Safety, feasibility, and effect of an enhanced nutritional support pathway including extended preoperative and home enteral nutrition in patients undergoing enhanced recovery after esophagectomy: a pilot randomized clinical trial.

The aims of this pilot study are to evaluate the feasibility, safety, and effectiveness of conducting an enhanced nutritional support pathway including extended preoperative nutritional support and one month home enteral nutrition (HEN) for patients who underwent enhanced recovery after esophagectomy. We implemented extended preoperative nutritional support and one month HEN after discharge for patients randomized into an enhanced nutrition group and implemented standard nutritional support for patients randomized into a conventional nutrition group. Except the nutritional support program, both group patients underwent the same standardized enhanced recovery after surgery programs of esophagectomy based on published guidelines. Patients were assessed at preoperative day, postoperative day 7 (POD7), and POD30 for perioperative outcomes and nutritional status. To facilitate the determination of an effect size for subsequent appropriately powered randomized clinical trials and assess the effectiveness, the primary outcome we chose was the weight change before and after esophagectomy. Other outcomes including body mass index (BMI), lean body mass (LBM), appendicular skeletal muscle mass index (ASMI), nutrition-related complications, and quality of life (QoL) were also analyzed. The intention-to-treat analysis of the 50 randomized patients showed that there was no significant difference in baseline characteristics. The weight (-2.03 ± 2.28 kg vs. -4.05 ± 3.13 kg, P = 0.012), BMI (-0.73 ± 0.79 kg/m2 vs. -1.48 ± 1.11 kg/m2, P = 0.008), and ASMI (-1.10 ± 0.37 kg/m2 vs. -1.60 ± 0.66 kg/m2, P = 0.010) loss of patients in the enhanced nutrition group were obviously decreased compared to the conventional nutrition group at POD30. In particular, LBM (48.90 ± 9.69 kg vs. 41.96 ± 9.37 kg, p = 0.031) and ASMI (7.56 ± 1.07 kg/m2 vs. 6.50 ± 0.97 kg/m2, P = 0.003) in the enhanced nutrition group were significantly higher compared to the conventional nutrition group at POD30, despite no significant change between pre- and postoperation. In addition, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scores revealed that enhanced nutritional support improved the QoL of patients in physical function (75.13 ± 9.72 vs. 68.33 ± 7.68, P = 0.009) and fatigue symptom (42.27 ± 9.93 vs. 49.07 ± 11.33, P = 0.028) compared to conventional nutritional support. This pilot study demonstrated that an enhanced nutritional support pathway including extended preoperative nutritional support and HEN was feasible, safe, and might be beneficial to patients who underwent enhanced recovery after esophagectomy. An appropriately powered trial is warranted to confirm the efficacy of this approach.

[Characterization of N-linked glycosylation sites on envelope proteins of simian/human immunodeficiency virus in peripheral blood of Chinese rhesus macaques during acute infection].

Objective: To investigate the number and distribution of N-linked glycosylation sites of simian/human immunodeficiency virus envelope proteins(SHIVSF162P3)and SHIV transmission. Methods: Two female adult Chinese rhesus macaques(4 years old)were intravenously inoculated with 300 TCID50 SHIVSF162P3. The macaques weighed 4 and 5 kg and were identified as Rh1 and Rh2. We collected plasma samples at days 3, 7, 10, 14, 17, 21, 24, 28, 35, 42, 49, 56, 63, 70 and 77 post-challenge. Subsequently, we monitored plasma viral load by real-time PCR after viral RNA isolation and cDNA synthesis. We amplified the full-length envelope gene by single genome amplification(SGA)at days 7, 14, 28 and 77. BioEdit, MEGA, and the HIV Databases were used to analyze envelope sequences. Sequence diversity and N-linked glycosylation sites were compared between virus stock and plasma viruses of the two macaques. Results: A total of 55 env sequences were obtained from virus stock and their average pairwise distances were(0.166 6± 0.096 3)%. Viral loads peaked at 7.68 and 7.49 log10 copies/ml at day 10 and reached the set point at day 42(4.27 and 4.81 log10 copies/ml). The percentages of envelope sequences containing 25 potential N-linked glycosylation sites(PNGSs)were 83%(20/24)and 94%(29/31)in Rh1 and Rh2, respectively, at day 7; these were significantly higher than the proportion in SHIVSF162P3 stock(49%(27/55)). Viral diversity after infection increased with time whereas the proportion of sequences containing 25 PNGSs decreased and sequences containing 27 PNGSs gradually increased. In Rh1, the percentage of sequences containing 27 PNGSs increased to 29% at day 28 and reached 35% at day 77 in Rh2. By analyzing the number of PNGSs in the V1-V5 regions, we found that PNGS variation mainly occurred in the V4 loop. Compared with sequences containing 27 PNGSs, a seven amino acid(TWNNTIG)deletion was found in the V4 loop, which resulted in a loss of two PNGSs at positions 392 and 396. Conclusion: Low glycosylation of the SHIVSF162P3 V4 loop may facilitate spread of the SHIV virus whereas viruses with highly glycosylated V4 loops showed replication advantages after infection.

High-efficiency diode-pumped actively Q-switched ceramic Nd:YAG/BaWO4 Raman laser operating at 1666 nm.

A diode-pumped actively Q-switched Raman laser employing BaWO4 as the Raman active medium and a ceramic Nd:YAG laser operating at 1444 nm as the pump source is demonstrated. The first-Stokes-Raman generation at 1666 nm is achieved. With a pump power of 20.3 W and pulse repetition frequency rate of 5 kHz, a maximum output power of 1.21 W is obtained, which is the highest output power for a 1.6 µm Raman laser. The corresponding optical-to-optical conversion efficiency is 6%; the pulse energy and peak power are 242 µJ and 8.96 kW, respectively.

High efficiency Nd:YAG ceramic eye-safe laser operating at 1442.8 nm.

We report on a diode-pumped Nd:YAG ceramic laser operating at 1442.8 nm for the first time. In our experiment, two different Nd:YAG ceramics with the Nd-doped concentrations of 1.0 and 0.6 at. % and a Nd:YAG with the Nd-doped concentration of 1.0 at. % were used as the laser gain mediums, respectively. At a pump power of 20.7 W, a maximum output power of up to 3.96 W with optical-to-optical efficiency of up to 19.1% was obtained by using the 1.0 at. % Nd-doped ceramic as the laser gain medium. To the best of our knowledge, this is the highest output power of a LD-pumped 1.44 µm Nd:YAG ceramic laser and the highest optical-to-optical efficiency of a LD-pumped 1.44 µm Nd-doped crystal laser.

TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells.

BACKGROUND: The full mechanism of action of isotretinoin [13-cis retinoic acid (13-cis RA)] in treating acne is unknown. 13-cis RA induces key genes in sebocytes that are involved in apoptosis, including Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL). OBJECTIVES: In this study, we investigated the role of 13-cis RA-induced TRAIL within SEB-1 sebocytes. METHODS: Using 13-cis RA and recombinant human TRAIL (rhTRAIL) protein, we assessed induction of TRAIL and apoptosis in SEB-1 sebocytes, normal keratinocytes and patient skin biopsies. RESULTS: Treatment with rhTRAIL protein increased TUNEL-positive staining in SEB-1 sebocytes. TRAIL siRNA significantly decreased the percentage of TUNEL-positive SEB-1 sebocytes in response to 13-cis RA treatment. Furthermore, TRAIL expression increased in the skin of patients with acne after 1 week of isotretinoin therapy compared with baseline. TRAIL expression localized within sebaceous glands. Unlike sebocytes, TRAIL protein expression was not increased in normal human epidermal keratinocytes in response to 13-cis RA, nor did rhTRAIL induce apoptosis in keratinocytes, suggesting that TRAIL is key in the sebocyte-specific apoptotic effects of 13-cis RA. CONCLUSIONS: Taken together, our data suggest that TRAIL, like the neutrophil gelatinase-associated lipocalin, is involved in mediating 13-cis RA apoptosis of sebocytes.

Isotretinoin increases skin-surface levels of neutrophil gelatinase-associated lipocalin in patients treated for severe acne.

BACKGROUND: A clear-cut need exists for safe and effective alternatives to the use of isotretinoin in severe acne. Lack of data regarding the specifics of isotretinoin's mechanism of action has hampered progress in this area. Recently, the protein neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a mediator of the apoptotic effect of isotretinoin on sebocytes. OBJECTIVES: To establish further the clinical relevance of NGAL and to elucidate the factors that induce NGAL expression in sebocytes. METHODS: Methods were developed to isolate and quantify skin-surface levels of NGAL from normal subjects and patients with acne undergoing treatment with isotretinoin. RESULTS: Patients with acne were found to have higher skin levels of NGAL compared with normal subjects. Studies in SEB-1 sebocytes indicate that NGAL expression is increased in response to Propionibacterium acnes and interleukin (IL)-1ß. In patients, isotretinoin increases NGAL levels by 2·4-fold on the skin surface and this increase precedes decreases in sebum and P. acnes counts. CONCLUSIONS: These data support the hypothesis that NGAL is an important mediator of the early effects of isotretinoin on the sebaceous glands and provide insights into the mechanisms that regulate NGAL expression in the skin.

Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study.

Deep brain stimulation (DBS) of the thalamic centromedian/parafascicular (CM-Pf) complex has been reported as a promising treatment for patients with severe, treatment-resistant Tourette syndrome (TS). In this study, safety and clinical outcomes of bilateral thalamic CM-Pf DBS were reviewed in a series of 12 consecutive patients with medically refractory TS, 11 of whom met the criteria of postsurgical follow-up at our institution for at least 2 months. Five patients were followed for a year or longer. Consistent with many patients with TS, all patients had psychiatric comorbidities. Tic severity and frequency were measured by using the Yale Global Tic Severity Scale (YGTSS) over time (average, 26 months) in 10 subjects. One patient was tested at 2-week follow-up only and thus was excluded from group YGTSS analysis. Final YGTSS scores differed significantly from the preoperative baseline score. The average (n=10) improvement relative to baseline in the total score was 54% (95% CI, 37-70); average improvement relative to baseline in the YGTSS Motor tic, Phonic tic, and Impairment subtests was 46% (95% CI, 34-64), 52% (95% CI, 34-72), and 59% (95% CI, 39-78), respectively. There were no intraoperative complications. After surgery, 1 subject underwent wound revision because of a scalp erosion and wound infection; the implanted DBS system was successfully salvaged with surgical revision and combined antibiotic therapy. Stimulation-induced adverse effects did not prevent the use of the DBS system, although 1 subject is undergoing a trial period with the stimulator off. This surgical series adds to the literature on CM-Pf DBS and supports its use as an effective and safe therapeutic option for severe refractory TS.

The melanocortin 5 receptor is expressed in human sebaceous glands and rat preputial cells.

Melanocortins regulate pigmentation, adrenal hormone secretion, immune functions, lipid metabolism, and feeding behaviors in rodents. These peptides include adrenocorticotrophic hormone, melanocyte stimulating hormone, beta-lipotrophin, and the endorphins. Lipid metabolism in sebaceous glands and preputial glands of rodents is regulated by alpha-melanocyte stimulating hormone, the major agonist for melanocortin receptors. Five melanocortin receptor subtypes have been identified that differ in their tissue localization and affinities for melanocortin ligands. Targeted disruption of the melanocortin 5 receptor in transgenic mice results in widespread dysfunction of exocrine glands, including a marked decrease in sebum production. A role for melanocortins in the modulation of human sebum production has not been established. The goal of this study is to determine which melanocortin receptors are expressed in human sebaceous glands. Messenger RNA was isolated from human sebaceous glands and the reverse transcriptase polymerase chain reaction was performed using primers specific for each of the melanocortin receptor subtypes. Transcripts were detected for the melanocortin 5 receptor. A polyclonal chicken antihuman antibody to the melanocortin 5 receptor localized to sebaceous glands, eccrine glands, hair follicles, and epidermis in human skin, rat skin, cultured human sebocytes, and rat preputial cells. Presence of the melanocortin 5 receptor protein in human sebaceous glands and rat preputial glands was further verified by Western blotting. These data support further investigation of the role of melanocortins in the regulation of human sebum production and support the use of the rat preputial system as an experimental model in sebaceous gland physiology.

[Observing cytoprotection of indomethacin on primary cultured hepatocytes of rats].

We observed previously that indomethacin induced hepatic protection against CCl4 and galactosamine in rats. In this work we further investigated this phenomenon on primary cultured rat hepatocytes. The results showed that cultured hepatocytes of rats pretreated with indomethacin in vivo still retained the ability resisting CCl4-induced cytotoxicity, as indicated by lower leakage of enzymes. However, cultured hepatocytes of normal rats treated with indomethacin in vitro had no obvious resistance to CCl4-induced cytotoxicity. The results suggest that indomethacin pretreatment in vivo enables hepatocytes to resist injury, which probably also needs participation of other factors.

[Influence of several Chinese drugs on the glycogen synthesizing function of primary cultured adult rat hepatocytes].

The influence of several Chinese drugs on the glycogen synthesizing function of normal and carbon tetrachloride-injured hepatocytes was investigated. Hepatocytes prepared from rats fasted for 16 h were incubated with 50 mmol/L glucose. Glycogen content was determined 30 and 90 min after incubation with normal and CCl4-injured cells, respectively. Insulin was used as positive control which increased glycogen content and the data coincided with that in the literature. The following results were obtained (1) Biphenyl-dimethyl-dicarboxylate (BDD) in 100 micrograms/ml concentration increased glycogen content of normal hepatocytes by 88%. It protected cells against CCl4-injury:BDD 10 micrograms/ml remarkably decreased CCl4-induced reduction of glycogen and 100 micrograms/ml showed complete protection. (2) Tremella poly-saccharide slightly increased glycogen content in normal cells, but in a concentration of 100 micrograms/ml it decreased CCl4-induced reduction of glycogen significantly. (3) Low concentration of norcatharidin (10 micrograms/ml) increased glycogen content of normal cells, but at 100 micrograms/ml concentration this effect disappeared. Furthermore, it intensified the toxic effect of CCl4 on glycogen at 10-100 micrograms/ml. (4) CL1500 (100 micrograms/ml) increased glycogen content of normal cells, but it intensified CCl4-injury effect on glycogen at the same concentration.

[Study on the defluoridation of drinking water with synthetic hydroxyapatite].

Synthetic hydroxyapatite was used as a material for the defluoridation of drinking water. The defluoridation capacity, regeneration the capability of defluoridator and the corresponding parameters of defluoridation and regeneration have been studied with batch and column test. The results showed that the defluoridation capacity of synthetic hydroxyapatite on F- was 3.7-4.3 mg/g in batch test, 5.6 mg/g for break through (1.0 mg/L is considered as the break through point) in column test, and 10.7 mg/g for saturation in column test. The efficiency of regeneration was 46%-64% for saturated hydroxyapatite with surface-coating method.

[Characteristic immunodeficiency syndrome of rapid fatal type of simian immunodeficiency virus infected monkeys].

OBJECTIVE: To observe the characteristic immunodeficiency syndrome of the rapid fatal type of simian immunodeficiency virus (SIV) infected monkeys. METHODS: Eighty rhesus monkeys and 4 cynomolgus monkeys were intravenously inoculated with SIVmac or SIVmac251. The virus isolation and viral titer, estimation by indirect immunofluroresence and viral antibody were determined periodically from monkeys' plasma; lymph node biopsies were performed for pathohistological examination. RESULTS: Twelve out of 84 macaque (14.2%) died of rapid progressive type after inoculation of SIVmac and SIVmac251 in the duration 3 to 4 months. Dying monkeys showed persistent high viremia and low level titre antibody. Eight of 10 pathohistological changes showed severe depletion of lymphoid tissue in spleen and lymph nodes, there were remarkable immunodeficiency with opportunity infection. The other two monkeys appeared moderate lymphoid tissue deletion and hyperplasia without opportunity infections. The survived monkeys' (72/84) lymph nodes biopsies revealed hypoplasia of lymphoid tissue. CONCLUSIONS: The characteristic immunodeficiency syndrome of rapid fatal type of simian immunodeficiency virus infected monkeys could be made with persistent high viremia, low level antibody, severe lymphoid tissue deletion in lymph nodes and spleen, as well as complicated opportunity infections.

Inhibition of transforming growth factor beta-activated kinase 1 confers neuroprotection after traumatic brain injury in rats.

The transforming growth factor beta-activated kinase 1 (TAK1), a member of the Mitogen-activated protein kinase kinase kinase family, is characterized as a key regulator in inflammatory and apoptosis signaling pathways. The aim of the present study was to evaluate the role of the TAK1 pathway in experimental traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were subjected to TBI using a modified Feeney's weight-drop model. The time course showed that a significant increase of TAK1 and p-TAK1 expression in the cortex after TBI. Moreover, TBI induced TAK1 redistribution both in neurons and astrocytes of the lesion boundary zone. The effects of specific inhibition of the TAK1 pathway by 5Z-7-oxozeaenol (OZ, intracerebroventricular injection at 10min post-trauma) on histopathological and behavioral outcomes in rats were assessed at 24h post injury. The number of TUNEL-positive stained cells was diminished and neuronal survival and neurological function were improved with OZ treatment. Biochemically, the high dose of OZ significantly reduced the levels of TAK1 and p-TAK1, further decreased nuclear factor-κB and activator protein 1 activities and the release of inflammatory cytokines. In addition, we found that both 10min and 3h post-trauma OZ therapies could markedly improve neurological function and neuronal survival after long-term survival. These results revealed that the TAK1 pathway is activated after experimental TBI and the inhibitor OZ affords significant neuro- protection and amelioration of neurobehavioral deficits after experimental TBI, suggesting a potential rationale for manipulating this pathway in clinical practice.

Hemoglobin decline in chemotherapy patients prior to and after policy changes affecting use of erythropoiesis-stimulating agents: 2006-2009.

OBJECTIVE: Since 2007, the use of erythropoiesis-stimulating agents (ESAs) to treat anemia in cancer patients receiving chemotherapy has been increasingly restricted in the USA. This study assessed hemoglobin (Hb) decline over time among chemotherapy patients. METHODS: Episodes of chemotherapy care were identified in a large US-oncology electronic medical record database; weekly Hb levels were computed in the first 8 weeks. Unadjusted and adjusted proportions of patient-weeks with Hb decline>1 g/dl (i.e. representing clinically significant decline) within 1 or 2 weeks were analyzed. RESULTS: Between 2006 and 2009, unadjusted proportions of patient-weeks with Hb decline>1 g/dl increased (1-week, from 12.7% to 14.9%; 2-week, from 19.3% to 26.3%). Adjusted 1-week proportions in 2007 were similar to 2006, but increased in 2008 (odds ratio [OR] 1.135; 95% confidence intervals [CI] 1.067, 1.208) and in 2009 (OR 1.235; 95% CI 1.094, 1.395). Adjusted 2-week proportions had the same pattern. CONCLUSIONS: Since restrictions on ESA use were introduced in the USA, more patients have experienced a clinically significant Hb decline after chemotherapy initiation. Initiating anemia therapy at the earliest indicated opportunity may help reduce the risk of such declines.

Effects of different nonionic surfactants on in vitro fermentation characteristics of cereal straws.

The effects of 3 nonionic surfactants (NIS), including alkyl polyglucoside (APG), sorbitan trioleate (Span85), and polyoxyethylene sorbitan monostearate (Tween80), on in vitro fermentation characteristics of maize stover, rice straw, and wheat straw were examined using an in vitro gas production technique. Four levels each of APG, Span85, and Tween80 [0, 0.02, 0.05, and 0.1% (vol/vol) of incubation solution] were tested in a 4 x 4 x 4 factorial arrangement. The NIS generally increased the in vitro maximal gas production (A), but decreased the lag time of cereal straws. The effects of NIS on the rate of gas production (B) were related to the surfactant type and fermented substrate. The NIS generally increased IVDMD and in vitro OM disappearance (IVOMD) of cereal straws, but responses were dose dependent. The NIS increased total VFA concentration of in vitro fermentation supernatant for maize stover and wheat straw, but decreased total VFA concentration for rice straw. The effects of NIS on the molar proportions of acetate, propionate, and butyrate were dependent on the dose and type of NIS and on fermented substrate. Several interactive effects were noted between or among 3 surfactants (APG, Span85, and Tween80) on in vitro gas production variables, IVD-MD, IVOMD, and VFA for each straw; the optimal combinations of 2 or 3 types of NIS were determined according to the responses of IVDMD and IVOMD to NIS addition. The results of this study suggest that NIS may improve in vitro fermentation of low quality roughages and have potential application as feed additives in ruminant production.

Distribution of persistent organic pollutants in soil and grasses around Mt. Qomolangma, China.

Previous literature has reported the fate of persistent organic pollutants (POPs) in mountainous regions, but the Himalayas have received little attention, and few results from this region have been published. The present study collected soil and grass samples from the Mt. Qomolangma (Everest) area, central Himalayas, China, from the elevation range 4700 to 5620 m. We analyzed all samples for organochlorine pesticides (OCPs) to determine the level of OCP contamination in the Qomolangma region. The soil samples contained 0.385 to 6.06 ng g(-1) of DDT only, and these concentrations were lower than those from Europe and mountains close to industrial emissions. Our study detected a number of OCPs in the grass samples, such as hexachlorocyclohexane (HCH) (0.354 to 7.82 ng g(-1)), hexachlorobenzene (HCB) (0.0156 to 1.25 ng g(-1)), endosulfan (0.105 to 3.14 ng g(-1)), and DDT components (1.08 to 6.99 ng g(-1)). Their concentrations were higher than those in pine needles from Alberta, Canada. Our measurements of HCH and DDT in grass samples showed the same or slightly higher concentration levels than reported in moss from Mt. Qomolangma 15 years ago. This result and the analysis of isomer ratios (alpha/gamma-HCH and p-p'-DDE/p-p'-DDT) indicate recent releases of OCPs from a nearby region, possibly from dicofol use in India. We also investigated the elevation distribution of OCPs and found that HCH and HCB were progressively concentrated in colder, higher elevation sites. A bioconcentration factor (BCF) of grass was calculated, and the BCF values increased with the increasing elevation, indicating that the cold condensation of POPs at high-elevation sites may increase the potential threat to vegetation and the food chain in the mountain ecosystem.

Osteoinductivity and biomechanics of a porous ceramic with autogenic periosteum.

Twenty-one dogs were used to study the osteoinductivity and biomechanical properties of a biphasic porous ceramic with autogenic periosteum implanted in muscle. The ceramic implants were swathed in fresh periosteum derived from the same animals and implanted in the femur muscles. The other two groups of animals served as controls using the same material implanted in the femur bones and muscles without periosteum. Biomechanical measurements showed that, in the muscles, the experimental group had a higher bending strength than the unswathed group by the time the samples were harvested. Six months postoperatively, the strength of the samples in the experimental group had almost reached that of normal bones. The results of X-ray diffraction and infrared spectrometric analysis suggested that the degradation rate and speed of tricalcium phosphate (TCP) of the ceramic in the experimental group were faster than in the unswathed samples, but slower than in samples implanted in bones. The bone replacement and bone-inducing activity were excellent in the periosteum-swathed samples. Histologically, satisfactory bone repair was seen in the experimental samples. All results indicate that autogenic periosteum could increase bioactivity of ceramics in heterosites and improve bone formation in the surroundings of porous calcium phosphate ceramics. The data also infer that the complicated procedure of culturing bone growth factors with biomaterials in vitro to obtain bioactive grafts could be replaced by this relatively simple method.