Musculocutaneous latissimus dorsi free transfer flap for total phalloplasty in children.
Total phalloplasty is rarely performed in children due to the mutilation involved and the dilemma concerning neophallic size in children. We present a musculocutaneous latissimus dorsi free transfer flap for total phalloplasty in children with difficult psychological problems. Total phalloplasty was performed in eight boys aged between 10 and 15 years. Indications were small penis after failed epispadias repair (4), micropenis (3) and intersexuality (1). A musculocutaneous latissimus dorsi free flap was harvested with thoracodorsal artery, vein and nerve. The flap was transferred to the pubic region and anastomosed to the femoral artery, saphenous vein and ilioinguinal nerve. Two-staged urethroplasty was performed in five patients using buccal mucosa, while in the remaining three a Mitrofanoff channel had been created previously. An inflatable penile prosthesis was implanted in two cases after puberty. Follow-up was from 6 to 53 months (mean: 29 months). Penile size varied from 13 to 16 cm in length and from 10 to 12 cm in circumference. No flap necrosis, either partial or total, was noted. The donor site healed acceptably in four cases while in the remaining four moderate scarring occurred. Function of the penile prostheses is satisfactory. Psychological status is significantly improved in all children. Phalloplasty in childhood is indicated to prevent profound psychological problems related to body dysmorphia. The musculocutaneous latissimus dorsi flap is a possible choice for phalloplasty in children that enables good neophallic size as in adults. We recommend this surgery to be performed before puberty to ensure optimal psychosexual pubertal development.


Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity.
We find that prothymosin alpha (PTalpha) selectively enhances transcriptional activation by the estrogen receptor (ER) but not transcriptional activity of other nuclear hormone receptors. This selectivity for ER is explained by PTalpha interaction not with ER, but with a 37-kDa protein denoted REA, for repressor of estrogen receptor activity, a protein that we have previously shown binds to ER, blocking coactivator binding to ER. We isolated PTalpha, known to be a chromatin-remodeling protein associated with cell proliferation, using REA as bait in a yeast two-hybrid screen with a cDNA library from MCF-7 human breast cancer cells. PTalpha increases the magnitude of ERalpha transcriptional activity three- to fourfold. It shows lesser enhancement of ERbeta transcriptional activity and has no influence on the transcriptional activity of other nuclear hormone receptors (progesterone receptor, glucocorticoid receptor, thyroid hormone receptor, or retinoic acid receptor) or on the basal activity of ERs. In contrast, the steroid receptor coactivator SRC-1 increases transcriptional activity of all of these receptors. Cotransfection of PTalpha or SRC-1 with increasing amounts of REA, as well as competitive glutathione S-transferase pulldown and mammalian two-hybrid studies, show that REA competes with PTalpha (or SRC-1) for regulation of ER transcriptional activity and suppresses the ER stimulation by PTalpha or SRC-1, indicating that REA can function as an anticoactivator in cells. Our data support a model in which PTalpha, which does not interact with ER, selectively enhances the transcriptional activity of the ER but not that of other nuclear receptors by recruiting the repressive REA protein away from ER, thereby allowing effective coactivation of ER with SRC-1 or other coregulators. The ability of PTalpha to directly interact in vitro and in vivo with REA, a selective coregulator of the ER, thereby enabling the interaction of ER with coactivators, appears to explain its ability to selectively enhance ER transcriptional activity. These findings highlight a new role for PTalpha as a coregulator activity-modulating protein that confers receptor specificity. Proteins such as PTalpha represent an additional regulatory component that defines a novel paradigm enabling receptor-selective enhancement of transcriptional activity by coactivators.


Seroprevalence and sources of Toxoplasma infection among indigenous and immigrant pregnant women in Taiwan.
Investigation on seroprevalence and risk factors of Toxoplasma gondii infections among indigenous and immigrant pregnant women in Mid-Taiwan showed that anti Taxoplasma-specific IgG antibody counts were significantly higher in indigenes (40.6%) than in immigrants (18.2%), with an odds ratio of OR=3.34 (95% CI: 1.93-4.80). The titre of Taxoplasma-specific IgG was also significantly higher in indigenes than in immigrants (P<0.001). Differences of living styles for Toxoplasma infection between the two groups were drinking untreated water (OR=2.34, 95% CI: 1.36-4.02), consumption of raw/undercooked meats (OR=10.11 95% CI: 4.92-20.78), especially raw/undercooked pork (P=0.000), or raw/undercooked viscera (OR=9.16, 95% CI: 2.97-27.94), contact with cats (OR=5.69, 95% CI: 2.83-11.47), or soil (OR=2.55 95% CI: 1.72-3.80). Differences of risk factors for Toxoplasma infection in terms of positive IgG in the two groups were consumption of raw/undercooked meats (P=0.005) especially raw/undercooked pork (P=0.004), and contact with cats (P=0.013) or soil (P=0.028). It is concluded that seroprevalence of Toxoplasma infection is higher in indigenous pregnant women and related to their living styles. To prevent congenital toxoplasmosis, health education seems required.


Preoperative prognostic nutritional index associated with anastomotic leakage in colorectal cancer patients after surgery.
Anastomotic leakage (AL) is a severe complication of colorectal cancer (CRC) surgery and is associated with the immune and nutritional status. This study aimed to investigate the role of the prognostic nutritional index (PNI) in AL in CRC patients after surgery. A retrospective case-control study was designed in a single center. The clinicopathological features and preoperative laboratory data of 124 CRC patients and 120 non-cancer patients who underwent surgery were collected and examined. Among the CRC patients, 24 had AL. Nutritional indicators were lower in CRC patients than in non-cancer patients (p < 0.05), but the clinical parameters analysis showed that only metastasis (M) stage, albumin, carcinoembryonic antigen (CEA), CA153, and PNI were associated with AL in CRC after surgery (p < 0.05). Prognostic nutritional index had a moderate predictive value for AL, with an area under the curve (AUC) of 0.625. Using the median value as a cutoff point, a high PNI was associated with a longer survival time in CRC patients (p = 0.033), and AL showed marginal significance (p = 0.048). The nomogram showed that PNI has a better prognostic value than tumor-node-metastasis (TNM) staging in CRC patients who underwent surgery. Prognostic nutritional index is a useful supplement for predicting AL in CRC patients after colorectal surgery. It also helps predict the prognosis of CRC patients.


Absence of lipid gel-phase domains in seven mammalian cell lines and in four primary cell types.
Fluorescence properties of 6-lauroyl-2-dimethylaminonaphthalene (Laurdan) are used to explore gel and liquid-crystalline phase domains coexistence in membranes of various cell types and in erythrocyte ghosts. Experiments and simulations were performed using liposomes composed of equimolar gel and liquid-crystalline phases in the absence and in the presence of 30 mol% cholesterol. In this model system two distinct coexisting phases can be easily recognized in the absence of cholesterol. When cholesterol is added to this phospholipid mixture, Laurdan parameters characteristic of the gel and of the liquid-crystalline phase are no longer resolvable. Coexisting domains of gel and liquid-crystalline phase were not detected in any of the examined cell membranes as judged by Laurdan excitation and emission Generalized Polarization (GP) spectra. Both in liposomes and in cell membranes, the behaviour of GP values as a function of excitation and emission wavelength corresponds to a homogeneous liquid-crystalline phase, despite the absolute GP values being relatively high, closer to the values observed in gel phase phospholipids. The presence of cholesterol appears to be the major cause for the homogeneity of phospholipids' dynamical properties in natural membranes, properties that appear close to the liquid-ordered phase state, defined to describe model systems with cholesterol concentration > or = 30 mol%.


Puromycin: two distinct behavioral effects with different temporal parameters in the pigeon.
Pigeons were injected intracerebrally with either puromycin (PM) or control saline solution following training for one 12-min session on a visual discrimination. Injections were made either immediately following training, 1 hr later or 24 hr later. Retention testing 3 days after training showed that PM produced marked amnesia in the first two groups, but had no effect in the 24 hr condition. However, all PM groups were retarded subsequently in the number of days required to reach a 90% discimination criterion. This differentiation of two separate behavioral effects with different temporal gradients suggests that PM may be working through two distinct physiological mechanisms.


Olfactory tests in the diagnosis of essential tremor.
Most patients with tremor-dominant Parkinson's disease (PD) have impaired smell function but it is unclear whether this is true for subjects with essential tremor (ET). If ET patients do not exhibit meaningful smell loss, then olfactory testing may help to distinguish PD from ET. We assessed olfactory function in 59 ET and 64 tremor-dominant PD patients using the University of Pennsylvania Smell Identification Test (UPSIT) and olfactory event-related potential (OERP). UPSIT scores were compared to those from 245 healthy controls, and OERPs were compared to those from 74 controls. Unlike the PD test scores, those of ET patients were indistinguishable from controls when the effects of age, age of onset, gender, and smoking were taken into account. ET patients with a family history of tremor scored significantly better than controls on the UPSIT, and their rate of decline with age was slower. The effect was not observed on OERP. Smell testing may help to distinguish between ET and tremor-predominant PD, and patients with family history of tremor may represent a subgroup whose olfactory function is enhanced by some unknown mechanism.


Effects of cicloxilic acid on bile flow and lipid composition in rats with ethinylestradiol-induced cholestasis.
A subacute dose of ethinylestradiol reduces the bile flow and the bile salt:cholesterol and bile salt + lecithin:cholesterol molar ratios in the rat. An acute dose of cis-2-hydroxy-2-phenyl-cyclohexanecarboxylic acid (cicloxilic acid) 50 mg kg-1 i.v. normalizes these parameters. These findings confirm and extend similar data in laboratory animals and in clinical trials.


Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development.
Transcriptional program that drives human preimplantation development is largely unknown. Here, by using single-cell RNA sequencing of 348 oocytes, zygotes and single blastomeres from 2- to 3-day-old embryos, we provide a detailed analysis of the human preimplantation transcriptome. By quantifying transcript far 5'-ends (TFEs), we include in our analysis transcripts that derive from alternative promoters. We show that 32 and 129 genes are transcribed during the transition from oocyte to four-cell stage and from four- to eight-cell stage, respectively. A number of identified transcripts originates from previously unannotated genes that include the PRD-like homeobox genes ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB and LEUTX. Employing de novo promoter motif extraction on sequences surrounding TFEs, we identify significantly enriched gene regulatory motifs that often overlap with Alu elements. Our high-resolution analysis of the human transcriptome during preimplantation development may have important implications on future studies of human pluripotent stem cells and cell reprograming.


Comparative study of the structure and interaction of the pore helices of the hERG and Kv1.5 potassium channels in model membranes.
The hERG channel is a voltage-gated potassium channel found in cardiomyocytes that contributes to the repolarization of the cell membrane following the cardiac action potential, an important step in the regulation of the cardiac cycle. The lipids surrounding K+ channels have been shown to play a key role in their regulation, with anionic lipids shown to alter gating properties. In this study, we investigate how anionic lipids interact with the pore helix of hERG and compare the results with those from Kv1.5, which possesses a pore helix more typical of K+ channels. Circular dichroism studies of the pore helix secondary structure reveal that the presence of the anionic lipid DMPS within the bilayer results in a slight unfolding of the pore helices from both hERG and Kv1.5, albeit to a lesser extent for Kv1.5. In the presence of anionic lipids, the two pore helices exhibit significantly different interactions with the lipid bilayer. We demonstrate that the pore helix from hERG causes significant perturbation to the order in lipid bicelles, which contrasts with only small changes observed for Kv1.5. These observations suggest that the atypical sequence of the pore helix of hERG may play a key role in determining how anionic lipids influence its gating.


Cotransfer of syntenic human genes into mouse cells using isolated metaphase chromosomes or cellular DNA.
Chromosome-mediated gene transfer (CMGT) of the human genes for hypoxanthine phosphoribosyl transferase (HPRT) and cytosol thymidine kinase (TK1) into HPRT deficient mouse A9 cells or TK deficient Swiss mouse 3T3TK- cells was found to occur at frequencies at least one order of magnitude higher than DNA-mediated gene transfer (DMGT). The frequency of CMGT into 3T3TK- cells was reduced by more than an order of magnitude by a posttreatment of the recipient cells with dimethyl sulphoxide (DMSO). After CMGT, expression of the non-selected genes coding for galactokinase (GALK) and acid alpha-glucosidase (GAA), both syntenic with TK1, was observed in a number of transformants. From the pattern of cotransfer, a tentative gene ordering of CENTROMERE-GALK-TK1-GAA on human chromosome 17 was deduced. Chromosome-mediated cotransfer of X-linked human phosphoglycerate kinase (PGK) with HPRT was observed in two out of 33 A9 transformants analysed. DNA-mediated cotransfer of a syntenic gene was only observed for GALK, cotransferred with TK1 in two out of 18 TK+ transformants of mouse LTK- cells. Therefore, with murine cells as recipients of human donor genetic material, CMGT results in a higher frequency of transfer and a higher incidence of cotransfer of syntenic genes than DMGT using cellular DNA in the same cell system.


Malignant Tenosynovial Giant Cell Tumor: The True "Synovial Sarcoma?" A Clinicopathologic, Immunohistochemical, and Molecular Cytogenetic Study of 10 Cases, Supporting Origin from Synoviocytes.
We present our experience with ten well-characterized malignant tenosynovial giant cell tumors, including detailed immunohistochemical analysis of all cases and molecular cytogenetic study for CSF1 rearrangement in a subset. Cases occurred in 7 M and 3 F (mean age: 52 years; range: 26-72 years), and involved the ankle/foot (n = 1), finger/toe (n = 3), wrist (n = 1), pelvic region (n = 3), leg (n = 1), and thigh (n = 1). There were eight primary and two secondary malignant tenosynovial giant cell tumors. Histologically, all cases showed definite areas of typical tenosynovial giant cell tumor. The malignant areas varied in appearance. In some cases, isolated malignant-appearing large mononuclear cells with high nuclear grade and mitotic activity were identified within otherwise-typical tenosynovial giant cell tumor, as well as forming larger masses of similar-appearing malignant cells. Occasionally, these nodules of malignant large mononuclear cells showed transition to pleomorphic spindle cell sarcoma, with varying degrees of collagenization and myxoid change. One malignant tenosynovial giant cell tumor was composed of sheets of monotonous large mononuclear cells with high nuclear grade, growing in a hyalinized, osteoid-like matrix, with areas of heterologous osteocartilaginous differentiation. Mitotic activity ranged from 2 to 34 mitoses per 10 HPF (mean 18/10 HPF). Geographic necrosis was observed in four cases. The malignant-appearing large mononuclear cells were consistently positive for clusterin and negative for CD163, CD68, and CD11c. Desmin was positive in a small minority of these cells. Areas in malignant tenosynovial giant cell tumor resembling pleomorphic spindle cell sarcoma or osteo/chondrosarcoma showed loss of clusterin expression. RANKL immunohistochemistry was positive in the large mononuclear cells in eight cases. Two cases showed an unbalanced rearrangement of the CSF1 locus. Follow-up (nine patients; range 0.5-66 months; mean 20 months) showed three patients dead of disease, with three other living patients having lung and lymph node metastases; three patients were disease-free. We conclude that malignant tenosynovial giant cell tumors are highly aggressive sarcomas with significant potential for locally destructive growth, distant metastases, and death from disease. The morphologic and immunohistochemical features of these tumors and the presence of CSF1 rearrangements support origin of malignant tenosynovial giant cell tumor from synoviocytes.


Fatty acid modifications during autumnal cold-hardening in an obligatory ectoparasite, the deer ked (Lipoptena cervi).
Poikilothermic organisms often modify their tissue fatty acids (FA) in response to cold exposure by increased unsaturation. In insects, this has been found to be accompanied by increases in the activities or mRNA expression of desaturase enzymes. In the present study, the FA composition of an obligatory ectoparasite, the deer ked (Lipoptena cervi), was analyzed in August-November. In addition to studying the general FA profile of the species, the possible contribution of FA to autumnal cold-hardening was examined. The FA composition of the deer ked imago was relatively similar to previously studied dipteran species, with high percentages of monounsaturated FA (especially 18:1n-9 and 16:1n-7) and 16:0. The individuals caught later in autumn had significantly higher values for the ratio of unsaturated to saturated FA and, regarding individual FA, the percentages of 18:1n-9, 18:2n-6, 18:3n-3, 20:4n-6 and 22:6n-3 were higher but those of 16:0 and 16:1n-7 lower than in August. Potential selective use of particular FA for energy could not account for the large increase in the levels of polyunsaturated FA (PUFA). The observed increased degree of FA unsaturation may have resulted from cold-induced desaturation, as observed previously in other species, or increased survival of the keds with relatively large PUFA contents. The PUFA with low melting points probably allow lipid membranes to maintain sufficient fluidity required to maintain protein functions at low ambient temperatures.


Perturbing pro-survival proteins using quinoxaline derivatives: a structure-activity relationship study.
In HeLa cells the combinatorial knockdown of Bcl-xL and Mcl-1 is sufficient to induce spontaneous apoptosis. Quinoxaline derivatives were screened for the induction of Mcl-1 dependent apoptosis using a cell line without functional Bcl-xL. Quinoxaline urea analog 1 h was able to specifically induce apoptosis in an Mcl-1 dependent manner. We demonstrate that even small changes to 1h results in dramatic loss of activity. In addition, 1 h and ABT-737 synergistically inhibit cell growth and induce apoptosis. Our results also suggest that 1h could have therapeutic potential against ABT-737 refractory cancer.


Design of poly ionic liquids modified cotton fabric with ion species-triggered bidirectional oil-water separation performance.
A novel ion species-responsive oil-water separation material was designed: poly ionic liquid (PIL) was carried on the graphene oxide (GO) by free radical polymerization, then the PIL modified GO sheets (GO-PIL) were coated on cotton fabric (CF). The wettability of the obtained GO-PIL coated CF (GO-PIL@CF) could be switched between hydrophilic and hydrophobic state with the exchange of different types of counteranions. Water contact angle of the GO-PIL@CF could be switched between 0 to about 145°; and correspondingly the underwater oil contact angle would change between about 148 to 0°. Because of the switchable wettability, the GO-PIL@CF could selectively separate water or oil from the oil-water mixtures. Meanwhile, due to the loose fibrous structure, the GO-PIL@CF showed relatively high permeate fluxes; in the hydrophilic state the water flux was about 36000 L/m2h, while in the hydrophobic state the fluxes for the low-density oils (n-hexane and toluene) were about 59,000 and 65000 L/m2h, respectively. Consequently, the separation processes could be completed simply by gravity. In addition, because of the soft and flexible mechanical property, the GO-PIL@CF could serve as wrappage of traditional absorbents and be applied directly as absorbent to remove water or oil selectively from their mixtures.


Leukemic (or stage V) lymphosarcoma.
We have studied 24 cases of secondarily leukemic (stage V) lymphosarcoma (LS), 31 cases of "d'emblée" leukemic LS, and ten cases of lymphoid leukemic neoplasias transitional between "d'emblée" leukemic LS and chronic lymphocytic leukemia (CLL). These cases only concern the common types of the WHO classification of LS, i.e., the prolymphocytic, the lymhoblastic, and the immunoblastic. Some cases have also been classified by cell surface markers. The secondarily leukemic conversion occurred in 40% of the lymphoblastic types, in 14% of the prolymphocytic types, and in 17% of the immunoblastic types. It never occurred at stage I but could occur after any other stage. The mediastinal involvement was observed in three types, but most often in the lymphoblastic type. The prognosis after an acute lymphoid leukemia (ALL) treatment comprising active immunotherapy following chemo(radio)therapy is better for the leukemic prolymphocytic and lymphoblastic LS than for the immunoblastic type. Two patients (one of the lymphoblastic type) are in complete remission after 8 and 5 years, respectively. We have described ten cases of "d'emblée" leukemic LS with either large lymphoid or extra-lymphoid masses, bone marrow leukemic cell involvement, and LS aspects of neoplastic cells. Mediastinal abdominal, or other tumor masses are frequent. The prognosis for "d'emblée" leukemic LS following an ALL treatment is less favorable than ALL prognosis for patients of all ages including children. However, the first remission curve breaks at the 18th month and may form a plateau for about 30% of the patients of all ages. One patient has been in remission for more than 8 years after immunotherapy. We have also described ten cases of lymphoid neoplasia, whose cells cytologically and by the intensity of Ig secretion resemble leukemic prolymphocytic LS cells. However, the disease is more sensitive to CLL treatment than to LS or ALL treatment. Hence, there may be transitional conditions between leukemic LS and CLL. Finally, we have discussed the different possible frontiers between nonleukemic and leukemic LS and proposed two tests to detect the leukemic stage early: the systematic search for LS cells in the peripheral blood after concentration of nucleated cells by centrifugation and for cells carrying immune markers in the isolated mononuclear cell population of peripheral blood and the bone marrow.


Facilitation of ouabain binding to (Na+ + K+)-ATPase by vanadate at in vivo concentrations.
In the presence of Mg2+ vanadate was shown to facilitate ouabain binding to (Na+ + K+)-ATPase in much the same way as Pi does. Thus the hypothesis that vanadate interacts with the phosphate site of the enzyme seems to be supported by ouabain binding experiments. At given ouabain concentrations maximum binding is achieved at microM concentrations of vanadate whereas mM concentrations of Pi are needed. Na+ as well as K+ counteract ouabain binding but some cardiac glycoside binding is still possible at in vivo concentrations of these cations. A minor contamination of the enzyme preparations with vanadate could explain the in vitro binding of ouabain that can be obtained with Mg2+ and in the absence of Pi.


Hand-assisted laparoscopic donor nephrectomy: 1864 cases in 15 years of experience.
To evaluate hand-assisted laparoscopic donor nephrectomy (HALDN) in terms of intraoperative and postoperative results. After institutional review board approval was obtained, a total of 1864 HALDN operations performed between March 2007 and January 2022 were retrospectively analyzed. Age, sex, body mass index (BMI), status of smoking and presence of previous abdominal surgery, laterality, operative time, transfusion requirement, port counts, length of extraction incision, time until mobilization, time until oral intake, donor serum creatinine levels before and one week after the surgery, length of postoperative hospital stay, intraoperative complications, and postoperative recovery and complications were recorded and statistically analyzed. Multiple renal arteries, BMI, right nephrectomy and male sex were also separately evaluated as risk factors for complications and operative time. A total of 825 (44.26%) male and 1039 (55.74%) female patients were enrolled in the study. The mean age of the patients was 45.79 ± 12.88 years. There were a total of 143 complications (7.67% of the total 1864 cases) consisting of 68 (3.65%) intraoperative and 75 (4.02%) postoperative complications. Open conversion was necessary for 10 patients (0.53%) to manage intraoperative complications. Reoperation was needed for 1 patient due to bleeding 6 h after the operation. Multiple renal arteries were a risk factor for intraoperative complications and prolonged operative time. Right nephrectomy and male sex were also related with longer operative times. HALDN is a safe procedure associated with low complication rates.


[Borderline personality disorder in dermatology].
Borderline personality disorder is a syndrome of complex psychopathology which is not very common in dermatology. The emotional symptoms are broad and variable, but typically feature emotional instability, intense anger or lack of control of anger, impulsiveness, instabilities in self-perception, problems at work, chronic feelings of emptiness, unstable partnership relations and recurrent suicidal threats. Self-inflicted injuries are common and may lead patients to dermatologists. A 26-year old woman with borderline personality was hospitalized for neurosyphilis. During inpatient treatment she repeatedly cut herself with razor blades. This article highlights the diagnostic criteria and differential approach of the borderline personality disorder in order to facilitate early recognition and therapy.


Postoperative sense of well-being and quality of life in breast cancer patients do not depend on type of primary surgery.
In primary breast cancer, breast conserving surgery and mastectomy are equal options with regard to patient survival. We therefore investigated whether and how the type of surgery has impact on the patients' quality of life (QoL) in order to support individualized surgical concepts in treatment of breast cancer. 3 types of surgery are compared: breast-conserving surgery; modified radical mastectomy with or without primary reconstruction. 91 out of 114 consecutive patients diagnosed with histologically confirmed primary breast cancer agreed to answer the QoL questionnaires within the first 2 years of their follow-up care. 2 recognized questionnaires on sense of well-being and QoL were used: Multidimensional Mood Questionnaire and QoL SF-12. No significant correlation between sense of well-being and type of operation or tumor stage was found. With regard to health-related QoL, we saw no significant correlation with type of surgery. However, low tumor stage was significantly correlated with better physical (p = 0.012) but not psychological well-being. Within the first 2 years after primary surgery for breast cancer, we did not find significant differences in sense of well-being or QoL dependent on type of surgery.


[Imaging of corneal dystrophies: Correlations between en face anterior segment OCT and in vivo confocal microscopy].
To evaluate the usefulness of en face Optical Coherence Tomography (OCT) for evaluation of corneal dystrophies and to describe correlations with in vivo confocal microscopy (IVCM). Thirty-two eyes of 16 patients with 4 types of corneal dystrophies (epithelial basement membrane dystrophy, Fuchs dystrophy, Reis-Bücklers corneal dystrophy and Crocodile Shagreen dystrophy) were enrolled in this study. Axial and reconstructed en face scans were acquired using OCT. Images were then correlated to IVCM findings. En face OCT provided new insights into the structure, size and depth of corneal tissue alterations in various corneal dystrophies. OCT en face images were well correlated with IVCM features. Despite lower resolution than IVCM, en face OCT offers the advantages of being non-invasive and allowing the analysis of larger corneal areas. En face OCT provides useful new information in corneal dystrophies. This imaging technique will probably increase in popularity in the near future for the assessment of various anterior segment diseases.


Complex ventral hernia repair with a human acellular dermal matrix.
The ideal approach to complex ventral hernia repair is frequently debated. Differences in processing techniques among biologic materials may impact hernia repair outcomes. This study evaluates the outcomes of hernia repair with a terminally sterilized human acellular dermal matrix (TS-HADM) (AlloMax(®) Surgical Graft, by C. R. Bard/Davol, Inc., Warwick, RI, USA) treated with low-dose gamma irradiation. A single-arm multi-center retrospective observational study of patients undergoing hernia repair with TS-HADM was performed. Data analyses were exploratory only; no formal hypothesis testing was pre-specified. Seventy-eight patients (43F, 35M) underwent incisional hernia repair with a TS-HADM. Mean follow-up was 20.5 months. Preoperative characteristics include age of 56.6 ± 11.1 years, BMI 36.7 ± 9.9 kg/m(2), and mean hernia defect size 187 cm(2). Sixty-five patients underwent component separation technique (CST) with a reinforcing graft. Overall, 21.8% developed recurrences. Recurrences occurred in 15% of patients repaired with CST. Major wound complications occurred in 31% of patients overall. Based upon CDC surgical wound classification, major wound complications were seen in 26, 40, 56, and 50% of Class 1, 2, 3, and 4 wounds, respectively. No grafts required removal. Hernia recurrences are not uncommon following complex abdominal wall reconstruction. Improved outcomes are seen when a TS-HADM is utilized as reinforcement to primary fascial closure.


Primary sequence and functional expression of a novel beta subunit of the P-ATPase gene family.
The cortical collecting tubule (CCT) of the mammalian kidney reabsorbs sodium and potassium, processes that are mediated by Na/K-ATPase and H/K-ATPase. CCT is also an important site for proton secretion, which is driven, in part, by H/K-ATPase. Na/K-ATPase and H/K-ATPase are members of the ion-motive P-ATPase gene family. They are closely related plasma membrane proteins which consist of alpha beta heterodimers. The urinary bladder of the toad Bufo marinus is the amphibian counterpart of mammalian CCT. We have previously characterized a ouabain-resistant Na/K-ATPase [see ref. 17], from TBM cells, a clonal cell line derived from the toad bladder, which expresses transepithelial sodium transport. In the present study, we report the primary sequence and functional expression of a novel beta subunit (beta bladder = beta b1) isolated from a toad bladder epithelial cell cDNA library. The deduced polypeptide is 299 amino acids in length and has a predicted molecular mass of 33 kDa. The beta b1 protein exhibits 35% amino acid identity to the previously characterized beta 1 of B. marinus Na/K-ATPase and 39% identity with beta 3 of B. marinus Na/K-ATPase. It shares 38% identity with the mammalian beta gastric H/K-ATPase and 52% with the mammalian beta 2 Na/K-ATPase. Northern blot analysis shows that a 1.4 x 10(3)-base mRNA is expressed at a high level in bladder epithelial cells and eye and at a trace level in kidney; it is not detectable in significant amounts in the stomach, colon and small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)


Altered blood pressure reactivity in adolescent diabetics.
We examined hemodynamic responses to a variety of physiologic stimuli in 14 normotensive adolescents with type I diabetes and 45 healthy controls to determine whether structural vascular changes contribute to a reduced vasodilator capacity in adolescent diabetics. We asked, in adolescents with type I diabetes: (1) Are structural vascular changes present? (2) Are changes in the systemic vascular bed reflected in abnormal blood pressure regulation? and (3) Is abnormal vascular reactivity associated with either diabetes duration or control? Diabetic subjects were outpatients treated at the Medical College of Virginia, ages 13 to 18 years. Diabetes duration averaged 7.5 years. Each subject underwent an echocardiogram, dynamic and isometric exercise testing, and forearm plethysmography. Compared to controls, diabetic subjects had (1) higher systolic and diastolic blood pressure during dynamic and handgrip exercise, (2) decreased forearm vasodilator capacity in response to ischemia, and (3) an increased aortic peak velocity. Group diastolic filling abnormalities were found, but these did not persist after adjustment for heart rate. The following variables were related to both diabetes duration and control (average glycosylated hemoglobin): (1) diastolic blood pressure during dynamic exercise, (2) resting forearm vascular resistance, and (3) forearm vascular reactivity. In addition, diabetes duration correlated with isometric exercise diastolic blood pressure, and diabetes control correlated with resting diastolic blood pressure. In young diabetics we found that (1) abnormalities of the resistance vessels of the forearm may be present, (2) the degree of vascular change is related to diabetes duration and control, and (3) aortic distensibility may be impaired.


Kinetics of antigen cross-presentation assessed experimentally and by a model of the complete endomembrane system.
Dendritic cells (DCs) have a specialized endomembrane system capable of presenting exogenous antigens in the context of MHC class I (MHC-I) molecules. This process, named cross-presentation, is crucial to activate CD8+ T lymphocytes and initiate cytotoxic immune responses. In this report, we present an Agent-Based Model in combination with Ordinary Differential Equations with enough complexity to reproduce cross-presentation. The model embraces the secretory and endocytic pathways, in connection with the plasma membrane, the endoplasmic reticulum, and the cytosol. Key molecules required for cross-presentation were included as cargoes. In the simulations, the kinetics of MHC-I uptake and recycling, and cross-presentation accurately reproduced experimental values. The model proved to be a suitable tool to elaborate hypotheses and design experiments. In particular, the model predictions and the experimental results obtained indicate that the rate-limiting step in cross-presentation of soluble ovalbumin is MHC-I loading after proteasomal processing of the antigenic protein.


Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations.
We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.


The prognostic variability of ovarian tumor grading by different pathologists.
In a multicenter ovarian tumor study, it was shown that there are considerable differences between different pathologists when grading the same ovarian tumors. The question arises whether these differences in grading also reflect prognostic differences. To investigate this, the survival curves of the various tumor grades assigned to the same tumors by four different pathologists were investigated. The results of the present study indicate that tumor grade was strongly correlated with the prognosis, although there were considerable variations in the survival curves and in the five year survival of patients of the same grade assessed by the different pathologists. Five-year survival varied from 82 to 100% in the borderline tumors, from 49 to 80% in the well, and from 21 to 48% in the moderately differentiated tumor groups. Only the poorly differentiated cancers showed less variation. Similar interobserver differences were found in the histological typing and (strictly predefined) malignancy grades. The intraobserver variation, which was also tested after a 6-month interval, was somewhat lower, but was still present for each of the pathologists. These data clearly indicate the necessity for objective, sharply defined, reproducible criteria rather than subjective grades.


The '3 Rs' and neuropsychological function in schizophrenia: a test of the matching fallacy in biological relatives.
The 'matching fallacy' suggests that matching schizophrenic patients and normal control subjects on education or IQ may cause systematic mismatching of theoretically expected ability. This study supports a modest version of the matching fallacy effect in nonpsychotic biological relatives of schizophrenic patients. At equivalent levels of education, relatives and control subjects had similar Reading and Spelling scores on the Wide Range Achievement Test-Revised--measures that are largely unimpaired by schizophrenia-related processes. However, relatives showed a deficit in IQ (primarily verbal IQ) compared with what would be predicted from their Reading scores. A similar deficit in Arithmetic scores was found in non-college-educated relatives, but college-educated relatives showed an advantage. We discuss possible implications of the findings with regard to genetic and environmental factors.


A model for detection of spatial and temporal edges by a single X cell.
When an inhibitory visual stimulus is turned off, an increased rate of spike discharge is evoked which we term the "rebound response". This response exists as a part of different cell responses from the retina to the cortex. The rebound response, with its temporal dependence on stimulus parameters, has not been previously considered in models. Here we present such a model, and also show its dependence on stimulus duration and its turning off rate. The rebound response enables detection of temporal changes when a visual stimulus involves spatial changes. The temporal change detection is affected by the actual stimulus duration, which can also be seen as a cell memory operation.


A Family of Octahedral Magnetic Molecules Based on [NbIV(CN)8]4.
A building block approach has been used to prepare a new family of hexanuclear magnetic molecules Mn4Nb2, Fe4Nb2, and Co4Nb2 of general formula {[MII(tmphen)2]4[NbIV(CN)8]2}·solv (M = Mn, Fe, Co; tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline; solv = MeOH and/or H2O). Mn4Nb2 exhibits a magnetocaloric effect at temperatures close to 1.8 K, and Fe4Nb2 undergoes an incomplete gradual spin crossover and a photomagnetic response related to light-induced excited spin state trapping.


[Heterozygous familial hypercholesterolemia in Spain. Description of 819 non related cases].
Heterozygous familial hypercholesterolemia (hFH) is an inherited disorder commonly found among the general population. Premature cardiovascular disease, especially coronary artery disease, is the most important complication in these patients. The aim of this study was to analyze the clinical manifestations and the characteristics of cardiovascular disease in the Spanish hFH population. Analysis of 819 non-related cases (449 females and 370 males), with a clinical diagnosis of familial hypercholesterolemia, from 69 lipid clinics. Clinical and lipid profile at diagnosis along with personal and familial backgrounds related to cardiovascular disease were registered in a central database. Mean total cholesterol at diagnosis was 412 (87) mg/dl in women, and 400 (78) mg/dl in men (p = 0.049). HDL-c was higher in females than in males (57 [14] vs. 47.7 [12.7] mg/dl, respectively, p < 0.0001). Xantomas were present in 22.5% of cases, and 21.7% of subjects had evidence of premature cardiovascular disease which was more frequent in males than in females (30.8% and 14.3%, respectively; p < 0.001). In a multivariant analysis, a significant and positive correlation was observed between cardiovascular disease and age, gender, tobacco consumption, LDL-c levels, blood pressure and body mass index. The clinical manifestations and the presence of cardiovascular disease in Spanish hFH patients are similar to those described in other populations. LDL-c levels, age, gender, smoking, hypertension and body mass index are important predictors of cardiovascular disease in these patients.


Discovery of covalent prolyl oligopeptidase boronic ester inhibitors.
Over the past decade, many drug discovery endeavors have been invested in targeting the serine proteases prolyl oligopeptidase (POP) for the treatment of Alzheimer's and Parkinson's disease and, more recently, epithelial cancers. Our research group has focused on the discovery of reversible covalent inhibitors, namely nitriles, to target the catalytic serine residue in this enzyme. While there have been many inhibitors discovered containing a nitrile to covalently bind to the catalytic serine, we have been investigating others, particularly boronic acids and boronic esters, the latter of which have been largely unexplored as covalent warheads. Herein we report a series of computationally-designed POP boronic ester pro-drug inhibitors exhibiting nanomolar-potencies in vitro as their active boronic acid species. These easily-accessible (1-2 step syntheses) compounds could facilitate future biochemical and biological studies of this enzyme's role in neurodegenerative diseases and cancer progression.


A study of the use of autoclave bags in non-vacuum autoclaves.
Two types of autoclave bags have been tested in five commonly used dental, non-vacuum autoclaves. The bags did not prevent the sterilization of instruments provided that most of the air was removed and the bags of instruments were not stacked. The use of a sterilization indicator in the bag is mandatory.


Experimental study of cervical blockage induced by continuous low-dose oral progestogens.
An investigation correlating scanning electron microscopic observations with sperm penetration tests carried out on cervical mucus under the influence of low-dose continuous progestogen (Norgestrienone) is presented. The results demonstrate that such type of contraceptive is involved in drastic alterations of mid-cycle cervical mucus at the macromolecular level. The meshwork which constitutes the infrastructure of the cervical secretion appears to be greatly tightened as a result of the treatment, thus giving the woof a general appearance typical of cervical mucus in the late luteal phase. The immobilizing effect of such modified mucus on spermatozoa is demonstrated and the duration of effectiveness after the administration of a last pill on the morning of day 13 is determined.


The Prevalence of Social Frailty Among Older Adults: A Systematic Review and Meta-Analysis.
To report the overall prevalence of social frailty among older people and provide information for policymakers and authorities to use in developing policies and social care. A systematic review and meta-analysis. We searched 4 databases (PubMed, Embase, Web of Science, and Google Scholar) to find articles from inception to July 30, 2022. We included cross-sectional and cohort studies that provided the prevalence of social frailty among adults aged 60 years or older, in any setting. Three researchers independently reviewed the literature and retrieved the data. A risk of bias tool was used to assess each study's quality. A random-effect meta-analysis was performed to pool the data, followed by subgroup analysis, sensitivity analysis, and meta-regression. From 761 records, we extracted 43 studies with 83,907 participants for meta-analysis. The pooled prevalence of social frailty in hospital settings was 47.3% (95% CI: 32.2%-62.4%); among studies in community settings, the pooled prevalence was 18.8% (95% CI: 14.9%-22.7%; P < .001). The prevalence of social frailty was higher when assessed using the Tilburg Frailty Indicator (32.3%; 95% CI: 23.1%-41.5%) than the Makizako Social Frailty Index (27.7%; 95% CI: 21.6%-33.8%) or Social Frailty Screening Index (13.4%; 95% CI: 8.4%-18.4%). Based on limited community studies in individual countries using various instruments, social frailty was lowest in China (4.9%; 95% CI: 4.2%-5.7%), followed by Spain (11.6%; 95% CI: 9.9%-13.3%), Japan (16.2%; 95% CI: 12.2%-20.3%), Korea (26.6%; 95% CI: 7.1%-46.1%), European urban centers (29.2%; 95% CI: 27.9%-30.5%), and the Netherlands (27.2%; 95% CI: 16.9%-37.5%). No other subgroup analyses showed any statistically significant prevalence difference between groups. The prevalence of social frailty among older adults is high. Settings, country, and method for assessing social frailty affected the prevalence. More valid comparisons will await consensus on measurement tools and more research on geographically representative populations. Nevertheless, these results suggest that public health professionals and policymakers should seriously consider social frailty in research and program planning involving older adults.


Serious or fatal driver injury rate versus car mass in head-on crashes between cars of similar mass.
This work was performed to determine relations between car mass and driver injuries (serious or fatal) when cars of similar mass crash into each other head-on. This type of crash is examined because it is considered similar in some respects to a barrier crash. Data from the United States Fatal Accident Reporting System (FARS) are used to examine driver fatality likelihood as a function of car mass when cars of similar mass crash into each other. Pedestrian fatalities involving cars of the same mass are used to estimate exposure. Two additional sources of data (State data from North Carolina and New York) are used to generate information on the number of drivers seriously injured or killed per police reported crash when cars of similar mass crash into each other. The present study finds that the likelihood of driver injury (fatal or serious) when cars of similar mass crash into each other increases with decreasing car mass, both for head-on crashes and for crashes in all directions. The study does not address possible mechanisms that might lead to such relations. All the data analyzed reveal a fairly consistent picture--a driver in a 900 kg car crashing head-on into another 900 kg car is about 2.0 times as likely to be seriously injured or killed as is a driver of a 1800 kg car crashing head-on into another 1800 kg car.


Fluoxetine prevents LPS-induced degeneration of nigral dopaminergic neurons by inhibiting microglia-mediated oxidative stress.
Lipopolysaccharide (LPS)-induced microglial activation causes degeneration of nigral dopaminergic (DA) neurons. Here, we examined whether fluoxetine prevents LPS-induced degeneration of DA in the rat substantia nigra (SN) in vivo. Seven days after LPS injection into the SN, immunostaining for tyrosine hydroxylase (TH) revealed a significant loss of nigral DA neurons. Parallel activation of microglia (visualized by OX-42 and ED1 immunohistochemistry), production of reactive oxygen species (ROS) (assessed by hydroethidine histochemistry), and degeneration of nigral DA neurons were also observed in the SN. Western blot analyses and double-label immunohistochemistry showed an increase in the expression of inducible nitric oxide synthase (iNOS) within activated microglia. LPS also induced translocation of p67(phox), the cytosolic component of NADPH oxidase, to the membrane of SN microglia, indicating activation of NADPH oxidase. The LPS-induced loss of nigral DA neurons was partially inhibited by fluoxetine, and the observed neuroprotective effects were associated with fluoxetine-mediated suppression of microglial NADPH oxidase activation and iNOS upregulation, and decreased ROS generation and oxidative stress. These results suggest that fluoxetine and analogs thereof may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with microglia-derived oxidative damage.


Perceived Occupational Stressors and the General Health of Critical Care Nurses During COVID-19 Pandemic.
The COVID-19 situation is placing nurses under great stress which may negatively influence their health. The purpose of this study was to examine the association between occupational stress and general health of critical care nurses during COVID-19 pandemic. A descriptive, cross-sectional design was used. A convenience sample of 150 Jordanian critical care nurses completed the study. Occupational stress was a significant predictor of nurses' general health. Female gender, young, living with elderly or persons having chronic diseases, and little nursing experience were associated with worse general health, while living with elderly or persons having chronic diseases were associated with more occupational stress. Providing psychological support services for critical care nurses is required to reduce the impact of occupational stress on nurses' poor general health.


Evaluation of multidisciplinary pulmonary rehabilitation education delivered by either DVD or spoken talk.
Pulmonary rehabilitation (PR) is a multidisciplinary program of care for patients with chronic respiratory disease. The educational component is an integral component and represents a large proportion of a program. However, it can be difficult to secure regular multidisciplinary input to PR programs. This service evaluation assessed whether DVD presentations are acceptable to patients and effective as an education medium. Two PR groups were compared; one group received education by DVD and the other by spoken talk. Both groups evaluated the content and delivery of each session and their knowledge was measured using the Bristol COPD Knowledge Questionnaire (BCKQ). One hundred and twenty-three patients with Chronic Obstructive Pulmonary Disease (COPD) took part; 58 evaluated the DVD, 75 the talk sessions. There were no differences between the two groups at baseline with respect to age, gender distribution, or FEV1 . Both groups were satisfied with the content (99.46% DVD, 100% talk group) and delivery (100% both DVD and talk groups) of their education sessions. At baseline, there were no between group differences in the mean BCKQ. After PR, significant changes in BCKQ scores were seen within the groups (6.52 points (1.48-11.37) DVD group and 8.96 points (6.50-11.19) talk group), again with no differences between the groups. A DVD-based education package is both acceptable to PR patients and effective at improving patients' knowledge of COPD. Using filmed educational talks with PR would have a number of benefits to both the patients and the service and may be a way of increasing the capacity of PR services.


Assignment of the low-temperature fluorescence in oxygen-evolving photosystem II.
Low-temperature absorption and fluorescence spectra of fully active cores and membrane-bound PS II preparations are compared. Detailed temperature dependence of fluorescence spectra between 5 and 70 K are presented as well as 1.7-K fluorescence line-narrowed (FLN) spectra of cores, confirming that PS II emission is composite. Spectra are compared to those reported for LHCII, CP43, CP47 and D1/D2/cytit b559 subunits of PS II. A combination of subunit spectra cannot account for emission of active PS II. The complex temperature dependence of PS II fluorescence is interpretable by noting that excitation transfer from CP43 and CP47 to the reaction centre is slow, and strongly dependent on the precise energy at which a 'slow-transfer' pigment in CP43 or CP47 is located within its inhomogeneous distribution. PS II fluorescence arises from CP43 and CP47 'slow-transfer' states, convolved by this dependence. At higher temperatures, thermally activated excitation transfer to the PS II charge-separating system bypasses such bottlenecks. As the charge-separating state of active PS II absorbs at >700 nm, PS II emission in the 680-700 nm region is unlikely to arise from reaction centre pigments. PS II emission at physiological temperatures is discussed in terms of these results.


Evaluation of First Seizure and Newly Diagnosed Epilepsy.
This article focuses on the evaluation of children and adults who present with new-onset seizures, with an emphasis on differential diagnosis, classification, evaluation, and management. New-onset seizures are a common presentation in neurologic practice, affecting approximately 8% to 10% of the population. Accurate diagnosis relies on a careful history to exclude nonepileptic paroxysmal events. A new classification system was accepted in 2017 by the International League Against Epilepsy, which evaluates seizure type(s), epilepsy type, epilepsy syndrome, etiology, and comorbidities. Accurate classification informs the choice of investigations, treatment, and prognosis. Guidelines for neuroimaging and laboratory and genetic testing are summarized. Accurate diagnosis and classification of first seizures and new-onset epilepsy are key to choosing optimal therapy to maximize seizure control and minimize comorbidities.


Engineering of cysteine residues leads to improved production of a human dipeptidase enzyme in E. coli.
Low yields, poor folding efficiencies and improper disulfide bridge formation limit large-scale production of cysteine-rich proteins in Escherichia coli. Human renal dipeptidase (MDP), the only human beta-lactamase known to date, is a homodimeric enzyme, which contains six cysteine residues per monomer. It hydrolyses penem and carbapenem beta-lactam antibiotics and can cleave dipeptides containing amino acids in both D: - and L: -configurations. In this study, MDP accumulated in inactive form in high molecular weight, disulfide-linked aggregates when produced in the E. coli periplasm. Mutagenesis of Cys361 that mediates dimer formation and Cys93 that is unpaired in the native MDP led to production of soluble recombinant enzyme, with no change in activity compared with the wild-type enzyme. The removal of unpaired or structurally inessential cysteine residues in this manner may allow functional production of many multiply disulfide-linked recombinant proteins in E. coli.


Effects of 2 quinolone antibacterials, temafloxacin and enoxacin, on theophylline pharmacokinetics.
Certain quinolone and naphthyridone antibacterial agents reduce the clearance of theophylline, posing potential clinical risks for patients maintained on this bronchodilator. Whether temafloxacin also affects theophylline pharmacokinetics was assessed in a randomised double-blind 3-way crossover study in 12 healthy volunteers, using placebo and enoxacin as controls. Each volunteer participated in all 3 phases of the study, receiving theophylline plus daily divided doses of temafloxacin 800mg, enoxacin 800mg, or placebo, orally for 7 days. Aminophylline 200mg (containing 146mg theophylline) was given orally twice daily on the first 4 days. On the fifth morning, theophylline 200mg was administered intravenously, and serial blood and urine samples were collected for the following 72h. Coadministration of enoxacin significantly reduced the metabolic clearance of theophylline (approximately 65%). In contrast, during coadministration of temafloxacin, theophylline pharmacokinetics did not differ significantly from those during coadministration of placebo. No clinically significant adverse events occurred; total reported adverse events during enoxacin-theophylline administration (n = 33) were higher than those reported during temafloxacin-theophylline administration (n = 22) and theophylline alone (n = 23). Administration of temafloxacin to patients on long term theophylline therapy appears to be a safe and rational choice when treatment with a broad spectrum antibiotic is indicated.


A novel I551F variant of the Na+/HCO3- cotransporter NBCe1-A shows reduced cell surface expression, resulting in diminished transport activity.
Homozygous mutations in SLC4A4, which encodes the electrogenic Na+/[Formula: see text] cotransporter (NBCe1), cause proximal renal tubular acidosis associated with extrarenal symptoms. Although 17` mutated sites in SLC4A4 have thus far been identified among patients with proximal renal tubular acidosis, the physiological significance of other nonsynonymous single-nucleotide variants (SNVs) remains largely undetermined. Here, we investigated the functional properties of SNVs in NBCe1. From the National Center for Biotechnology Information dbSNP database, we identified 13 SNVs that have not previously been characterized in the highly conserved, transmembrane domains of NBCe1-A. Immunocytochemical analysis revealed that the I551F variant was present predominantly in the cytoplasm in human embryonic kidney (HEK)-293 cells, whereas all other SNVs did not show as dramatic a change in subcellular distribution. Western blot analysis in HEK-293 cells demonstrated that the I551F variant showed impaired glycosylation and a 69% reduction in cell surface levels. To determine the role of I551 in more detail, we examined the significance of various artificial mutants in both nonpolarized HEK-293 cells and polarized Madin-Darby canine kidney cells, which indicated that only I551F substitution resulted in cytoplasmic retention. Moreover, functional analysis using Xenopus oocytes demonstrated that the I551F variant had a significantly reduced activity corresponding to 39% of that of the wild-type, whereas any other SNVs and artificial I551 mutants did not show significant changes in activity. Finally, immunofluorescence experiments in HEK-293 cells indicated that the I551F variant retained wild-type NBCe1-A in the cytoplasm. These data demonstrate that the I551F variant of NBCe1-A shows impaired transport activity predominantly through cytoplasmic retention and suggest that the variant can have a dominant negative effect by forming complexes with wild-type NBCe1-A.NEW & NOTEWORTHY Electrogenic Na+/[Formula: see text] cotransporter 1-A (NBCe1-A) in the proximal tubule regulates the acid/base balance and fluid volume homeostasis. From the National Center for Biotechnology Information dbSNP database, we identified the I551F variant of NBCe1-A, which showed reduced glycosylation, cell surface expression, and transport activity. We also found that the I551F variant can exert a dominant negative effect on wild-type NBCe1-A, suggesting its physiological significance.


Knee joint meniscal degeneration as it relates to tissue fiber structure and mechanical resistance.
Histological examination of knee joint meniscectomy specimens revealed previously undescribed basophilic spindle shaped structures. This study was done to explore their structure, to discuss potential mechanisms for their development and to establish diagnostic criteria. --4000 surgical specimens were examined. The intercellular substance of the cartilage was studied by means of mucopolysaccharide histochemical and polarisation optical methods. The three-dimensional fiber construction was examined stereometrically by means of a procedure derived from the universal stage method of the mineralogists. The spindle-shaped structures seem to be a sign of reduced mechanical tissue resistance. They are performed but become visible during meniscal degeneration. The mechanically efficient element of the menisci is a triple dimensional network of collagen fibers. Longitudinal fibers assure the tension resistance of the tissue. Transverse and diagonal fiber bundles tie the longitudinal fibers together. They act as tension rods. Therefore, compression resistance results. Meniscal degeneration mainly takes place in the tension rod fibers. Therefore, degenerated menisci tend to burst longitudinally. The condition of tension rod fibers in important as an indicator of mechanical resistance of the cartilage. It is a parameter for the assessment of meniscal damage.


Estimation of milkability breeding values and variance components for Italian Holstein.
The importance of milkability as a trait is growing because of the need to efficiently use labor and machinery; therefore, it is crucial to update the statistical model for the trait to improve the accuracy of the estimated breeding values, and thus provide a more accurate tool for decision-making at the farm level. In the Italian Holstein Friesian cattle population, milkability is recorded twice a year by the milk recording system as a binary trait (slow, coded as 2, or not slow, coded as 1). Data consisted of 7,862,371 records from 2,945,249 cows collected between 2004 and 2021. A single-trait threshold animal model with repeated measures was used, with parity, days in milk class, calving season, and regression of production (fat + protein grams) within days in milk class as fixed effects and herd-year-season of recording, permanent environment, and animal as random effects. The results for heritability and repeatability were 0.275 and 0.5, estimated with the Gibbs sampler THRGIBBS1F90. Genomic validation, carried out using genotyped proven bulls born before 2009 as the training set, gave a result of 0.386 for reliability. The genetic correlations of this trait confirmed that both extremes of the estimated breeding value must be treated cautiously, because correlations with important traits such as mastitis resistance, body condition score, and teat length are unfavorable.


Metabolic oxygen regulation and conformity during submergence in the salamandersSiren lacertina, Amphiuma means, andAmphiuma tridactylum, and a comparison with other giant salamanders.
The giant salamanders of North America include 4 genera, all of which are aquatic. We have compared the efficacy of aquatic O2 uptake among them by measuring theVO2 while submerged and determining the responses to progressive hypoxia at 10-240 mmHg at 20° C. Both species ofAmphiuma were metabolic O2 conformers over the entire range ofPO2. About half ofSiren lacertina were conformers over this range, and half were regulators with an average critical O2 tension of 92 mmHg. There were no short-term changes (days) in the response ofSiren to progressive hypoxia, but one animal switched from conformation to regulation after 4-5 months. Neither genus is considered to have an exceptionally low metabolic rate. The "whole-body O2 conductance", defined asΔVO2/ΔPO2(µl O2 · g-1 · h-1 · mmHg-1) in the range of metabolic O2 conformity, was least in the species most dependent upon air-breathing and most likely to be found in hypoxic waters (e.g., 0.076 forAmphiuma), and greatest in those that airbreathe less frequently and/or are found in relatively normoxic waters (e.g., 0.429 forNecturus). These conductances are considered to be adaptive in terms of preventing O2 loss through the skin, or in facilitating its uptake, as correlated with the O2 tensions normally prevailing in the environment of each species.


Cervicovestibular rehabilitation in adult with mild traumatic brain injury: a randomised controlled trial protocol.
Mild traumatic brain injury (mTBI) is an acknowledged public health problem. Up to 25% of adult with mTBI present persistent symptoms. Headache, dizziness, nausea and neck pain are the most commonly reported symptoms and are frequently associated with cervical spine and vestibular impairments. The most recent international consensus statement (2017 Berlin consensus) recommends the addition of an individualized rehabilitation approach for mTBI with persistent symptoms. The addition of an individualized rehabilitation approach including the evaluation and treatment of cervical and vestibular impairments leading to symptoms such as neck pain, headache and dizziness is, however, recommended based only on limited scientific evidence. The benefit of such intervention should therefore be further investigated. To compare the addition of a 6-week individualized cervicovestibular rehabilitation program to a conventional approach of gradual sub-threshold physical activation (SPA) alone in adults with persistent headache, neck pain and/or dizziness-related following a mTBI on the severity of symptoms and on other indicators of clinical recovery. We hypothesize that such a program will improve all outcomes faster than a conventional approach (between-group differences at 6-week and 12-week). In this single-blind, parallel-group randomized controlled trial, 46 adults with subacute (3 to12 weeks post-injury) persistent mTBI symptoms will be randomly assigned to: 1) a 6-week SPA program or 2) SPA combined with a cervicovestibular rehabilitation program. The cervicovestibular rehabilitation program will include education, cervical spine manual therapy and exercises, vestibular rehabilitation and home exercises. All participants will take part in 4 evaluation sessions (baseline, week 6, 12 and 26) performed by a blinded evaluator. The primary outcome will be the Post-Concussion Symptoms Scale. The secondary outcomes will be time to clearance to return to function, number of recurrent episodes, Global Rating of Change, Numerical Pain Rating Scale, Neck Disability Index, Headache Disability Inventory and Dizziness Handicap Inventory. A 2-way ANOVA and an intention-to-treat analysis will be used. Controlled trials are needed to determine the best rehabilitation approach for mTBI with persistent symptoms such as neck pain, headache and dizziness. This RCT will be crucial to guide future clinical management recommendations. ClinicalTrials.gov Identifier - NCT03677661, Registered on September, 15th 2018.


The association between total bilirubin and serum triglyceride in both sexes in Chinese.
Dyslipidemia can cause some chronic diseases. Bilirubin is reported to have anti-inflammatory and anti-oxidant properties. We aimed to explore the relationship between triglyceride and total bilirubin (TB) in a large Chinese cohort. A total of 80,298 healthy Chinese (48,971 male, 31,327 female) enrolled in this cross-sectional study. Clinical data were collected from participants. Database was divided according to sex and age. The relationship between triglyceride and TB was analyzed by quartiles of TB. Levels of triglyceride were compared in different TB subgroups by one-way analysis of variance and independent sample's t-test. Crude and adjusted odds ratios of triglyceride for TB with 95% confidence intervals were analyzed by binary logistic regression models. Overall, men showed higher levels of TB and triglyceride than women. In people older than 60 years, women had higher triglyceride levels than men. Linear logistic regression analyses showed a negative relationship between triglyceride and TB in both genders. Men showed significantly higher overall incidence of high triglyceride than women. Men less than 60 years old showed a higher incidence of high triglyceride. For women older than 60 years, the incidence of high triglyceride was higher. However, high TB showed no protective effects on both genders from high TG in the binary logistic regression models. TB showed a detrimental effect on high TG in model 2 which included TB as a covariate. But that effect disappeared after other confounding factors were included. Our findings showed no association between TB and triglyceride in Chinese.


Changes in Medicare reimbursement for echocardiographic procedures.
Medicare reimbursement for echocardiographic procedures is clouded by the fact that Medicare defines ultrasound services to be "radiologic." As such, a 40% limitation has been imposed in some states. In addition, as a result of the Omnibus Budget Reconciliation Act of 1987, a new radiology fee structure was negotiated with Medicare, without the input of internists and cardiologists, that may significantly affect reimbursement patterns for echocardiographic services. Those who perform and interpret cardiac ultrasound studies are again urged to use the medicine codes (90,000 series) rather than radiology codes (70,000 series).


Duchenne's dystrophy associated with unusual musculoskeletal abnormalities. A case report.
A case of Duchenne's pseudohypertrophic muscular dystrophy allied with previously unreported musculoskeletal abnormalities is reported. Some of the more characteristic features of Duchenne's dystrophy are reviewed from the literature.


Long sleep duration is associated with cognitive frailty among older community-dwelling adults: results from West China Health and Aging Trend study.
To investigate the association between sleep duration and cognitive frailty among older adults dwelling in western China. We used the baseline data from West China Health and Aging Trend (WCHAT) study. Sleep duration was classified as short sleep duration (< 6 h), normal sleep duration (6-8 h) and long sleep duration (≥ 9 h). Fried frailty criteria and Short Portable Mental Status Questionnaire were used to measure cognitive frailty. Multinomial logistic regression was conducted to estimate odds ratio (OR) and 95% confidence interval (CI). A total of 4093 older adults (age = 67.8 ± 5.9 years, 1708 males and 2385 females) were included in the analysis. The prevalence of cognitive frailty was 11.8% among older adults in western China. Approximately 11.9% participants had short sleep duration (< 6 h); 22.2% had a long sleep duration (≥ 9 h). After adjusting for covariates, only long sleep duration was significantly associated with high risk of cognitive frailty (OR = 2.07, 95%CI = 1.60-2.68, P < 0.001) in western China older adults compared to normal sleep duration. Long sleep duration was significantly related to cognitive frailty in older adults. Intervention for long sleep duration may be helpful to prevent cognitive frailty. Chinese Clinical Trial Registry: ChiCTR1800018895 .


Determinants of Long-Term Survival in Metastatic Choroidal and Ciliary Body Melanoma.
To build and validate a prognostic model that predicts long-term overall survival (OS) in metastatic choroidal and ciliary body melanoma (CCBM) to facilitate patient counseling and planning, reporting, and interpreting clinical trials. Retrospective cohort study with validation. We analyzed predictors of intermediate (IMT; 25-<42 months) and long-term (LT; ≥42 months) OS in a Finnish nationwide cohort of 330 patients with metastatic CCBM. Short-term (<25 months), IMT, and LT survival were compared with pairwise and ordinal logistic regression. A single-center cohort of 259 patients from Italy was used for validation. Models were compared with a deviance test. Median OS was 12 and 17 months in the building and validation datasets, respectively; 40 (12%) and 31 (9%) compared with 44 (17%) and 32 (12%) patients were IMT and LT survivors, respectively. Alkaline phosphatase or lactate dehydrogenase level never exceeded 2 times the upper normal limit (UNL) in either LT cohort. Conditional to both being ≤2 times the UNL, distant metastasis-free interval (DMFI) >42 months (odds ratio [OR] 4.09-4.64; P < .001) paired with age <60 years (OR 3.23; P = .002), having no symptoms (OR 4.19; P = .005), and the largest diameter of the largest metastasis <30 mm (Tumor, Node, Metastasis stage M1a; OR 3.05; P = .001) independently predicted higher odds of surviving longer (IMT or LT) without model preference. These results were confirmed in the validation dataset. Alkaline phosphatase or lactate dehydrogenase >2 times the UNL essentially precluded LT survival. The most robust predictor otherwise was DMFI >42 months, followed by age <60 years, absence of symptoms, and Tumor, Node, Metastasis stage M1a.


The spatial distribution of physicochemical parameters in coastal sediments along the Bay of Bengal Coastal Zone with statistical analysis.
The current study focused on the monitoring of pollution loads in the Kalpakkam coastal zone of India in terms of physico-chemical characteristics of sediment. The investigation took place at 12 sampling points around the Kalpakkam coastal zone for one year beginning from 2019. The seasonal change of nutrients in the sediment, such as nitrogen, phosphorus, potassium, total organic carbon, and particles size distribution, was calculated. Throughout the study period, the pH (7.55 to 8.99), EC (0.99 to 4.98 dS/m), nitrogen (21.74 to 58.12 kg/ha), phosphorus (7.5 to 12.9 kg/ha), potassium (218 to 399 kg/ha), total organic carbon (0.11 to 0.88%), and particle size cumulative percent of sediments (from 9.01 to 9.39%) was observed. A number of multivariate statistical techniques were used to examine the changes in sediment quality. The population means were substantially different according to the three-way ANOVA test at the 0.05 level. Principal component analysis and cluster analysis showed a substantial association with all indicators throughout all seasons, implying contamination from both natural and anthropogenic causes. The ecosystem of the Kalpakkam coastal zone has been affected by nutrient contamination.


Antenatal mobile-delivered mindfulness-based intervention to reduce perinatal depression risk and improve obstetric and neonatal outcomes: A randomized controlled trial.
One in five mothers will experience perinatal depression (PND) during pregnancy and within their first year following childbirth. Current evidence suggests the short-term efficacy of Mindfulness-based interventions (MBI) for perinatal women, but the extent to which this positive impact remains the early postpartum period is unclear. This study investigated the short- and maintenance efficacy of a mobile-delivered four-immeasurable MBI on PND, and obstetric and neonatal outcomes. Seventy-five adult pregnant women suffering from heightened distress were randomized to receive a mobile-delivered four-immeasurable MBI (n = 38) or a web-based perinatal education program (n = 37). PND was measured by Edinburgh Postnatal Depression Scale at baseline, post-intervention, 37th-week gestation, and 4-6 weeks postpartum. Outcomes also included obstetric and neonatal outcomes, trait mindfulness, self-compassion, and positive affect. Participants reported an average age of 30.6 (SD = 3.1) years with a mean gestational age of 18.8 (SD = 4.6) weeks. In intention-to-treat analyses, women in the mindfulness group showed a significantly greater reduction in depression from baseline to post-intervention (adjusted mean change difference [β] = -3.9; 95%CI = [-6.05, -1.81]; d = -0.6), and the reduction sustained until 4-6 weeks postpartum (β = -6.3; 95%CI = [-8.43, -4.12]; d = -1.0), compared with control. They had a significantly reduced risk of emergent cesarean section (relative risk = 0.5) and gave birth to infants with higher Apgar scores (β = 0.6;p = .03; d = 0.7). Depression reduction before giving birth significantly mediated the intervention effect on lowering the emergency cesarean risk. With a reasonably low dropout rate (13.2 %), the mobile-delivered MBI can be an acceptable and effective intervention for reducing depression throughout pregnancy and postpartum. Our study also suggests the potential benefits of early prevention for mitigating emergent cesarean section risk and enhancing neonatal health.


Use of a D-optimal design with constrains to quantify the effects of the mixture of sodium, potassium, calcium and magnesium chloride salts on the growth parameters of Saccharomyces cerevisiae.
The combined effect of NaCl, KCl, CaCl(2), and MgCl(2) on the water activity (a (w)) and the growth parameters of Saccharomyces cerevisiae was studied by means of a D-optimal mixture design with constrains (total salt concentrations < or = 9.0%, w/v). The a (w) was linearly related to the concentrations of the diverse salts; its decrease, by similar concentrations of salts, followed the order NaCl > CaCl(2) > KCl > MgCl(2), regardless of the reference concentrations used (total absence of salts or 5% NaCl). The equations that expressed the maximum specific growth (mu (max)), lag phase duration (lambda), and maximum population reached (N (max)) showed that the values of these parameters depended on linear effects and two-way interactions of the studied chloride salts. The mu (max) decreased as NaCl and CaCl(2) increased (regardless of the presence or not of previous NaCl); however, in the presence of a 5% NaCl, a further addition of KCl and MgCl(2) markedly increased mu (max). The lambda was mainly affected by MgCl(2) and the interactions NaCl x CaCl(2) and CaCl(2) x MgCl(2). The further addition of NaCl and CaCl(2) to a 5% NaCl medium increased the lag phase while KCl and MgCl(2) had negligible or slightly negative effect, respectively. N (max) was mainly affected by MgCl(2) and its interactions with NaCl, KCl, and CaCl(2); MgCl(2) stimulated N (max) in the presence of 5% NaCl while KCl, NaCl, and CaCl(2) had a progressive decreasing effect. These results can be of interest for the fermentation and preservation of vegetable products, and foods in general, in which this yeast could be present.


Cytokine release in febrile non-haemolytic red cell transfusion reactions.
The aim of this study was to elucidate the role and identity of cytokines involved in febrile non-haemolytic red cell transfusion reactions (FNHTRs). Eighty-one patients experiencing transfusion reactions after receiving packed red blood cells (RBCs) were divided into three groups, as follows, based on the reaction experienced: FNHTRs (n = 60); chills without fever (n = 8); and allergic reaction with urticaria (n = 13). The concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumour necrosis factor (TNF)-alpha were measured in the packed transfused unit and patients' plasma by using enzyme immunoassays. Wilcoxon's matched-pairs signed test was used to compare the difference in cytokine levels in patients' plasma before and after transfusion. The Kruskal-Wallis test was used first, followed by the Mann-Whitney test, to compare the pretransfusion cytokine levels in patients' plasma between groups and to compare the cytokine levels in packed RBCs transfused to each group of patients. The age of the implicated packed RBC was 11.5 +/- 5.7 days. Significant increases were observed in IL-6 (P < 0.001) and IL-8 (P < 0.001) patients' plasma levels, but not in IL-1beta or TNF-alpha levels, in those patients exhibiting FNHTR. No changes were observed in the patients' plasma samples of the other groups. Cytokine levels in the RBC concentrate supernatants were not appreciably elevated. Transfusion of packed RBCs may significantly increase intravascular levels of IL-6 and IL-8 in patients with FNHTRs.


Diets, Gut Microbiota and Metabolites.
The gut microbiota refers to the gross collection of microorganisms, estimated trillions of them, which reside within the gut and play crucial roles in the absorption and digestion of dietary nutrients. In the past decades, the new generation 'omics' (metagenomics, transcriptomics, proteomics, and metabolomics) technologies made it possible to precisely identify microbiota and metabolites and describe their variability between individuals, populations and even different time points within the same subjects. With massive efforts made, it is now generally accepted that the gut microbiota is a dynamically changing population, whose composition is influenced by the hosts' health conditions and lifestyles. Diet is one of the major contributors to shaping the gut microbiota. The components in the diets vary in different countries, religions, and populations. Some special diets have been adopted by people for hundreds of years aiming for better health, while the underlying mechanisms remain largely unknown. Recent studies based on volunteers or diet-treated animals demonstrated that diets can greatly and rapidly change the gut microbiota. The unique pattern of the nutrients from the diets and their metabolites produced by the gut microbiota has been linked with the occurrence of diseases, including obesity, diabetes, nonalcoholic fatty liver disease, cardiovascular disease, neural diseases, and more. This review will summarize the recent progress and current understanding of the effects of different dietary patterns on the composition of gut microbiota, bacterial metabolites, and their effects on the host's metabolism.


History of successful ballot initiatives--Oregon.
In this report, the author traces the background of Ballot Measure 44, which raised taxes on cigarette and other tobacco products in Oregon. He highlights the effect of a positive coalescing of different forces (nonprofit health groups and medical groups) despite initial differences in program strategy.


Involvement of H2-receptors in the mechanism of analgesic action of Tyr-MIF-1.
The antinociceptive effects of H2-agents cimetidine (CIM) and dimaprit (DMP) as well as their effects on the Tyr-MIF-1-evoked analgesia have been studied after intraperitoneal (i.p.) administration in rats. In the paw-pressure (PP) test Tyr-MIF-1 (1 mg/kg), CIM (50 and 100mg/kg) and DMP (5 and 10mg/kg) induced analgesia. Injected before DMP, naloxone (NAL) and CIM diminished or completely prevented the pain-relieving effect of H2-agonist DMP. The antinociceptive effect of Tyr-MIF-1 has been potentiated by DMP dose-dependently. CIM (50mg/kg) decreased the antinociceptive action of the combination Tyr-MIF-1 + DMP, while CIM (100mg/kg) expressed a weaker inhibitory effect on it. The data obtained clearly show that H2-receptor activation is involved in the mechanism of the Tyr-MIF-1 antinociceptive action.


Crystallization and preliminary X-ray studies of the VL domain of the antibody McPC603 produced in Escherichia coli.
The VL domain, obtained from a recombinant Fv fragment of the antibody McPC603 expressed in Escherichia coli, has been crystallized as a dimer from 2 M-(NH4)2SO4 (pH 4.0). The crystals are hexagonal, space group P6(1)22. The cell dimensions are a = b = 86.48 A, c = 76.64 A, with a VL monomer as the asymmetric unit. The crystals diffract to 2.0 A. The structure was solved by Patterson search using the VL domain of the Fab fragment of McPC603 and the VL dimer REI.


From Intention to Action: Hierarchical Sensorimotor Transformation in the Posterior Parietal Cortex(12).
Cover FigureAlthough both the PRR and area 5d have been found to be intimately involved in visually guided reach, several recent studies of reference frame, decision making, and sequential movement suggest that they might play distinct roles in planning and control of reach at different levels of complexity, indicating a hierarchical circuitry participating in translation from abstract intention into concrete action plan.


Gallstones and isoflurane hepatitis.
This report is of a case of a previously fit 65-year-old woman who developed postoperative liver dysfunction following an anaesthetic involving isoflurane. Biliary ultrasound demonstrated gallstones. However, serum antibodies to trifluoroacetylated proteins were detected, suggesting that immune sensitisation to the anaesthetic could have contributed to the impaired liver function.


Neuroinflammation-induced parvalbumin interneuron and oscillation deficits might contribute to neurobehavioral abnormities in a two-hit model of depression.
Depression is a common neuropsychiatric disorder that causes profound disability worldwide, yet the underlying mechanism remains unclear. Thus, the present study aimed to evaluate the effects of a two-hit model of depression on glial activation, parvalbumin (PV) interneuron, oscillation activity, and behavior alternations, and whether chronic fluoxetine treatment can reverse these abnormalities. Male mice were submitted to lipopolysaccharide (LPS) injection, followed by a modified chronic unpredictable stress (CUS) protocol. In our study, we showed that mice exposed to LPS and CUS exhibited reduced body weight, anhedonic-like behavior as well as cognitive and anxiety symptoms. These behavioral alternations were related to enhanced neuroinflammation, as reflected by significantly increased IL-1β and IL-6 levels and microglia activation in the prefrontal cortex (PFC). In addition, mice exposed to LPS and CUS displayed significantly decreased PV expression and disturbance of theta and gamma oscillations in the PFC. However, chronic fluoxetine treatment reversed most of these abnormalities. In conclusion, our study suggests that neuroinflammation-induced PV interneuron and oscillation deficits might contribute to neurobehavioral abnormalities in a two-hit model of depression.


Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men.
Associations between intra-abdominal visceral fat accumulations and coronary risk factors were studied in a sample of 29 non-obese men aged 57 +/- 10 years with coronary artery disease (CAD). Their body mass indexes (BMI) were 23.8 +/- 1.5 (range 18.7-26.3). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured at the level of the umbilicus by computed tomography. In patients with CAD, the average VFA was significantly increased compared with that in 54 control subjects without CAD, matched for sex, age, and BMI (117.2 +/- 53.1 vs. 93.8 +/- 38.6 cm2, P < 0.05). However, their average SFA was not statistically different (111.2 +/- 33.3 vs. 106.3 +/- 35.7 cm2, N.S.). Eleven CAD patients (38%) and nine control subjects (17%) had greater than 2 S.D. higher than the mean VFA obtained from 22 healthy subjects extracted from the control subjects. Accordingly, the proportion of the subjects with high VFA was significantly higher in the CAD group. This group also had significantly higher levels of plasma glucose and insulin areas than controls determined by oral glucose tolerance tests. This may be due to insulin resistance. The proportion of the subjects with multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was significantly higher in the CAD patients with high VFA compared with the control subjects with normal VFA (CAD with high VFA 82% and control with normal VFA 33%). These findings suggest that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)


Frequency-specific age-related changes in the amplitude of spontaneous fluctuations in autism.
Autism spectrum disorder is characterized by atypical developmental changes during brain maturation, but regional brain functional changes that occur with age and across different frequency bands are unknown. Therefore, the current study aimed to explore potential age and frequency band-related changes in the regional brain activities in autism. A total of 65 participants who met the DSM-IV criteria for autistic disorder and 55 typically developed (TD) participants (both age 6-30 years) were recruited in the current study. The two groups were matched in age (t=-1.314, P=0.191) and gender (χ2=2.760, P=0.097). The amplitude of low-frequency fluctuations (ALFF) was employed to explore the effect of development on spontaneous brain activity in individuals with autism and in TD participants across slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and slow-3 (0.073-0.1 Hz) frequency bands. The diagnosis-by-age interaction effect in the whole brain voxels in autism and TD groups was investigated. Autism individuals showed significantly higher ALFF in the dorsal striatum in childhood (Caudate cluster: t=3.626, P=0.001; Putamen cluster: t=2.839, P=0.007) and remarkably lower ALFF in the dorsal striatum in adulthood (Caudate cluster: t=-2.198, P=0.038; Putamen cluster: t=-2.314, P=0.030) relative to TD, while no significant differences were observed in adolescence (all P>0.05). In addition, abnormal ALFF amplitudes were specific to the slow-4 (0.027-0.073 Hz) frequency band in the clusters above. The current study indicated abnormal development patterns in the spontaneous activity of the dorsal striatum in autism and highlighted the potential role of the slow-4 frequency band in the pathology of autism. Also, the potential brain mechanism of autism was revealed, suggesting that autism-related variations should be investigated in a specific frequency.


Surgical exclusion of unruptured middle cerebral artery aneurysms: experience of 126 cases.
A group of 126 surgical patients with 143 unruptured MCA aneurysms was evaluated in order to determine the risks of treatment and possible adjuncts for safer surgery. The precise location and size of the aneurysms were determined in each case; 21 aneurysms were located on the M1 tract, 109 on the main division - which consisted of more than two branches in 10 cases and was proximally located in 12 cases - and 13 were distal; 36 aneurysms were small (<7 mm), 90 standard, and 17 large or giant (>15 mm); 45 patients harbored multiple aneurysms (12 on the ipsilateral MCA). The aneurysms were excluded by clip in most cases, with the assistance of intraoperative flowmetry in 78 patients. Temporary proximal vessel occlusion was used in 57 patients (>10 min in 8 cases), without significant effects on radiological or clinical outcome. After surgery, newly occurring minor deficits were observed in 5 patients and significant deficits in 4; one patient died from an intractable coagulopathy. The low rate (3.9 %) of unfavorable results (modified Rankin Score > 2) linked to surgery justifies serious consideration for treatment in these patients, especially when facing the high disability rate after the rupture of aneurysms in this anatomical location.


Proteomic analysis of intra-arterial thrombus secretions reveals a negative association of clusterin and thrombospondin-1 with abdominal aortic aneurysm.
Abdominal aortic aneurysm (AAA) is usually accompanied by the formation of a large volume of intra-luminal thrombus (ILT). ILT-derived proteins have been suggested as circulating markers for AAA. We conducted a proteomic study screening whole and hexapeptide ligand library (HLL) treated ILT explant secretions to identify potential ILT-derived markers for AAA. Unfractionated and HLL-treated ILT secretions from 3 AAA patients were analysed in parallel using liquid chromatography tandem mass spectrometry (LC-MS/MS). In silico analyses were employed to identify proteins with biomarker potential. Proteomic findings were validated by measuring serum concentrations of 2 representative ILT proteins in 313 AAA patients and 690 controls. A total of 150 proteins were identified from thrombus conditioned media; HLL treatment enabled the detection of 53 previously unseen polypeptides. Gene ontology analysis revealed high representation of platelet-secreted proteins. Thrombospondin-1 (TSP-1) and clusterin were selected for further assessment. Serum TSP-1 and clusterin were negatively associated with AAA after adjusting for other risk factors. Odds ratio and 95% confidence intervals were 0.62, 0.41-0.94, and 0.50, 0.33-0.75, for men with serum TSP-1 and clusterin in the fourth compared to first quartiles, respectively. This proteomic analysis has identified a group of proteins concentrated in AAA ILT. Assessment of circulating concentrations of two representative polypeptides suggests for the first time that the ILT selectively sequesters proteins rather than actively releasing them. Further work is required to assess the mechanisms underpinning this observation and the associated clinical implications.


The link between fast food and the obesity epidemic.
Over thirty percent of adults are obese and over fifteen percent of children are considered obese. RESEARCH STUDY: Fat, sugar, and cholesterol have addictive qualities similar to the drug nicotine.


Valuing shifts in the distribution of visibility in national parks and wilderness areas in the United States.
Environmental regulations often have the objective of eliminating the lower tail of an index of environmental quality. That part of the distribution of environmental quality moves somewhere above a threshold and where in the original distribution it moves is a function of the control strategy chosen. This paper provides an approach for estimating the economic benefits of different distributional changes as the worst environmental conditions are removed. The proposed approach is illustrated by examining shifts in visibility at Class I visibility areas (National Parks and wilderness areas) that would occur with implementation of the U.S. Environmental Protection Agency's Regional Haze Program. In this application we show that people value shifts in the distribution of visibility and place a higher value on the removal of a low visibility day than on the addition of a high visibility day. We found that respondents would pay about $120 per year in the Southeast U.S. and about $80 per year in the Southwest U.S. for improvement programs that remove the 20% worst visibility days.


Induced fusion of female gametes and embryonic cells.
Investigations in which the method of induced cell fusion was used in studying the oocyte maturation, fertilization and early embryogenesis of animals have been reviewed on the basis of published data and the authors' experience. The problems of developing the method of induced cell fusion, its combination with other methods (microsurgery, cell fragmentation, etc.) and the perspectives of its use in embryology are discussed.


A systematic review and meta-analysis on the treatment of liver hydatid cyst: Comparing laparoscopic and open surgeries.
There is an academic debate regarding surgical interventions for liver hydatid cyst disease. The purpose of the current systematic review and meta-analysis study was to analyse the pros and cons of open surgery and laparoscopic techniques, considering the outcomes of liver hydatid cysts. Descriptive Boolean queries were used to search PubMed and Scopus for articles published between January 2000 and December 2016 to evaluate the outcomes of liver hydatid cyst in terms of mortality, post-operative complications, cure rate and recurrences. The data related to the four outcomes of liver hydatid cyst were extracted, assessed and then used as their corresponding effect sizes in the meta-analysis process. Six studies totally consisting of 1028 patients [open surgery group=816 (+7 converted to lap) and laparoscopic group=212] were analysed. In this meta-analysis study, random effects models of outcomes (i.e. post-operative complications, mortalities, recurrences and cure rate) of the two procedures were OR=0.852, LL=0.469, UL=1.546, Z=-0.526, p=0.599 (for post-operative complications); OR=0.849, LL=0.141, UL=5.105, Z=-0.179, p=0.858 (for mortality); OR=0.903, LL=0.166, UL=4.906, Z=-0.119, p=0.906 (for recurrence); and OR=0.459, LL=0.129, UL=1.637, Z=-1.201, p=0.230 (for cure rate). Meta-analysis and illustrated forest plots showed that there are no superiorities between the two approaches. The results of heterogeneity tests of the above mentioned outcomes were Q=8.083, df=5, p=0.152, I2=38.142% for post-operative complications; Q=0.127, df=2, p=0.938, I2=0% for mortality; Q=4.984, df=2, p=0.083, I2=59.874% for recurrence; and Q=10.639, df=5, p=0.059, I2=53.001% for cure rate. The results of regression tests based on Egger's, smoothed variance based on Egger (SVE) and smoothed variance based on Thomson (SVT) showed that the p values are not significant, and there are neither significant statistical differences nor publication bias between the outcomes of the two treatment procedures. The results show no promising trends towards advantages of open versus laparoscopic surgeries in the treatment of liver hydatid cyst. However, informative measurement values for comparing these surgeries could be derived for complications, recurrence, mortality and cure rates. Furthermore, all three tests, namely Egger's, SVE and SVT regression models, were used to assess publication bias and showed no evidence for the existence of publication bias.