Altered Plasma Fatty Acids Associate with Gut Microbial Composition in Common Variable Immunodeficiency.

PURPOSE: Fatty acid (FA) abnormalities are found in various inflammatory disorders and have been related to disturbed gut microbiota. Patients with common variable immunodeficiency (CVID) have inflammatory complications associated with altered gut microbial composition. We hypothesized that there is an altered FA profile in CVID patients, related to gut microbial dysbiosis. METHODS: Plasma FAs were measured in 39 CVID patients and 30 healthy controls. Gut microbial profile, a food frequency questionnaire, and the effect of the oral antibiotic rifaximin were investigated in CVID patients. RESULTS: The n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) (1.4 [1.0-1.8] vs. 1.9 [1.2-2.5], median (IQR), P < 0.05), and docosahexaenoic acid (DHA) (3.2 [2.4-3.9] vs. 3.5 [2.9-4.3], P < 0.05), all values expressed as weight percent of total plasma FAs, were reduced in CVID compared to controls. Also, n-6 PUFAs (34.3 ± 3.4 vs. 37.1 ± 2.8, mean ± SD, P < 0.001) and linoleic acid (LA) (24.5 ± 3.3 vs. 28.1 ± 2.7, P < 0.0001) and the FA anti-inflammatory index (98.9 [82.1-119.4] vs. 117.0 [88.7-153.1], median (IQR), P < 0.05) were reduced in CVID. The microbial alpha diversity was positively associated with plasma n-6 PUFAs (r = 0.41, P < 0.001) and LA (r = 0.51, P < 0.001), but not n-3 PUFAs (P = 0.78). Moreover, a 2-week course of rifaximin significantly reduced the proportion of n-6 PUFAs (P = 0.04, UNIANOVA). Serum immunoglobulin G (IgG) levels correlated with plasma n-3 PUFAs (rho = 0.36, P = 0.03) and DHA (rho = 0.41, P = 0.009). CONCLUSION: We found a potentially unfavorable FA profile in CVID, related to low IgG levels. High plasma n-6 PUFAs were related to increased gut microbial diversity and altered by rifaximin therapy.

Lower Maternal Chronic Physiological Stress and Better Child Behavior at 18 Months: Follow-Up of a Cluster Randomized Trial of Neonatal Intensive Care Unit Family Integrated Care.

OBJECTIVE: To assess whether Family Integrated Care (FICare) in the neonatal intensive care unit improves maternal chronic physiological stress and child behavior at 18 months of corrected age for infants born preterm. STUDY DESIGN: Follow-up of a multicenter, prospective cluster-randomized controlled trial comparing FICare and standard care of children born at <33 weeks of gestation and parents, stratified by tertiary neonatal intensive care units, across Canada. Primary outcomes at 18 months of corrected age were maternal stress hormones (cortisol, ie, hair cumulative cortisol [HCC], dehydroepiandrosterone [DHEA]) assayed from hair samples. Secondary outcomes included maternal reports of parenting stress, child behaviors (Internalizing, Externalizing, Dysregulation), and observer-rated caregiving behaviors. Outcomes were analyzed using multilevel modeling. RESULTS: We included 126 mother-child dyads from 12 sites (6 FICare sites, n = 83; 6 standard care sites, n = 43). FICare intervention significantly lowered maternal physiological stress as indicated by HCC (B = -0.22 [-0.41, -0.04]) and cortisol/DHEA ratio (B = -0.25 [-0.48, -0.02]), but not DHEA (B = 0.01 [-0.11, 0.14]). Enrollment in FICare led to lower child Internalizing (B = -0.93 [-2.33, 0.02]) and Externalizing behavior T scores (B = -0.91 [-2.25, -0.01]) via improvements to maternal HCC (mediation). FICare buffered the negative effects of high maternal HCC on child Dysregulation T scores (B = -11.40 [-23.01, 0.21]; moderation). For mothers reporting high parenting stress at 18 months, FICare was related to lower Dysregulation T scores via maternal HCC; moderated mediation = -0.17 (-0.41, -0.01). CONCLUSIONS: FICare has long-term beneficial effects for mother and child, attenuating maternal chronic physiological stress, and improving child behavior in toddlerhood. CLINICAL TRIAL REGISTRATION: NCT01852695.

Family Integrated Care for Preterm Infants in China: A Cluster Randomized Controlled Trial.

OBJECTIVE: To explore whether family integrated care (FICare) is feasible and improves the outcomes of preterm infants in China. STUDY DESIGN: This was a multicenter prospective cluster-randomized controlled trial comparing FICare and standard care. The primary outcome was length of stay (LOS). Secondary outcomes were nosocomial infections, duration of supplemental oxygen, breastfeeding, and weight gain. Outcomes were compared using univariate and multivariable analyses adjusted for potential confounders and clustering. RESULTS: We enrolled 601 preterm infants from 11 neonatal intensive care units (FICare, n = 298; control, n = 303). The unadjusted LOS was 30.81 vs 30.26 days (mean ratio, 1.02; 95% CI, 0.85-1.22; P = .85). After adjustment, outcomes in the FICare group were improved compared with the control group, including LOS (28.26 vs 35.04 days; mean ratio, 0.81; 95% CI, 0.72-0.91), total medical expenditures (mean ratio, 0.69; 95% CI, 0.53-0.90), weight gain velocity (15.73 vs 10.30 g/day; mean difference, 5.43; 95% CI, 3.65-7.21), duration of supplemental oxygen (13.11 vs 21.42 days; mean difference, 0.71; 95% CI, 0.50-1.00), nosocomial infection rates (4.13 vs 5.84/1000 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), antibiotic exposure (38.63 vs 57.32/100 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), breastfeeding rates (87.25% vs 55.78%; OR, 5.42; 95% CI, 3.25-9.05), and rehospitalization rates (3.65% vs 7.48%; OR, 0.47; 95% CI, 0.28-0.77). At follow-up to 18 months, breastfeeding rates and weight were significantly (P < .05) higher over time in the FICare group. CONCLUSIONS: FICare was feasible in Chinese neonatal intensive care units and was associated with reduced hospital LOS, medical expenditures, and rates of adverse outcomes.

Evaluating the effect of Family Integrated Care on maternal stress and anxiety in neonatal intensive care units.

Objective: To identify how Family Integrated Care (FICare) affected maternal stress and anxiety. Study Design: This secondary analysis of the FICare cluster randomised controlled trial included infants born between 1 April 2013 and 31 August 2015 at ≤33 weeks' gestation. Mothers completed the PSS:NICU and STAI questionnaires at enrolment and study day 21. Results: 1383 mothers completed the surveys at one or both time-points. The mean PSS:NICU and STAI scores at day 21 were significantly lower in the FICare mothers than controls (PSS:NICU mean [standard deviation] FICare 2.32 [0.75], control 2.48 [0.78], p = 0.0005; STAI FICare 70.8 [20.0], control 74.2 [19.6], p = 0.0004). The sights and sounds, looks and behaviour, and parental role PSS:NICU subscales and the state and trait STAI subscales were all significantly different between FIC are and controls at day 21. The magnitude of change in all stress and anxiety subscales was greater in the FICare group than controls. These differences remained significant after adjustment for confounders with the greatest change in the parental role (least-squares mean [95% confidence interval] FICare -0.65 [-0.72, 0.57], control -0.31 [-0.38, -0.24], p < 0.0001) and state anxiety subscales. Conclusion: FICare is effective at reducing NICU-related maternal stress and anxiety.

A Correlation Analysis between the Nutritional Status and Prognosis of COVID-19 Patients.

PURPOSE: The present study investigated the correlation between the nutritional status and prognosis of COVID-19 patients, and analyzed the epidemiological characteristics of COVID-19 patients with different nutritional status. METHODS: 429 patients who were diagnosed positive for COVID-19 in Hubei Provincial Hospital of Traditional Chinese Medicine from December 2019 to March 2020 were selected and divided into different groups based on Controlling Nutritional Status (CONUT) score (0-4: the low CONUT score group; 5-12: the high CONUT score group). Multivariate logistic regression analysis was applied to investigate the effects of CONUT score on prognosis. RESULTS: The total score of admission status of patients with higher CONUT score was higher than that of those with lower CONUT score (χ2 = 7.152, P = 0.007). The number of adverse outcomes of female was higher than that of male (χ2 = 10.253, P = 0.001). The number of adverse outcomes was higher for patients with smoking history (P = 0.004) or hypertension (χ2 = 11.240, P = 0.001) than those without. Also, the number of adverse outcomes was higher for older patients than younger ones (χ2 = 15.681, P < 0.001). Patients with adverse outcomes had lower urine red blood cell count than patients without adverse outcomes (χ2 = 5.029, P = 0.025). However, BMI, drinking history and diabetes did not show correlation with the prognosis of COVID-19 (P > 0.05).Among patients ≥ 61 years old, the risk of adverse outcomes in the high CONUT score group was 6.191 times that of the low CONUT score group (OR = 6.191, 95% CI: 1.431-26.785).Among the non-diabetic patients, the risk of adverse outcomes in the high CONUT group was 11.678 times that of the low CONUT group (OR = 11.678, 95% CI: 2.754-49.41).For the patients who had a total score of admission status < 6, the risk of adverse outcomes in the high CONUT score group was 8.216 times that of the low CONUT score group (OR = 8.216, 95% CI: 2.439-27.682). CONCLUSION: COVID-19 patients with good nutritional status showed a small chance to have adverse outcomes. Gender, age, hypertension, the number of urine red blood cell count and CONUT score affected the adverse outcomes of patients.

A preliminary study on topical ozonated oil in the therapeutic management of atopic dermatitis in murine.

OBJECTIVE: To explore whether ozonated oil recovery atopic dermatitis (AD) via immunoregulation. METHODS: Mice were repeatedly challenged with the triplex allergens of staphylococcal enterotoxin B, ovalbumin and calcipotriol ointment on the back to develop AD lesions, and were treated with ozonated oil. The lesional skins were scanned by reflectance confocal microscopy to measure the thickness of epidermis. The skin tissues were stained. Th1-type and Th2-type cytokines in serum and in tissues were detected by ELISA and real-time PCR, respectively. RESULTS: Ozonated oil significantly inhibited inflammation and healed the lesions in 7 d. Ozonated oil inhibited NGF expression as compared to the groups treated with vehicle or PBS (p < .01).The serum proteins and lesional transcripts of Th2 cytokines including IL-4 and IL-31 were lower in the ozonated oil treated group than the groups treated with vehicle or PBS (p < .05). The IL-10 level was increased with treatment of ozonated oil (p < .01). On the other hand, the expressions of Th1 cytokines including IL-2, TNF-α, and IFN-γ in the serum were not regulated by ozonated oil. CONCLUSIONS: Our results showed that ozonated oil could suppress inflammation in an AD murine via decreasing Th2-dominant cytokines response and increasing IL-10 expression. These suggest that ozonated oil may be a potential remedy for AD.

Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.f., inhibits prostate cancer bone metastasis.

BACKGROUND: Treatment failure of prostate cancer (PCa) is often due to bone metastasis. Celastrol, an active constituent of Tripterygium wilfordii roots, has shown anti-tumor effects in previous studies in accordance with its indication in traditional Chinese medicine. METHODS: Using a PC-3 cell model, in vitro assays were performed to evaluate the effects of celastrol on proliferation, migration (wound healing assay), tissues invasion (Transwell-Matrigel penetration assay) and vascular endothelial growth factor (VEGF) secretion (enzyme-linked immunosorbent assay). An intra-tibia injection mouse model was used to assess the effect of celastrol on PCa bone metastasis in vivo. RESULTS: Pretreatment with celastrol significantly reduced proliferation of PC-3 cells in a dose-dependent manner and cell migration was much slower than in controls. Significantly fewer cells penetrated the gel-membrane after celastrol administration and their skeletal invasive ability was significantly reduced in a dose-dependent manner. Correspondingly, a significant, dose-dependent decrease in VEGF secretion was observed. In the in vivo mouse model, pretreatment with celastrol (8 µmol l-1) inhibited the tumorigenicity of PC-3 cells so that almost no bone invasion occurred as compared with control injections. Histological examinations using hematoxylin and eosin staining showed that tibiae injected with celastrol pretreated PC-3 cells retained their natural bone structure. CONCLUSIONS: Celastrol may have preventive potential against PCa bone metastasis.

Breaking down barriers: enabling care-by-parent in neonatal intensive care units in China.

BACKGROUND: Denying parents access to their infant in the Neonatal Intensive Care Unit (NICU) is a standard practice in most hospitals across China. Visitation is not usually permitted or may be strictly limited, and NICU care for most neonates is provided by health-care professionals with little participation of the parents. An exception to this rule is the level 2 "Room-In" ward in Qilu Children's Hospital, Shandong University, where parents have 24-hour access to their infants and participate in providing care. METHODS: This retrospective cohort study compared the outcomes of infants who were admitted to the NICU and remained there throughout their stay (NICU-NICU group, n=428), admitted to the NICU and then transferred to the Room-In ward (NICU-RIn group, n=1018), or admitted straight to the Room-In ward (RIn only group, n=629). RESULTS: There were no significant differences in the rates of nosocomial infection, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity between the NICU-NICU and NICU-RIn groups. The rate of necrotizing enterocolitis was significantly lower in the NICU-RIn group (P=0.04), while weight gain and duration of hospital stay were significantly higher (both P<0.001). Rates of adverse outcomes were lower in RIn-only infants due to their low severity of illness on admission. CONCLUSIONS: Allowing parents access to their infant in the NICU is feasible and safe in China, and may result in improvements in infant outcomes. Further studies are required to generate stronger evidence that can inform changes to neonatal care in China.

Wuling Capsule for Major Depressive Disorder: A Meta-analysis of Randomised Controlled Trials.

INTRODUCTION: In China, Wuling capsule, a traditional Chinese medicine consisting of Wuling mycelia of Xylaria nigripes (Kl.) Sacc (a rare type of fungus), is used to treat major depressive disorders. A meta-analysis of randomised controlled trials was performed to compare the efficacy and safety of Wuling capsule alone with Wuling capsule-antidepressant combination in the treatment of major depressive disorders. METHODS: Two assessors independently selected studies, extracted data, and conducted quality assessment and data synthesis. Standard mean difference, risk ratio (RR) ± 95% confidence interval (CI), the number needed to treat, and the number needed to harm were analysed. RESULTS: A total of 12 randomised controlled trials (880 patients; mean age ± standard deviation, 39.7 ± 12.5 years; male patients, 41%) were identified, including 4 trials with Wuling capsule alone (n = 340) and 8 with Wuling capsule-antidepressant (sertraline, mianserin, mirtazapine, and paroxetine) combination (n = 540). The mean length of trial was 5.7 ± 1.3 weeks. Meta-analysis of symptomatic improvement at last-observation endpoint and study-defined response and remission revealed no significant differences between the Wuling capsule alone and antidepressant monotherapy. The Wuling capsule-antidepressant cotreatment was superior to antidepressant monotherapy in symptomatic improvement at last-observation endpoint (standard mean difference: -0.46, p = 0.001) as well as study-defined response (68.4% vs. 56.0%, RR = 1.23; p = 0.03) and remission (46.5% vs. 34.5%, RR = 1.35; p = 0.05). Wuling capsule was associated with fewer adverse drug reactions than antidepressant monotherapy. CONCLUSIONS: Adjunctive Wuling capsule may augment the effects of antidepressants and may be associated with fewer adverse drug reactions. More large-scale and rigorously designed randomised controlled trials with large sample size are warranted to clarify the effectiveness of Wuling capsule for major depressive disorders.

Extract of Ginkgo biloba for Tardive Dyskinesia: Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). We conducted this meta-analysis to systematically examine the efficacy of extract of Ginkgo biloba (EGb), a potent antioxidant possessing free radical-scavenging properties, as a treatment for TD in schizophrenia using randomized controlled trial (RCT) data. METHOD: Drawn from English and Chinese databases, 3 RCTs of EGb augmentation of antipsychotics (APs) vs. AP plus placebo or AP monotherapy were identified. 2 evaluators extracted data. The primary outcome measure was the severity of TD symptoms assessed by the Abnormal Involuntary Movement Scale (AIMS). Weighted mean difference (WMD) and risk ratio (RR) ±95% confidence intervals (CI) were calculated. Statistical analyses were performed using Review Manager (version 5.1.7.0) and STATA (version 12.0). RESULTS: The 3 RCTs (n=299) from China, of 12 weeks duration, involved schizophrenia patients with TD of 55.9±13.4 years old. EGb (240 mg/day) outperformed the control group in reducing the severity of TD and clinical symptoms as measured by the AIMS (trials=3, n=299, WMD: -2.30 (95%CI: - 3.04, -1.55), P<0.00001) and the adverse drug reactions as assessed by the Treatment Emergent Symptom Scale (TESS) (trials=2, n=142, WMD: -2.38 (95%CI: -4.01, -0.74), P=0.004). Both the Positive and Negative Syndrome Scale (PANSS) total score (trials=2, n=239, P=0.87) and all-cause discontinuation (trials=3, n=299, P=0.21) were similar between the EGb and control group. CONCLUSION: This meta-analysis suggests that adjunctive EGb appeared to be an effective and safe option for improving TD in the treatment of schizophrenia patients. However, better RCTs are needed to demonstrate its efficacy and safety especially on cognitive function in TD. PROSPERO: CRD42015024930.

Effect of Acylglycerol Composition and Fatty Acyl Chain Length on Lipid Digestion in pH-Stat Digestion Model and Simulated In Vitro Digestion Model.

In this study, a pH-stat digestion model and a simulated in vitro digestion model were employed to evaluate the digestion degree of lipids depending on different acylglycerols and acyl chain length (that is, diacylglycerol [DAG] compared with soybean oil representing long-chain triacylglycerol compared with medium-chain triacylglycerol [MCT]). In the pH-stat digestion model, differences were observed among the digestion degrees of 3 oils using digestion rate (k), digestion half-time (t1/2 ), and digestion extent (Φmax). The results showed the digestion rate order was MCT > soybean oil > DAG. Accordingly, the order of digestion half-times was MCT < soybean oil < DAG. In simulated in vitro digestion model, digestion rates (k') and digestion half-times (t'1/2 ) were also obtained and the results showed a digestion rate order of MCT (k' = 0.068 min(-1) ) > soybean oil (k' = 0.037 min(-1) ) > DAG (k' = 0.024 min(-1) ). Consequently, the order of digestion half-times was MCT (t'1/2 = 10.20 min) < soybean oil (t'1/2 = 18.74 min) < DAG (t'1/2 = 29.08 min). The parameters obtained using the 2 models showed MCT was digested faster than soybean oil, and that soybean oil was digested faster than DAG.

Relative oxidative stability of diacylglycerol and triacylglycerol oils.

To compare the oxidative stability between diacylglycerol (DAG) oil and conventional triacylglycerol (TAG) oil (that is, soybean oil), the prepared stripped diacylglycerol oil (SDO) and soybean oil (SSBO) were stored at 60 °C in the dark for 144 h. During storage peroxide values (POVs), contents of aldehydes, unsaturated fatty acids were measured to evaluate the oxidative stabilities of the 2 oils. The results showed the content of C18:2, C18:3, and total unsaturated fatty acid decreased faster in DAG oil than in soybean oil, whereas the decreased rate of C18:1 was similar in 2 oils. Also, both rate constants (K1 and K2) obtained from POV (K1 ) and total aldehydes (K2 ) indicated that DAG oil (K1 = 3.22 mmol/mol FA h(-1) , K2 = 0.023 h(-1)) was oxidized more rapidly than soybean oil (K1 = 2.56 mmol/mol FA h(-1) , K2 = 0.021 h(-1)), which was mainly due to the difference of acylglycerol composition of the 2 oils along with higher C18:3 (9.6%) in SDO than SSBO (5.7%). It is concluded that DAG was more easily oxidized than soybean oil at 60 °C in the dark for 144 h.

L-carnitine protects against cyclosporine-induced pancreatic and renal injury in rats.

BACKGROUND: L-carnitine has protective effects against various types of injury. This study was designed to evaluate the beneficial effects of L-carnitine on pancreatic and renal injuries caused by cyclosporine (CsA). METHODS: Rats maintained on a low sodium diet were given vehicle (olive oil, 1 mL/kg/d), CsA (15 mg/kg/d), L-carnitine (50 or 200 mg/kg/d), or a combination of CsA and L-carnitine for 4 weeks. The impact of L-carnitine on pancreatic injury was assessed by blood glucose levels, plasma insulin concentrations, and hemoglobulin A1c (HbA1c). In addition, the protective effects of L-carnitine against CsA-induced kidney injury were evaluated in terms of renal function, histopathology (inflammatory cell influx and tubulointerstitial fibrosis), oxidative stress (8-hydroxy 2'-deoxyguanosine, 8-OHdG), transforming growth factor-betal (TGF-ß1), apoptosis (caspase-3), and autophagy (LC3-II). RESULTS: CsA treatment caused diabetes, renal dysfunction, tubulointerstitial inflammation (ED-1-positive cells), and fibrosis, which were accompanied by an increase in 8-OHdG production and upregulation of TGF-ß1, caspase-3, and LC3-II. Concomitant administration of L-carnitine increased plasma insulin concentrations, decreasing plasma glucose and HbA1c levels. In the kidney, L-carnitine induced dose-dependent improvement of renal function, inflammation, and fibrosis in parallel with suppression of the expression of TGF-ß1 and 8-OHdG. Furthermore, the administration of L-carnitine at a high dose inhibited the expression of caspase-3 and LC3-II. CONCLUSION: These findings suggest that L-carnitine has a protective effect against CsA-induced pancreatic and renal injuries.

Preventive nursing of neonatal clavicular fracture in midwifery: a report of six cases and review of the literature.

PURPOSE: To summarize and analyze the obstetric factors and medical care for neonatal clavicle fracture during delivery. MATERIALS AND METHODS: In 4,456 vaginal deliveries, only six newborns were found with a clavicle fracture in our hospital from October 2002 to October 2011. RESULTS: Clinical findings showed that dystocia and improper midwifery manoeuvres are the two major reasons which lead to newborn clavicular fractures. CONCLUSION: More attention should be paid to non-violent traction and proper treatment of shoulder dystocia.

Different effects of electroacupuncture on esophageal motility and serum hormones in cats with esophagitis.

We aim to investigate the effects of different electroacupuncture (EA) frequencies at ST-36 on esophageal motility, and to compare the effect of EA on serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP). Thirty-two cats were divided into four equal groups. All animals underwent a Heller myotomy. After esophagitis developed two frequencies (2/15 Hz or 2/100 Hz) of EA were delivered into ST-36 (LEA group [low EA], HEA group [high EA]). Animals submitted to EA on a non-point region (EANP) were used as controls (LEANP group, HEANP group), respectively. Esophageal motility was continuously monitored. The lower esophageal sphincter pressure (LESP) decreased significantly after myotomy. The LESP decreased in both LEA and LEANP cats, and in LEA cats the pressure decrease was greater. The LESP increased in the HEA group, which was higher than that in the HEANP group (P < 0.05). High-frequency EA significantly increased the peak amplitude in esophageal peristalsis. There was a decrease in serum GAS and MTL in LEA cats compared with LEANP cats (both P < 0.01). GAS and MTL were higher in the HEA group than in the HEANP group (both P < 0.01). Serum VIP decreased in the HEA group (P < 0.05), while it increased in the LEA group (P < 0.05), compared with EANP groups, respectively. EA with a high frequency at ST-36 enhances LESP as well as esophageal motility, while EA with a low frequency decreases LESP. The effect of EA is acupoint-specific, and this effect appears to be mediated through GAS, MTL and VIP.

Anti-CD45RB monoclonal antibody prolongs renal allograft survival in cynomolgus monkeys.

Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce murine allograft tolerance. The present study was performed to assess the ability of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched kidney transplant model. The recipients were allocated into the following treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1 (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb significantly prolonged renal allograft survival to a median survival of 21 days. Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti-CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with anti-CD45RB mAb resulted in an alteration of the CD45RB(hi) : CD45RB(lo) cell ratio in the peripheral blood. We have, for the first time, demonstrated that an anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti-CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection. These encouraging results indicate that an anti-CD45RB mAb may be valuable in future clinical transplantation.

Spiritual well-being as a dimension of quality of life for patients with advanced cancer and AIDS and their family caregivers: results of a longitudinal study.

Based on a longitudinal, quality-of-life study, this article presents pilot data regarding the spiritual well-being of patients with advanced cancer or AIDS and their family caregivers. Data include similarities and differences between the patient and caregiver populations and patient/family caregiver dyads as well as trends with regard to changes in spiritual well-being during the illness and dying process. The reliability of the Spiritual Well-Being Scale was examined for patient and caregiver groups, as was the relationship between selected demographic variables and spiritual well-being. Implications for practice are discussed.

Cholesterol import by Aspergillus fumigatus and its influence on antifungal potency of sterol biosynthesis inhibitors.

High mortality rates from invasive aspergillosis in immunocompromised patients are prompting research toward improved antifungal therapy and better understanding of fungal physiology. Herein we show that Aspergillus fumigatus, the major pathogen in aspergillosis, imports exogenous cholesterol under aerobic conditions and thus compromises the antifungal potency of sterol biosynthesis inhibitors. Adding serum to RPMI medium led to enhanced growth of A. fumigatus and extensive import of cholesterol, most of which was stored as ester. Growth enhancement and sterol import also occurred when the medium was supplemented with purified cholesterol instead of serum. Cells cultured in RPMI medium with the sterol biosynthesis inhibitors itraconazole or voriconazole showed retarded growth, a dose-dependent decrease in ergosterol levels, and accumulation of aberrant sterol intermediates. Adding serum or cholesterol to the medium partially rescued the cells from the drug-induced growth inhibition. We conclude that cholesterol import attenuates the potency of sterol biosynthesis inhibitors, perhaps in part by providing a substitute for membrane ergosterol. Our findings establish significant differences in sterol homeostasis between filamentous fungi and yeast. These differences indicate the potential value of screening aspergillosis antifungal agents in serum or other cholesterol-containing medium. Our results also suggest an explanation for the antagonism between itraconazole and amphotericin B, the potential use of Aspergillus as a model for sterol trafficking, and new insights for antifungal drug development.

Proteins related to the Nedd4 family of ubiquitin protein ligases interact with the L domain of Rous sarcoma virus and are required for gag budding from cells.

The late assembly (L) domain of retrovirus Gag, required in the final steps of budding for efficient exit from the host cell, is thought to mediate its function through interaction with unknown cellular factors. Here, we report the identification of the Nedd4-like family of E3 ubiquitin protein ligases as proteins that specifically interact with the Rous sarcoma virus (RSV) L domain in vitro and in vivo. We screened a chicken embryo cDNA expression library by using a peptide derived from the RSV p2b sequence, isolating two unique partial cDNA clones. Neither clone interacted with a peptide containing mutations known to disrupt in vivo RSV L domain function or with human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) L domain-derived peptides. The WW domain region of one of the clones, late domain-interacting protein 1 (LDI-1), but not the C2 domain, bound RSV Gag and inhibited RSV Gag budding from human 293 cells in a dominant-negative manner, functionally implicating LDI-1 in RSV particle budding from cells. RSV Gag can be coimmune precipitated from cell extracts with an antisera directed at an exogenously expressed hemagglutinin (HA)-tagged LDI-1 or endogenous Nedd4 proteins. These findings mechanistically link the cellular ubiquitination pathway to retrovirus budding.