, miR-25, and IDO-1 Expression in a Cuprizone-Induced C57BL/6 Mouse Model of Demyelination.
Multiple sclerosis (MS) is a complex inflammatory disease in which demyelination occurs in the central nervous system affecting approximately 2.5 million people worldwide. Recent reports have shown that the gut microbiome plays a crucial role in the functioning of the immune system in inflammatory diseases such as MS. In this study, the cuprizone-induced demyelination mouse model was used to investigate the effect of Lactobacillus casei strain T2 (IBRC-M10783) on the alleviation of these mice. Female C57BL/6 mice (8-10 weeks old) were divided into 6 groups: group 1, normal control; group 2, cuprizone control (oral administration of cuprizone 0.2% w/w for 4 weeks); group 3, probiotic control (oral administration of 1 × 109 CFU/ml probiotic for 4 weeks); group 4, treatment 1 (probiotic for 4 weeks then cuprizone for 4 weeks); group 5, treatment 2 (cuprizone for 4 weeks then probiotic for 4 weeks); and group 6, treatment 3 (cuprizone for 4 weeks then probiotic for 4 weeks with vitamin D3 at a dose of 20 IU/day). Then, TGF-β and IL-17 were measured by ELISA, and the expression of miR-155, miR-25, and IDO-1 was evaluated by real-time PCR. Among the measured microRNAs, the results showed that there was a significant decrease in miR-155 expression between the treatment 1 group and the cuprizone group. In the case of IL-17, the results also showed a significant reduction between the three treatment groups and the cuprizone group. These observations suggest that L. casei can reduce proinflammatory cytokines and reduce demyelinating symptoms in the mouse model.


A transcriptomic study of Williams-Beuren syndrome associated genes in mouse embryonic stem cells.
Williams-Beuren syndrome (WBS) is a relatively rare disease caused by the deletion of 1.5 to 1.8 Mb on chromosome 7 which contains approximately 28 genes. This multisystem disorder is mainly characterized by supravalvular aortic stenosis, mental retardation, and distinctive facial features. We generated mouse embryonic stem (ES) cells clones expressing each of the 4 human WBS genes (WBSCR1, GTF2I, GTF2IRD1 and GTF2IRD2) found in the specific delated region 7q11.23 causative of the WBS. We generated at least three stable clones for each gene with stable integration in the ROSA26 locus of a tetracycline-inducible upstream of the coding sequence of the genet tagged with a 3xFLAG epitope. Three clones for each gene were transcriptionally profiled in inducing versus non-inducing conditions for a total of 24 profiles. This small collection of human WBS-ES cell clones represents a resource to facilitate the study of the function of these genes during differentiation.


Relationship between central sympathetic activity and stages of human hypertension.
The magnitude of sympathetic hyperactivity in essential hypertension (EHT) varies with its severity and complications. There are no data on sympathetic nerve activity in borderline (BHT) or white-coat hypertension (WHT) relative to the various stages of EHT, despite suggestions that both lead to established EHT and organ damage through sympathetic mechanisms. We planned to determine the magnitude of sympathetic nerve activity in patients with BHT and WHT in relation to normality and various stages of sustained EHT. We examined 90 untreated subjects comprising matched groups with BHT (n = 13), WHT (n = 12), Sixth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure EHT stage 1 (EHT-1 n = 12), EHT stages 2 and 3 (EHT-2/3 n = 14), high-normal pressure (HN n = 14), and normal pressure (NT n = 13), as well as a group with EHT complicated by left ventricular hypertrophy (EHT+LVH n = 12). We quantified muscle sympathetic nerve activity as the mean frequency of multiunit discharge (MSNA) and that of single-units (s-MSNA). We found a greater (at least P <.01) mean central sympathetic frequency in BHT (75 +/- 5.8 impulses/100 beats), EHT-1 (76 +/- 4.0 impulses/100 beats), and EHT+LVH (79 +/- 4.3 impulses/100 beats) than in EHT-2/3 (57 +/- 3.1 impulses/100 beats), WHT (52 +/- 3.6 impulses/100 beats), HN (42 +/- 3.9 impulses/100 beats), and NT (33 +/- 3.6 impulses/100 beats). BHT hyperactivity was closer to that of EHT, whereas WHT was closer to NT. Central sympathetic activity was greatest in BHT, early stage, and complicated EHT, and as such is likely to play an integral role in the development of hypertension and its complications. Sympathetic hyperactivity occurs in WHT, but to a lesser extent than in BHT.


Cytotoxic diterpenoids from Rabdosia lophanthoides var. gerardianus.
Two new abietane diterpenoids, Gerardianin B (1) and Gerardianin C (2), one new lignan glycoside, Gerardianin D (3) and one new lupane-type triterpenoid, Gerardianol A (4), together with seven known abietane diterpenoids were isolated from the aerial parts of Rabdosia lophanthoides var. gerardianus. Their structures were determined by 1D and 2D NMR spectroscopic data. The cytotoxic activities of the nine diterpenoids were evaluated on human cancer cell lines. Compounds 6-11 exhibited significant cytotoxic activities against HepG2 cell lines with IC50 from 4.68 to 9.43μM and HCF-8 cell lines with IC50 from 9.12 to 13.53μM.


Endoscopy versus double-contrast barium enema in the evaluation of patients with symptoms suggestive of colorectal carcinoma.
Two hundred seventy-six patients with positive findings on a stool guaiac test, hematochezia, a change in bowel habits, or a family history of colorectal carcinoma were referred to the colorectal clinic for further investigation. There were 105 men and 171 women. All patients underwent examination with the 65 cm flexible sigmoidoscope. Patients with no abnormalities on endoscopy underwent a double-contrast barium enema. If the barium enema revealed a polyp or other suspicious pathologic process, the patient was referred for colonoscopy. In 258 patients, findings of barium enema and flexible sigmoidoscopy were in agreement. The findings in 178 of these examinations were completely negative, and in the remaining 80 cases flexible endoscopy and barium enema revealed diverticulosis. In an additional 18 patients, negative findings on flexible sigmoidoscopy were followed by positive findings on barium enema. Thirteen of these 18 patients (72 percent) had negative findings on colonoscopies and therefore had false-positive findings on barium enema. In the remaining five patients (28 percent), an unsuspected colonic carcinoma or premalignant polyp was discovered on barium enema and documented by colonoscopy. Also, in four of these five patients, colonoscopy found additional polyps that were not seen on barium enema.


Influence of sulfide concentration on the corrosion behavior of titanium in a simulated oral environment.
This study assessed the corrosion behavior of titanium in response to sulfide by determining the effects of sulfide concentration and pH over immersion period. Corrosion was evaluated through changes in color, glossiness, surface characterization, and titanium release. Sulfide solutions were prepared in 3 different concentrations with Na2S, each in pH unadjusted (sulfide-alkaline) and pH adjusted to 7.5 (sulfide-neutral). Titanium discoloration increased and glossiness decreased as sulfide concentration and immersion period increased in sulfide-alkaline solutions. Coral-like complexes were observed on the surface of these specimens, which became more pronounced as concentration increased. Small amounts of titanium release were detected in sulfide-alkaline solutions; however, this was not affected by immersion periods. Corrosion was indicated through considerable surface oxidation suggesting the formation of a thick oxide layer. No significant changes in color and glossiness, or titanium release were indicated for titanium specimens immersed in sulfide-neutral solutions indicating that pH had a significant effect on corrosion. Our findings suggest that a thick oxide layer on the titanium surface was formed in sulfide-alkaline solutions due to excessive oxidation.


Association of potentially functional genetic variants of PLCE1 with gallbladder cancer susceptibility in north Indian population.
Phospholipase C epsilon 1 (PLCE1) plays crucial roles in carcinogenesis and progression of esophageal and gastric cancers. In the present study, we investigated association of GWAS identified rs2274223 A>G and. rs7922612 T>C polymorphism of PLCE1 with susceptibility to gallbladder cancer (GBC). The study involved genotyping of selected PLCE1 variants in 416 GBC cases and 225 controls. Haplotype analysis was done by SNPStats. In silico analyses were performed using bioinformatic tools. PLCE1 rs2274223 [AG] and rs7922612 [CC] genotypes were found to be significantly associated with an increased risk of GBC [OR = 1.9, p = 0.002; OR = 2.0, p = 0.04, respectively]. PLCE1 haplotype [Grs2274223-Crs7922612] also showed significant association with GBC [OR = 1.8, p = 0.04]. The association was significant in females and GBC patients with stones and female GBC patients with gallstones [OR = 2.6, p = 0.01; OR = 3.3, p = 0.007], respectively. However, no significant associations with other risk factors such as tobacco usage and age of onset were found. Functional prediction of rs2274223 A>G suggested change in protein coding and splicing regulation. The present study found a significant association of PLCE1 rs2274223 and rs7922612 polymorphisms with susceptibility to GBC probably through gallstone-mediated inflammatory pathway.


Fibrinopeptide A and beta thromboglobulin in patients with angina pectoris and acute myocardial infarction.
The purpose of this study was to investigate the degree of platelet activation and thrombin generation in 40 patients with stable angina pectoris and in 20 patients with acute myocardial infarction (AMI) by determining the plasma beta thromboglobulin (BTG) and fibrinopeptide A (FPA) concentrations. In patients with angina pectoris increased platelet activation correlated with extensive coronary pathology; the activation, however, was not influenced by a previous myocardial infarction, use of oral anticoagulants, beta-blocking agents, or hyperlipidemia. The plasma beta thromboglobulin concentration predicted more accurately the extent of the coronary artery disease than the functional angina pectoris classification. Thrombin generation was within the normal range. In patients with acute myocardial infarction increased platelet activation and enhanced thrombin generation were found, which were not related to the infarct localization, infarct size, or the presence of complications. Consequently, in these patients determination of plasma beta thromboglobulin and fibrinopeptide A concentrations is useless for the diagnosis of venous thromboembolism.


Does reduction mammaplasty revert skeletal disturbances in the vertebral column of patients with macromastia? A preliminary study.
Enlarged breasts are associated with many physical and psychological symptoms. It is important to use objective criteria in documenting physical changes of a patient's body due to enlarged breasts and the benefits of surgery. This preliminary study aimed to determine whether the reduction mammaplasty procedure changes the angles of cervical lordosis, thoracic kyphosis, and lumbar lordosis. The study population consisted of 22 patients who underwent breast reduction surgery. All the patients had lateral cervicothoracolumbar radiographs taken preoperatively and at least 2 months postoperatively. Cervical lordosis, thoracic kyphosis, and lumbar lordosis angles, as well as sagittal balance, were examined. The body mass index (BMI), breast tissue volume, and excised tissue amount of each patient were recorded. All the patients had increased cervical lordosis and thoracic kyphosis angles preoperatively, and the angles were significantly decreased postoperatively. Of the 22 patients, 7 had decreased and 8 had increased lumbar lordosis angles. All the lordosis angles showed significant improvement at the last examination. Seven patients had disturbed sagittal balance preoperatively, and all had normal sagittal balance postoperatively. Preoperative total breast tissue volume was positively correlated with the differences in cervical lordosis angles, BMI, preoperative cervical lordosis angles, and cervical lordosis angles. Hypertrophic breasts are not only a cosmetic but also a functional problem complicated by pathologic conditions in the vertebral column such as increased cervical lordosis, thoracic kyphosis, and increased or decreased lumbar lordosis. Breast reduction may improve these pathologic angles. Reducing the nonphysiologic weight of enlarged breasts located anterior to the main axis of the body may correct pathologic angulation and disturbed sagittal balance of the vertebral column. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Pain-relevant responses from significant others: development of a significant-other version of the WHYMPI scales.
This paper reports on the development of a measure of significant-others' reports of the frequency of their solicitous, distracting and negative responses to chronic pain patients demonstrations of pain. This significant-other version is based on analogous scales that comprise part of the West Haven-Yale Multidimensional Pain Inventory (WHYMPI). The 3 pain-relevant response scales were demonstrated to have adequate indices of internal consistency and criterion-related validity. The potential clinical and research utility of the measure is discussed.


Iron stores in low and normal birth weight infants at birth and in early infancy.
Serum ferritin levels of low birth weight (LBW; BW < 2,500 g) and normal birth weight (NBW; BW ≥ 2,500 g) infants were evaluated at birth and at 3 mo using electrochemiluminescence immunoassay. At birth, levels were 318.6 (31.0-829.5) ng/mL in LBW (n = 217) and 366.2 (122.4-858.5) ng/mL in NBW infants (n = 116; p < 0.01), with 1.4 % of LBW and none of the NBW infants having levels <12 ng/mL (p = 0.20). At follow up, levels were 66.9 (4.5-567.7) ng/mL in LBW (n = 126) and 126.2 (6.8-553.7) ng/mL in NBW infants (n = 76; p = 0.27), with 11.9 % of LBW and 11.8 % of NBW infants having levels <12 ng/mL (p = 0.80).


A machine-learning approach to human ex vivo lung perfusion predicts transplantation outcomes and promotes organ utilization.
Ex vivo lung perfusion (EVLP) is a data-intensive platform used for the assessment of isolated lungs outside the body for transplantation; however, the integration of artificial intelligence to rapidly interpret the large constellation of clinical data generated during ex vivo assessment remains an unmet need. We developed a machine-learning model, termed InsighTx, to predict post-transplant outcomes using n = 725 EVLP cases. InsighTx model AUROC (area under the receiver operating characteristic curve) was 79 ± 3%, 75 ± 4%, and 85 ± 3% in training and independent test datasets, respectively. Excellent performance was observed in predicting unsuitable lungs for transplantation (AUROC: 90 ± 4%) and transplants with good outcomes (AUROC: 80 ± 4%). In a retrospective and blinded implementation study by EVLP specialists at our institution, InsighTx increased the likelihood of transplanting suitable donor lungs [odds ratio=13; 95% CI:4-45] and decreased the likelihood of transplanting unsuitable donor lungs [odds ratio=0.4; 95%CI:0.16-0.98]. Herein, we provide strong rationale for the adoption of machine-learning algorithms to optimize EVLP assessments and show that InsighTx could potentially lead to a safe increase in transplantation rates.


The functions of Ca(2+) in bacteria: a role for EF-hand proteins?
In bacteria, Ca(2+) is implicated in a wide variety of cellular processes, including the cell cycle and cell division. Dedicated influx and efflux systems tightly control the low cytoplasmic Ca(2+) levels in prokaryotes. Additionally, the growing number of proteins containing various Ca(2+)-binding motifs supports the importance of Ca(2+), which controls various protein functions by affecting protein stability, enzymatic activity or signal transduction. The existence of calmodulin-like proteins (containing EF-hand motifs) in bacteria is a long-standing hypothesis. Analysis of the prokaryotic protein sequences available in the databases has revealed the presence of several calmodulin-like proteins containing two or more authentic EF-hand motifs, suggesting that calmodulin-like proteins could be involved in Ca(2+) regulation in bacteria.


Safety and tolerability of intranasal cocaine during phendimetrazine maintenance.
Phendimetrazine appears to have limited abuse potential and reduces cocaine self-administration in preclinical studies. No human studies have evaluated the safety and tolerability of cocaine in combination with phendimetrazine, which is a necessary next step in evaluating the efficacy of phendimetrazine for treating cocaine use disorder. This study determined the safety and tolerability of acute cocaine doses during chronic phendimetrazine treatment. Ten subjects completed this within-subject, placebo-controlled, inpatient study. Subjects were maintained on ascending oral phendimetrazine doses (0, 70, 140, and 210 mg/day). After at least seven maintenance days at each dose, subjects received ascending doses of intranasal cocaine (0, 10, 20, 40, and 80 mg), separated by 90 min, within one session. Cocaine produced prototypical cardiovascular and subject-rated effects (e.g., increased blood pressure and ratings of like drug). The cardiovascular effects of cocaine alone were not clinically significant for an acute drug response (e.g., average heart rate did not approach tachycardia, 100 beats/min). Phendimetrazine enhanced peak heart rate following placebo and low cocaine doses, but these effects were also not clinically significant. Phendimetrazine was otherwise devoid of effects alone and did not alter the subject-rated effects of cocaine or hypothetical demand for cocaine on a purchase task. Cocaine was safe and well tolerated during maintenance on a threefold range of phendimetrazine doses. Given this safety profile, the reduced abuse potential of phendimetrazine and promising preclinical research, future human laboratory studies, and possibly clinical trials should evaluate the efficacy of phendimetrazine for reducing cocaine use.


Antibody-dependent cell-mediated cytotoxicity using a murine monoclonal antibody against human colorectal cancer in cancer patients.
Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by a murine monoclonal antibody against human colorectal carcinoma, antibody 19-9, with human effector cells was tested in 33 patients with various carcinomas, 16 patients with benign lesions, and 13 normal controls, using a 12-h 51Cr release assay using human colorectal cancer cells as targets. Peripheral blood mononuclear cells (PBM) from these groups of patients and normal controls achieved moderate levels of target cell lysis in the presence of the monoclonal antibody at the high effector to target cell ratio of 200:1. The ADCC activity of PBM in cancer patients was significantly higher than that in either normal persons or patients with benign lesions. Since the ADCC was shown to be mainly mediated by adherent monocytes in the PBM, ADCC activity of monocytes from cancer patients was compared to those from control groups at an effector to target cell ratio of 30:1. The results also showed that the lytic capacity of monocytes was significantly higher in cancer patients than that in the control populations.


Ab initioscreening of two-dimensional CuQxand AgQxchalcogenides.
Two-dimensional (2D) chalcogenides have attracted great interest from the scientific community due to their intrinsic physical-chemical properties, which are suitable for several technological applications. However, most of the reported studies focused on particular compounds and composition, e.g., MoS2, MoSe2, WS2, and WSe2. Thus, there is an increased interest to extend our knowledge on 2D chalcogenides. Here, we report a density functional theory (DFT) screening of 2D coinage-metal chalcogenides (MQx), whereM= Cu, Ag,Q= S, Se, Te,x= 0.5, 1.0, 1.5, 2.0, with the aim to improve our atomistic understanding of the physical-chemical properties as a function of cation (M), anion (Q), and composition (x). Based on 258 DFT calculations, we selected a set of 22 stableMQxmonolayers based on phonons analyses, where we identified 9 semiconductors (7 AgQxand 2 CuQx), with band gaps from 0.07 eV up to 1.67 eV, while the remaining systems have a metallic character. Using all 258 systems, we found a logarithmic correlation between the average weighted bond lengths and effective coordination number of cations and anions. As expected, the monolayer cohesive energies increase with the radius of theQspecies (i.e., from S to Te). Furthermore, an increase in the anion size diminishes the work function for nearly allMQxmonolayers, which can be explained by the nature of the electronic states at the valence band maximum.


Theoretical studies on the related properties of Co(III) polypyridyl complexes interacting with DNA.
Theoretical studies on the related properties of Co(III) polypyridyl complexes [Co(phen)(2)L](3+) (L: dppz = dipyrido[3,2-a:2',3'-c]phenazine; phen = 1,10-phenanthroline; dione = 1,10-phenanthroline-5,6-diketone) 1-3 interacting with DNA, including the DNA-binding, DNA-photocleavage and spectral properties, have been carried out. First, the full geometry-optimizations of these three complexes in their ground states were carried out in aqueous solution. The optimized structures of these three complexes were docked into DNA-base-pairs using the Dock6.0 program. Secondly, the binding modes of complexes 1-3 were revealed in detail and the trend in DNA-binding affinities was reasonably explained. Thirdly, the electronic absorption and emission spectra of docking model of the optimal complex 1 were calculated and simulated. The experimental intense absorption and emission bands of Co(Ш) complex 1 in the presence of DNA were explained in detail, in particular, the reason why the emission spectra of complex 1 in the presence of DNA are greatly stronger than those in the absence of DNA was theoretically elucidated. Finally, the DNA-photocleavage essential of complexes was explored and the DNA photocleavage efficiencies (φ), i.e., φ(1)>φ(2)>φ(3), was also reasonably explained.