Higher baseline resting metabolic rate is associated with 1-year frailty decline among older adults residing in an urban area.

BACKGROUND: Dysregulated energy metabolism is one hypothesized mechanism underlying frailty. Resting energy expenditure, as reflected by resting metabolic rate (RMR), makes up the largest component of total energy expenditure. Prior work relating RMR to frailty has largely been done in cross section with mixed results. We investigated whether and how RMR related to 1-year frailty change while adjusting for body composition. METHODS: N = 116 urban, predominantly African-American older adults were recruited between 2011 and 2019. One-year frailty phenotype (0-5) was regressed on baseline RMR, frailty phenotype, demographics and body composition (DEXA) in an ordinal logistic regression model. Multimorbidity (Charlson comorbidity scale, polypharmacy) and cognitive function (Montreal Cognitive Assessment) were separately added to the model to assess for change to the RMR-frailty relationship. The model was then stratified by baseline frailty status (non-frail, pre-frail) to explore differential RMR effects across frailty. RESULTS: Higher baseline RMR was associated with worse 1-year frailty (odds ratio = 1.006 for each kcal/day, p = 0.001) independent of baseline frailty, demographics, and body composition. Lower fat-free mass (odds ratio = 0.88 per kg mass, p = 0.008) was independently associated with worse 1-year frailty scores. Neither multimorbidity nor cognitive function altered these relationships. The associations between worse 1-year frailty and higher baseline RMR (odds ratio = 1.009, p < 0.001) and lower baseline fat-free mass (odds ratio = 0.81, p = 0.006) were strongest among those who were pre-frail at baseline. DISCUSSION: We are among the first to relate RMR to 1-year change in frailty scores. Those with higher baseline RMR and lower fat-free mass had worse 1-year frailty scores, but these relationships were strongest among adults who were pre-frail at baseline. These relationships were not explained by chronic disease or impaired cognition. These results provide new evidence suggesting higher resting energy expenditure is associated with accelerate frailty decline.

A simulação da biomassa de aveia por elementos climáticos, nitrogênio e regulador de crescimento / The simulation of the oat biomass by climatic elements, nitrogen and growth regulator

A produção de biomassa de aveia voltada à elaboração de silagem de qualidade é dependente de elementos climáticos e nitrogênio sem ocorrência de acamamento. O objetivo do presente estudo é a definição da dose ideal do regulador de crescimento que possibilite, no máximo, 5% de acamamento de plantas de aveia, bem como a identificação das variáveis potenciais para composição do modelo de regressão linear múltipla com simulação da produtividade de biomassa à elaboração de silagem nas condições de uso do regulador, em reduzida, alta e muito alta fertilização com nitrogênio. O estudo foi conduzido em 2013, 2014 e 2015, em delineamento de blocos ao acaso, com quatro repetições em esquema fatorial 4x3, para doses de regulador (0, 200, 400 e 600mL ha-1) e doses de nitrogênio (30, 90 e 150kg ha-1), respectivamente. A dose de 495mL ha-1 de regulador se mostra eficiente na redução do acamamento de plantas de aveia em condição de reduzida, alta e muito alta fertilização com nitrogênio. A soma térmica, a precipitação, a radiação, a dose de regulador e o nitrogênio qualificam a composição do modelo de regressão linear múltipla, tornando eficiente a simulação da produtividade de biomassa da aveia para silagem ao longo do ciclo.(AU)

The production of oat biomass focused on the development of quality silage is dependent on climatic elements and nitrogen without lodging occurrence. The objective of the study is to define the optimal dose of growth regulator that allows a maximum of 5% oat plant lodging and identify potential variables for composition of multiple linear regression model with productivity simulation of biomass to the preparation of silage in the conditions of low, high and very high fertilization with nitrogen. The study was conducted in 2013, 2014, and 2015 in the randomized block design with four replications in a factorial 4x3, for regulator doses (0, 200, 400 and 600ml ha-1) and nitrogen doses (30, 90 and 150kg ha-1), respectively. The dose of 495mL ha-1 regulator is efficient in reducing the oat plant lodging in condition reduced, high, and very high fertilization with nitrogen. Thermal time, precipitation, radiation, regulator dose and nitrogen dose qualify the composition of the multiple linear regression model, making efficient the biomass oat productivity simulation for silage over the cycle.(AU)

[Spincter preservation after selective chemoradiotherapy of rectal cancer. Interim results of the OCUM study]. / Spinktererhalt nach selektiver Radiochemotherapie des Rektumkarzinoms. Zwischenergebnisse der OCUM-Studie.

BACKGROUND: In a prospective multicenter observational study (OCUM) neoadjuvant chemoradiotherapy (nRCT) was selectively administered depending on the risk of local recurrence and based on the distance between tumor and mesorectal fascia in pretherapeutic high-resolution magnetic resonance imaging (MRI). OBJECTIVE: Frequency and quality of abdominoperineal excision (APE) and sphincter preserving operations. PATIENTS AND METHODS: Of 642 patients treated in 13 hospitals 389 received surgery alone and 253 nRCT followed by surgery. By univariate and multivariate analysis risk factors for APE were determined. Quality parameters were the quality grade of mesorectal excision, the pathohistological involvement of the circumferential resection margin and intraoperative local dissemination of tumor cells. RESULTS AND DISCUSSION: In 12.8 % of the patients APE was performed. Independent risk factors for APE were tumor location in the lower third of the rectum and the individual hospitals, where APE varied between 0 and 32 %. This variation was chiefly caused by the different case mix. Hospitals with a high APE rate (> 30 %) treated significantly more patients with very low lying carcinomas (< 3 cm above the anal verge) and more advanced tumors. The median height of the tumor in cases of APE was nearly equal in all participating hospitals. Independent on the number of cases the quality of rectal surgery was high. Within the patient groups of primary surgery and nRCT the oncological quality parameter did not significantly differ between sphincter preservation and APE. As far as sphincter preservation is concerned the results justify a selective application of nRCT in patients with rectal carcinoma. The long-term results still have to be awaited.

Response of the coagulation system after application of hemostatic dressings in an animal model.

The objective of this study was to determine the response of hemostatic dressings. Coagulation and fibrinolytic systems, red blood cell parameters, platelet and leukocyte counts were evaluated after the application of hemostatic dressings: QuikClot, Chitoauze and Celox gauze. The experiment was performed on ten pigs.

Analysis of the results and long-term follow-up of second-look laparotomy in advanced ovarian cancer.

OBJECTIVE: The goal of the study was to analyze results of 171 second-look laparotomy and compare survival of patients with advanced ovarian cancer depending on SLL results. RESULTS: We obtained the following results: complete pathologic response (CPR)--56.2% (96 patients), microscopic disease (R(micro))--12.8% (22 patients), macroscopic disease (R(marco))--31% (53 patients). In patients with negative SLL results disease recurrence was diagnosed in 38.5%. We compared survival in separate groups of patients depending on SLL results: no difference between the CPR group and R(micro) group. Significantly longer survival of patients in the R(micro) group was found compared to patients with recurrence after negative SLL. There were no differences between the group with recurrence after negative SLL and the R(macro) group. CONCLUSIONS: An important observation is that the survival rate in patients with recurrence after negative SLL was significantly lower compared to patients with microscopic disease. The probable explanation for favorable prognosis in the group with microscopic disease was early administration of chemotherapy after SLL.

Combination of intraperitoneal hyperthermic perfusion chemotherapy (IHPC) with intraperitoneal chemotherapy as a treatment modality for persistent ovarian cancer.

Persistent minimal residual disease diagnosed after the first line of chemotherapy during second-look surgery can be an indication for intraperitoneal chemotherapy. Another treatment option is intraperitoneal hyperthermic perfusion chemotherapy (IHPC) where the drug is administrated into the peritoneal cavity with the use of extracorporeal closed circuit perfusate circulation at a temperature of 41-42 degrees C. We have started to perform, as a second-line treatment, a combination of one IHPC procedure and four cycles of standard intraperitoneal chemotherapy. In a patient who had previously undergone three different chemotherapy regimens, stabilization of the disease was achieved. In our opinion combining the IHPC procedure with intraperitoneal chemotherapy can be valuable in patients with small volume residual tumor.

Sentinel node identification in cervical cancer patients undergoing transperitoneal radical hysterectomy: a study of 100 cases.

We investigated the feasibility of sentinel lymph node (SN) identification using radioisotopic lymphatic mapping with technetium-99m-labeled nanocolloid and blue-dye injection in 100 patients with early cervical cancer (FIGO stage IB1 in 58, IB2 in 18, and IIA in 24) undergoing radical hysterectomy with pelvic lymphadenectomy. At least one SN was found in 84% on one side and in 66% on both sides. The sentinel detection rates according to the stages were as follows: 96.6% in IB1, 66.7% in IB2, and 62.5% in IIA with at least one SN on one side, and 86.2% in IB1, 38.9% in IB2, and 37.5% in IIA with at least one SN on both sides. Successful identification of at least one SN was less likely in patients with tumors >2 cm (54% of SN) compared with those with tumors

The role of pelvic exenteration for treatment of pelvic malignancy--a nine-year experience.

Pelvic exenteration offers the last chance for some women with gynecological and rectal malignancy. A series of 23 patients who underwent pelvic exenteration for local advanced gynecological and rectal malignancies between 1996 and 2004 were retrospectively reviewed. The exenteration was performed because of vulvar cancer in 14 patients and other pelvic malignancies in nine cases: rectal cancer in four cases, in three cases cervical cancer, in one case ovarian cancer and in one case uterine sarcoma. Nine patients developed major complications of the operative field involving the urinary tract or the wound. Early complications included massive bleeding from the sacral plexus in two cases (one patient died during surgery), acute respiratory distress syndrome (ARDS) in one case and thrombophlebitis in one case. Urinary incontinence was observed in two women as a late complication. Only one patient had a complication connected with the gastrointestinal tract. Twenty-two patients were followed-up. In the group of patients with vulvar cancer five women died after 4-29 months because of recurrence of disease. The nine surviving patients are still being followed-up and are without disease; survival time ranges from 6-74 months. In the group of patients with other malignancies four women died.

Coronavirus transcription: a perspective.

At the VIth International Symposium on Corona and Related Viruses held in Quebec, Canada in 1994 we presented a new model for coronavirus transcription to explain how subgenome-length minus strands, which are used as templates for the synthesis of subgenomic mRNAs, might arise by a process involving discontinuous RNA synthesis. The old model explaining subgenomic mRNA synthesis, which was called leader-primed transcription, was based on erroneous evidence that only genome-length negative strands were present in replicative intermediates. To explain the discovery of subgenome-length minus strands, a related model, called the replicon model, was proposed: The subgenomic mRNAs would be produced initially by leader-primed transcription and then replicated into minus-strand templates that would in turn be transcribed into subgenomic mRNAs. We review the experimental evidence that led us to formulate a third model proposing that the discontinuous event in coronavirus RNA synthesis occurs during minus strand synthesis. With our model the genome is copied both continuously to produce minus-strand templates for genome RNA synthesis and discontinuously to produce minus-strand templates for subgenomic mRNA synthesis, and the subgenomic mRNAs do not function as templates for minus strand synthesis, only the genome does.

Negative strand RNA synthesis by temperature-sensitive mutants of mouse hepatitis virus.

Mutants of the A59 strain of mouse hepatitis virus (MHV) were studied to determine the effects of temperature shift on negative and positive strand RNA synthesis. Mutant LA 9 was originally reported to have a selective temperature sensitive defect in negative strand synthesis. We found that this mutant continued to synthesize negative strands for at least one hour after temperature shift. LA 6 was found to possess a temperature sensitive defect in negative strand synthesis. Following temperature shift, negative strand synthesis rapidly declined. The effect of temperature shift on negative strand synthesis by LA 6 was similar to the effect of cycloheximide treatment of the parental A59 virus. Temperature shift of Alb 16 infected cells did not stop negative strand synthesis but did prevent a corresponding rise in the rate of positive strand synthesis. Therefore, we suggest that Alb 16 is a conversion mutant because it cannot convert newly synthesized negative strands into templates for positive strand synthesis at the nonpermissive temperature.

A new model for coronavirus transcription.

Coronaviruses contain an unusually long (27-32,000 ribonucleotide) positive sense RNA genome that is polyadenylated at the 3' end and capped at the 5' end. In addition to the genome, infected cells contain subgenomic mRNAs that form a 3' co-terminal nested set with the genome. In addition to their common 3' ends, the genome and the subgenomic mRNAs contain an identical 5' leader sequence. The transcription mechanism that coronaviruses use to produce subgenomic mRNA is not known and has been the subject of speculation since sequencing of the subgenomic mRNAs showed they must arise by discontinuous transcription. The current model called leader-primed transcription has subgenomic mRNAs transcribed directly from genome-length negative strands. It was based on the failure to find in coronavirus infected cells subgenome-length negative strands or replication intermediates containing subgenome-length negative strands. Clearly, these structures exist in infected cells and are transcriptionally active. We proposed a new model for coronavirus transcription which we called 3' discontinuous extension of negative strands. This model predicts that subgenome-length negative strands would be derived directly by transcription using the genome RNA as a template. The subgenome-length templates would contain the common 5' leader sequence and serve as templates for the production of subgenomic mRNAs. Our findings include showing that: 1. Replication intermediates (RIs) containing subgenome-length RNA exist in infected cells and are separable from RIs with genome-length templates. The RFs with subgenome-length templates are not derived by RNase treatment of RIs with genome-length templates. 2. The subgenome-length negative strands are formed early in infection when RIs are accumulating and the rate of viral RNA synthesis is increasing exponentially. 3. Subgenome-length negative strands contain at their 3' ends a complementary copy of the 72 nucleotide leader RNA that is found in the genome only at their 5' end. 4. RIs with subgenomic templates serve immediately as templates for transcription of subgenomic mRNAs. Because subgenomic mRNAs are not replicated, i.e., copied into negative strands that in turn are used as templates for subgenomic mRNA synthesis, we propose that the subgenome-length negative strands must arise directly by transcription of the genome and acquire their common 3' anti-leader sequence after polymerase jumping from the intergenic regions to the leader sequence at the 5' end of the genome. This would make negative strand synthesis discontinuous and subgenomic mRNA synthesis continuous, which is the opposite of what was proposed in the leader primed model.

Selection in persistently infected murine cells of an MHV-A59 variant with extended host range.

Murine coronavirus MHV-A59 normally infects only murine cells in vitro and causes transmissible infection only in mice. In the 17 C1 1 line of murine cells, the receptor for MHV-A59 is MHVR, a biliary glycoprotein in the carcinoembryonic antigen (CEA) family of glycoproteins. We found that virus released from the 600th passage of 17 C1 1 cells persistently infected with MHV-A59 (MHV/pi600) replicated in hamster (BHK-21) cells. The virus was passaged and plaque-purified in BHK-21 cells, yielding the MHV/BHK strain. Because murine cells persistently infected with MHV-A59 express a markedly reduced level of MHVR (Sawicki, et al., 1995), we tested whether virus with altered receptor interactions was selected in the persistently infected culture. Infection of 17 C1 1 cells by MHV-A59 can be blocked by treating the cells with anti-MHVR MAb-CC1, while infection by MHV/BHK was only partially blocked by MAb-CC1. MHV/BHK virus was also more resistant than wild-type MHV-A59 to neutralization by purified, recombinant, soluble MHVR glycoprotein (sMHVR). Cells in the persistently infected culture may also express reduced levels of and have altered interactions with some of the Bgp-related glycoproteins that can serve as alternative receptors for MHV-A59. Unlike the parental MHV-A59 which only infects murine cells, MHV/BHK virus was able to infect cell lines derived from mice, hamsters, rats, cats, cows, monkeys and humans. However, MHV/BHK was not able to infect all mammalian species, because a pig (ST) cell line and a dog cell line (MDCK I) were not susceptible to infection. MHV/pi600 and MHV/BHK replicated in murine cells more slowly than MHV-A59 and formed smaller plaques. Thus, in the persistently infected murine cells which expressed a markedly reduced level of MHVR, virus variants were selected that have altered interactions with MHVR and an extended host range. In vivo, in mice infected with coronavirus, virus variants with altered receptor recognition and extended host range might be selected in tissues that have low levels of receptors. Depending upon the tissue in which such a virus variant was selected, it might be shed from the infected animal or eaten by a predator, thus presenting a possible means for initiating the transition of a variant virus into a new host as a model for an emerging virus disease.

Regulation of alphavirus 26S mRNA transcription by replicase component nsP2.

Semliki Forest virus (SFV) mutant ts4 has a reversible temperature-sensitive defect in the synthesis the subgenomic 26S mRNA. The viral nonstructural protein nsP2 was identified as a regulator of 26S synthesis by transferring nsP2 coding sequences from ts4 into the infectious SFV cDNA clone (SFoto) to create SFots4. Sequencing identified the causal mutation as C4038U, predicting the amino acid change M781T in nsP2. A revertant was isolated in which a back mutation of U to C restored the wild-type phenotype. Compared to Sindbis virus nsP2 mutants ts15, ts17, ts18, ts24 and ts133, which also exhibit temperature-sensitive 26S RNA synthesis, ts4 and SFots4 reduced 26S RNA synthesis faster and to lower levels after temperature shift. Under these conditions, ts4 and SFots4 also displayed complete conversion of RFII+RFIII into RFI and reactivated minus-strand synthesis. After shift to 39 degrees C, ts4 nsP2 was released from a crude RNA polymerase preparation consisting of membranes sedimenting at 15,000 g (P15) and the remaining, unreleased nsP2 was capable of being cross-linked in almost equimolar ratio with nsP1 and nsP3. This supports the hypothesis that nsP2 binds directly or undirectly to the promoter for 26S RNA and that it is also an essential component of the viral replicase synthesizing 42S RNA plus strands. Only the former activity is temperature-sensitive in ts4 mutant.

Baby boom. American anti-abortion politics blocks family planning funding around the world.

PIP: American anti-abortion politics is blocking family planning (FP) funding around the world. US Representative Chris Smith, a Republican of New Jersey, attempted to amend a proposal that would require health-care providers of federal workers who cover prescription drugs to also pay for prescribed contraceptives. Smith's amendment would have exempted any contraceptive that inhibits implantation. This action was defeated but clearly revealed that this anti-abortion politician's agenda is also anti-FP. The right-wing has hampered Clinton administration efforts to support reproductive rights. There is a link between FP and the survival of the planet from an environmentalist point of view that recognizes the extreme danger of the resource depletion attendant upon overpopulation. The Vatican's opposition to reproductive rights has resulted in serious restrictions on the delivery of reproductive health care in cases where public hospitals have merged with Roman Catholic health corporations. The population problem is "fixable" but efforts to do so remain deadlocked by a vocal minority of conservatives.^ieng

The murine coronavirus mouse hepatitis virus strain A59 from persistently infected murine cells exhibits an extended host range.

In murine 17 Cl 1 cells persistently infected with murine coronavirus mouse hepatitis virus strain A59 (MHV-A59), expression of the virus receptor glycoprotein MHVR was markedly reduced (S. G. Sawicki, J. H. Lu, and K. V. Holmes, J. Virol. 69:5535-5543, 1995). Virus isolated from passage 600 of the persistently infected cells made smaller plaques on 17 Cl 1 cells than did MHV-A59. Unlike the parental MHV-A59, this variant virus also infected the BHK-21 (BHK) line of hamster cells. Virus plaque purified on BHK cells (MHV/BHK) grew more slowly in murine cells than did MHV-A59, and the rate of viral RNA synthesis was lower and the development of the viral nucleocapsid (N) protein was slower than those of MHV-A59. MHV/BHK was 100-fold more resistant to neutralization with the purified soluble recombinant MHV receptor glycoprotein (sMHVR) than was MHV-A59. Pretreatment of 17 Cl 1 cells with anti-MHVR monoclonal antibody CC1 protected the cells from infection with MHV-A59 but only partially protected them from infection with MHV/BHK. Thus, although MHV/BHK could still utilize MHVR as a receptor, its interactions with the receptor were significantly different from those of MHV-A59. To determine whether a hemagglutinin esterase (HE) glycoprotein that could bind the virions to 9-O-acetylated neuraminic acid moieties on the cell surface was expressed by MHV/BHK, an in situ esterase assay was used. No expression of HE activity was detected in 17 Cl 1 cells infected with MHV/BHK, suggesting that this virus, like MHV-A59, bound to cell membranes via its S glycoprotein. MHV/BHK was able to infect cell lines from many mammalian species, including murine (17 Cl 1), hamster (BHK), feline (Fcwf), bovine (MDBK), rat (RIE), monkey (Vero), and human (L132 and HeLa) cell lines. MHV/BHK could not infect dog kidney (MDCK I) or swine testis (ST) cell lines. Thus, in persistently infected murine cell lines that express very low levels of virus receptor MHVR and which also have and may express alternative virus receptors of lesser efficiency, there is a strong selective advantage for virus with altered interactions with receptor (D. S. Chen, M. Asanaka, F. S. Chen, J. E. Shively, and M. M. C. Lai, J. Virol. 71:1688-1691, 1997; D. S. Chen, M. Asanaka, K. Yokomori, F.-I. Wang, S. B. Hwang, H.-P. Li, and M. M. C. Lai, Proc. Natl. Acad. Sci. USA 92:12095-12099, 1995; P. Nedellec, G. S. Dveksler, E. Daniels, C. Turbide, B. Chow, A. A. Basile, K. V. Holmes, and N. Beauchemin, J. Virol. 68:4525-4537, 1994). Possibly, in coronavirus-infected animals, replication of the virus in tissues that express low levels of receptor might also select viruses with altered receptor recognition and extended host range.