Integrase strand transfer inhibitor treatment does not increase the incidence of immune reconstitution inflammatory syndrome in HIV-infected Koreans.

OBJECTIVES: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to determine the incidence and risk factors of IRIS in HIV-infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS. METHODS: This retrospective analysis included adults living with HIV, seen at four university-affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T-cell count < 200 cells/µL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score-matched case-control study between the non-INSTI and INSTI groups was performed. RESULTS: The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB-IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre-ART CD4 T-cell count (< 30 cells/µL), higher pre-ART viral load (≥ 75 000 copies/mL), and TB-OI. CONCLUSIONS: The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.

[Operative strategy and clinical results of complex four part distal radius fractures by combined palmar and dorsal internal fixation].

Objective: To explore a standard procedure for the treatment of combined dorsal and palmar internal fixation for complex four part distal radius fractures and assess its clinical results. Methods: From May 2009 to October 2016, 38 patients(39 sides)who suffered from complex four part distal radius fractures were performed operatively with open reduction and internal fixation via combined dorsal and palmar approach in Department of Orthopaedic Trauma, Qilu Hospital of Shandong University(Qingdao). The series included 22 males(22 sides) and 16 females(17 sides). Age of the patients was 53.5 years ranging from 25 to 79 years.According to Melone classification, there were 34 sides of type of Ⅳ, 5 of type Ⅴ.According to Frykman classification, there were 15 sides of type Ⅶ, 24 sides of type Ⅷ, and all the cases were type C3 according to AO/OTA classification.Preoperatively, the key articular fragments in four part distal radius fractures were identified and the individual fracture patterns from conventional X-ray and CT-scan were analyzed. All the patients were performed combined volar and dorsal fixation.Firstly, a palmar approach which gave access to and fix the palmar-ulnar fragment and the radial styloid fragment was performed.Then a limited dorsal approach across the third extensor compartment which gave access to the dorso-ulnar fragment and a limited dorsal arthrotomy to visualize the radiocarpal joint when necessary were performed.Through dorsal approach, we can address the dorso-ulnar fragment, free intra-articular fragment and direct visualize the joint.Use of a retinacular flap was routinely advocated to help prevent against tendon irritation and rupture.The follow-up control included conventional X-ray, range of motion(ROM), grip strength, and the disabilities of the arm, shoulder and hand index(DASH), as well as the patient-rated wrist evaluation(PRWE) score for functional outcome at 6 and 12 months. Results: Thirty-three patients(34 sides) were followed up for at least 12 months.The would healed well in all cases 2 weeks postoperatively, and no soft tissue infections, necrosis or neurovascular complications occurred.All the fractures of 38 cases(39 sides)healed averaged 3.6 months(ranging from 2.5-5.7 months), and no loss of reduction occurred postoperatively.Anatomic reconstruction with a step or gap of <1 mm was achieved in 37 cases(38 sides), Whereas 5 patients were lost to follow-up at 12 months postoperatively.ROM and grip strength were all recovered to over 85% of the unaffected side(exception of the bilateral patient). Median DASH-index and PRWE were 6.5(0-17) and 9.3(0-20)respectively. Conclusion: Combined volar and dorsal approaches allow achieving anatomic reconstruction in complex four part intra-articular distal radius fractures and reveal good functional outcomes at intermediate follow-up.

Visceral adipose tissue area is associated with coronary stenosis and noncalcified plaques.

OBJECTIVE: Few studies have investigated the relationships between visceral adipose tissue (VAT) and coronary stenosis and noncalcified plaques at the subclinical stage. The aim of this study was to investigate relationship between VAT and coronary lesions assessed by coronary computed tomography (CT) in an apparently healthy population. DESIGN: Retrospective cross-sectional study. SUBJECTS: One thousand six hundred and fifty-eight subjects free of cardiovascular disease underwent coronary CT and abdominal fat CT as part of a routine medical examination. MEASUREMENT: VAT area was measured at the level of the umbilicus using CT. Coronary stenoses and plaques were evaluated using coronary CT. RESULTS: The mean age of the study population was 55.9±8.0 years, and 1198 (72.3%) subjects were men. There were 201 subjects (12.1%) with coronary stenosis <50% and 144 (8.7%) had significant stenosis. Noncalcified plaques were observed in 108 (6.5%) subjects. Coronary stenosis <50% and noncalcified plaques increased steadily as the VAT area increased (P<0.001). The 4th quartile of VAT area was significantly associated with prevalence of coronary stenosis <50% and the presence of noncalcified plaques when compared with the first through third VAT quartiles in the cardiovascular risk factor-adjusted model (odds ratio (OR): 1.58, 95% confidence interval (CI): 1.09-2.30 and OR: 1.66; 95% CI: 1.02-2.68, respectively). CONCLUSION: Excess VAT area was associated with coronary stenosis <50% and noncalcified plaques, independent of traditional cardiovascular risk factors, in an asymptomatic population without a history of coronary artery disease.

Hospital water environment and antibiotic use: key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens.

BACKGROUND: The healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). AIM: To report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). METHODS: The outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case-control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analysed. FINDINGS: The outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics was associated with acquisition of KPC-SM (P < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. CONCLUSION: Our study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant micro-organisms, underscoring the necessity of enhancing infection control practices in these areas.

A redundant epistatic interaction between IRF5 and STAT4 of the type I interferon pathway in susceptibility to lupus and rheumatoid arthritis.

OBJECTIVE: Two transcription factors in the type I interferon pathway, IRF5 and STAT4, have been genetically associated with susceptibility to both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to determine whether these two genes interact with each other to affect the disease susceptibilities. METHODS: The genetic interactions between IRF5 and STAT4 polymorphisms in SLE and RA susceptibility were examined using the epistasis options in PLINK software. This study analyzes the genetic data from 2558 unrelated Korean participants including 589 SLE patients, 987 RA patients, and 982 controls. RESULTS: All 12 polymorphisms were individually associated with SLE susceptibility (p = 2.49 × 10(-8) to 0.00360). Among the three SLE-associated polymorphisms of IRF5, rs77571059, alternatively called CGGGG(3-4) indel, exhibited the lowest p value (4.60 × 10(-5)) and accounted for the observed associations of the other two single-nucleotide polymorphisms (SNPs). Among the nine SLE-associated SNPs of STAT4, rs16833215 exhibited the lowest p value (2.49 × 10(-8)) and accounted for all the other associations. These two polymorphisms, rs77571059 of IRF5 and rs16833215 of STAT4, interacted with each other for SLE susceptibility in a redundant manner (ORinteraction = 0.77, P epistasis = 0.040). Furthermore, these two polymorphisms, which had been individually associated with RA susceptibility, also interacted for RA susceptibility in the same manner (ORinteraction = 0.75, P epistasis = 0.014). CONCLUSIONS: A redundant interaction between IRF5 and STAT4 polymorphisms was found in susceptibility to the type I interferon pathway-associated rheumatic autoimmune diseases, SLE and RA, calling for further studies on confirmation of these findings.

Effects of Polycan, a ß-glucan, on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats.

BACKGROUND AND OBJECTIVE: Polycan is a promising candidate for the treatment of periodontal disease. This study was undertaken to examine whether Polycan, a type of ß-glucan, has a protective effect on ligature-induced experimental periodontitis and related alveolar bone loss in Sprague-Dawley rats. MATERIAL AND METHODS: Polycan was orally administered, daily, for 10 d, at 21.25, 42.5 or 85 mg/kg, beginning 1 d after ligation. Changes in body weight and alveolar bone loss were monitored, and the anti-inflammatory effects of Polycan were determined by measuring the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in gingival tissue. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentrations as a measure of the antioxidant effect. RESULTS: Ligature placement led to a marked decrease in body weight, increased alveolar bone loss and increased concentrations of MPO, IL-1ß, TNF-α and MDA, as well as increased iNOS activity and inflammatory cell infiltration and decreased collagen-fiber content. Histological examination revealed increases in the number and activity of osteoclast cells, decreases in alveolar bone volume and elevated percentages of osteclasts on the alveolar bone surface. Daily oral treatment with 42.5 or 85 mg/kg of Polycan for 10 d led to significant, dose-dependent inhibition of the effect of ligature placement. CONCLUSION: Taken together, these results suggest that 10 d of oral treatment with Polycan effectively inhibits ligature placement-induced periodontitis and related alveolar bone loss via an antioxidant effect.

Impact of inappropriate empiric antimicrobial therapy on outcome in Pseudomonas aeruginosa bacteraemia: a stratified analysis according to sites of infection.

BACKGROUND: The purpose of this study was to evaluate the impact of inappropriate empiric antimicrobial therapy on the outcome of Pseudomonas aeruginosa bacteraemia according to the primary infection site. METHODS: A retrospective cohort study including 202 patients with P. aeruginosa bacteraemia was performed. High-risk sites of infection were defined as the lung, intra-abdominal non-hepatobiliary tract or unknown source. RESULTS: Of the 202 patients with P. aeruginosa bacteraemia, 80 (39.6%) had received inappropriate empiric antimicrobial therapy. No significant difference in the 30-day mortality rate was found between the inappropriate therapy group and the appropriate therapy group (19/80 [23.8%] vs. 32/122 [26.2%], P = 0.692). Patients with pneumonia or non-hepatobiliary tract intra-abdominal infection showed significant association with high mortality, while those with urinary tract or hepatobiliary tract infection showed negative associations with mortality. In the subgroup analysis including 98 patients with high-risk sites of infection, the mortality rate of the inappropriate therapy group was significantly higher than that of the appropriate therapy group (14/26 [53.8%] vs. 23/72 [31.9%], P = 0.035). Inappropriate empiric antimicrobial therapy was also found to be one of the independent risk factors for mortality in patients with high-risk sites of infection (odds ratio [OR] 8.69; 95% confidence interval [CI] 1.86-40.59), along with renal disease, corticosteroid use, polymicrobial infection and higher Pitt bacteraemia score. CONCLUSION: Inappropriate empiric antimicrobial therapy adversely affected the outcome of P. aeruginosa bacteraemia in patients with high-risk sites of infection. Our data suggest that the impact of inappropriate antimicrobial therapy on the outcome of P. aeruginosa bacteraemia may be dependent on the primary site of infection.

Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV.

Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV. CNV was induced in Brown Norway rats using a 532 nm laser. We engineered transferrin, arginine-glycine-aspartic acid (RGD) peptide or dual-functionalized poly-(lactide-co-glycolide) nanoparticles to target delivery of anti-vascular endothelial growth factor (VEGF) intraceptor plasmid to CNV lesions. Anti-VEGF intraceptor is the only intracellularly acting VEGF inhibitory modality. The results of the study show that nanoparticles allow targeted delivery to the neovascular eye but not the control eye on intravenous administration. Functionalizing the nanoparticle surface with transferrin, a linear RGD peptide or both increased the retinal delivery of nanoparticles and subsequently the intraceptor gene expression in retinal vascular endothelial cells, photoreceptor outer segments and retinal pigment epithelial cells when compared to nonfunctionalized nanoparticles. Most significantly, the CNV areas were significantly smaller in rats treated with functionalized nanoparticles as compared to the ones treated with vehicle or nonfunctionalized nanoparticles. Thus, surface-functionalized nanoparticles allow targeted gene delivery to the neovascular eye on intravenous administration and inhibit the progression of laser-induced CNV in a rodent model.

Involvement of transglutaminase in myofibril assembly of chick embryonic myoblasts in culture.

Involvement of transglutaminase in myofibrillogenesis of chick embryonic myoblasts has been investigated in vitro. Both the activity and protein level of transglutaminase initially decreased to a minimal level at the time of burst of myoblast fusion but gradually increased thereafter. The localization of transglutaminase underwent a dramatic change from the whole cytoplasm in a diffuse pattern to the cross-striated sarcomeric A band, being strictly colocalized with the myosin thick filaments. For a brief period prior to the appearance of cross-striation, transglutaminase was localized in nonstriated filamental structures that coincided with the stress fiber-like structures. When 12-o-tetradecanoyl phorbol acetate was added to muscle cell cultures to induce the sequential disassembly of thin and thick filaments, transglutaminase was strictly colocalized with the myosin thick filaments even in the myosacs, of which most of the thin filaments were disrupted. Moreover, monodansylcadaverine, a competitive inhibitor of transglutaminase, reversibly inhibited the myofibril maturation. In addition, myosin heavy chain behaved as one of the potential intracellular substrates for transglutaminase. The cross-linked myosin complex constituted approximately 5% of the total Triton X-100-insoluble pool of myosin molecules in developing muscle cells, and its level was reduced to below 1% upon treatment with monodansylcadaverine. These results suggest that transglutaminase plays a crucial role in myofibrillogenesis of developing chick skeletal muscle.

Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions.

Caspase-11, a member of the murine caspase family, has been shown to be an upstream activator of caspase-1 in regulating cytokine maturation. We demonstrate here that in addition to its defect in cytokine maturation, caspase-11-deficient mice have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion (MCAO), a mouse model of stroke. Recombinant procaspase-11 can autoprocess itself in vitro. Purified active recombinant caspase-11 cleaves and activates procaspase-3 very efficiently. Using a positional scanning combinatorial library method, we found that the optimal cleavage site of caspase-11 was (I/L/V/P)EHD, similar to that of upstream caspases such as caspase-8 and -9. Our results suggest that caspase-11 is a critical initiator caspase responsible for the activation of caspase-3, as well as caspase-1 under certain pathological conditions.

Association between central venous pressure and blood loss during hepatic resection in 984 living donors.

BACKGROUND: Although low central venous pressure (CVP) anesthesia has been used to minimize blood loss during hepatectomy, the efficacy of this technique remains controversial. We therefore assessed the association between blood loss and CVP during hepatic resection, and examined significant determinants associated with intraoperative hemorrhage during hepatectomy in living donors. METHODS: Between April 2004 and April 2008, 984 living donors who underwent a hepatic resection were assessed retrospectively. Univariate and multivariate analyses were performed to explore the relationships between intraoperative blood loss and several variables including CVP. RESULTS: The mean intraoperative blood loss was 691.3 +/- 365.5 ml. Only four donors required packed red blood cell transfusions (mean, 1.5 U). The mean duration of hepatic resection was 92.1 +/- 26.3 min. The mean, maximum, and minimum values of CVP measured during hepatectomy were 4.6 +/- 1.7, 5.3 +/- 1.8, and 4.0 +/- 1.8 mmHg, respectively, and were not significantly correlated with intraoperative blood loss. On multivariate analysis, predictors of hemorrhage were liver fatty change, gender, and body weight, but none of the mean CVP, surgeons, anesthesiologists, anesthesia duration, resected liver volume, hepatectomy type, systolic blood pressure, heart rate, or body temperature were significant. CONCLUSIONS: CVP during hepatic resection was not associated with intraoperative blood loss in living liver donors, suggesting that CVP may not be an important factor in predicting blood loss during hepatectomy in healthy subjects.

Changes of immunophysiological characteristics in neonatal calves experimentally challenged with mixture of live bacteria and virus.

The aim of the present study was to define efficient immunophysiological parameters in neonatal Holstein calves with an experimentally induced microbial infection. Calves (n = 15) were challenged with classical swine fever virus (LOM strain) and Erysipelothrix insidiosa live vaccine by intravenous injection at 3 wk of age except for control calves (n = 4). The level of total serum IgA was significantly increased at 14 and 19 d post-experimental challenge (DPEC) compared with that in calves at -2 DPEC. At 5 DPEC, relative amounts of bacterial- and viral-specific IgA increased significantly and were sustained until 26 DPEC. In the hematology assay, the neutrophil:lymphocyte ratio (%) in whole blood was significantly decreased at 14 DPEC because of a significant increase in lymphocytes and a coincident decrease in neutrophils. The percentages of CD4+ and CD25+ T cells were significantly decreased at 14 DPEC and returned to initial levels at 19 DPEC. It is intriguing to note that the level of serum lactoferrin was significantly decreased by the microbial challenge within 1 d. The concentration of haptoglobin was increased within 3 d and gradually decreased in calves after microbial challenge. Our results suggest that 1) bovine serum lactoferrin plays an important role in the innate immune response against microbial infection at an early stage and 2) experimentally induced microbial challenge using porcine live bacterial and viral vaccine in calves could be a good experimental model to evaluate the effect of diet or stress induced by environmental change on the immune responses against microbial infection.

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study.

OBJECTIVES: To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. METHODS: We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. RESULTS: Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05). CONCLUSIONS: Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.

Slow vertical saccades in the frontotemporal dementia with motor neuron disease.

BACKGROUND: Ocular motor abnormalities play an important role in differential diagnoses of Pick complex diseases. OBJECTIVES: We evaluated how frequently supranuclear vertical saccadic impairment was observed in patients with frontotemporal dementia with motor neuron disease (FTD-MND). In addition, we tried to characterize their vertical saccadic abnormalities. MATERIALS AND METHODS: Eleven patients with FTD-MND were recruited. Supranuclear vertical saccadic impairment on gross examination was defined as slow saccades with or without reduction in the final amplitude of the movement accompanied by intact oculocephalic reflex. We also recorded their saccades in 6 out of 11 patients using 2-dimensional videooculography (VOG). We measured the amplitude and peak velocity of each saccade. RESULTS: On bedside examination, supranuclear vertical saccadic impairment was observed in 9 of 11 patients. One of the two remaining patients could not be evaluated due to poor cooperation and the other showed normal saccades. Five of nine patients with ocular abnormalities and one patient with normal saccade on gross examination underwent the VOG studies. The results showed that all the five patients with gross ocular abnormalities, compared with age-matched controls, had slowing of vertical saccades. Three out of five patients also showed slowing even in the large horizontal saccades. CONCLUSIONS: Our results showed that slow vertical saccades are common in FTDMND. FTD-MND could be another disease that affects vertical gaze among Pick complex disease. Future pathologic studies are needed to confirm the involvement of the burst neurons in the dorsal midbrain in patients with FTDMND.

Concordance of results of blood and tissue cultures from patients with pyogenic spondylitis: a retrospective cohort study.

OBJECTIVES: To investigate the concordance of results of blood and tissue cultures in patients with pyogenic spondylitis. METHODS: We searched for patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures by retrospective review of medical records in three tertiary university-affiliated hospitals between January 2005 and December 2015. The species and antimicrobial susceptibility patterns of isolates from blood and tissue cultures were compared. RESULTS: Among 141 patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures, the species of blood and tissue isolates were identical in 135 patients (95.7%, 135/141). Excluding the four anaerobic isolates, we investigated antimicrobial susceptibility patterns of 131 isolates of the same species from blood and tissue cultures. Antibiotic susceptibility patterns were identical in 128 patients (97.7%, 128/131). The most common isolates were Staphylococcus aureus (86 patients; 85 concordant and one discordant), followed by streptococcus (24 patients; 22 concordant and two discordant), and Escherichia coli (eight patients; all concordant). CONCLUSIONS: We suggest that a positive blood culture from patients with pyogenic spondylitis could preclude the need for additional tissue cultures, especially when S. aureus and streptococcus grew in blood cultures.

Sensory quality characteristics with different beef quality grades and surface texture features assessed by dented area and firmness, and the relation to muscle fiber and bundle characteristics.

The main objective of this study was to compare the eating quality among the groups categorized by the Korean beef quality grade and texture feature of exposed muscle surface assessed by extent of dented areas and firmness. Additionally, this study also investigated the effects of fiber and bundle characteristics on texture feature to establish the cause of differences in muscle surface texture. Significant differences were observed in the sensory quality characteristics among the quality grades mainly determined by marbling score (P < 0.05). However, the coarse texture group with a dented surface required a higher initial force to penetrate meat (P < 0.001), was more difficult to break meat into fragments (P < 0.001), and had a higher amount of perceptible residue in the mouth (P < 0.01) compared to the fine texture group. These differences in the surface texture features between the fine and coarse groups could be explained by bundle area and fiber number per each bundle.

Structural growth, rumen development, and metabolic and immune responses of Holstein male calves fed milk through step-down and conventional methods.

Structural growth, feed consumption, rumen development, metabolic response, and immune response were studied in Holstein calves fed milk through either a conventional method or a step-down (STEP) method. In the conventional method, calves (n = 20) were fed colostrum and then milk at a rate of 10% of their BW for the entire period of 44 d. In the STEP method, calves (n = 20) were given colostrum and then milk at a rate of 20% of their BW for 23 d, which was reduced (between d 24 to 28) to 10% of their BW for the remaining 16 d. The calves on both methods were weaned gradually by diluting milk with water between d 45 and 49. After weaning, feed consumption, structural growth, and body weight gain were monitored until calves were 63 d of age. At d 63, twelve calves (6/treatment) were euthanized and rumen papillae length, papillae width, rumen wall thickness, and emptied forestomach weight were recorded. At wk 4, 7, and 9, ruminal contents were collected to enumerate rumen metabolites. The STEP-fed calves consumed a greater amount of milk than conventionally fed calves during the pre-STEP (d 1 to 28), post-STEP (d 29 to 49), and preweaning (d 1 to 49) periods. Consumption of starter and hay was greater during the pre-STEP period and lesser during the post-STEP and postweaning (d 50 to 63) periods in calves on the conventional method than on the STEP method. Body weight gain and structural growth measurements of calves were greater on the STEP method than on the conventional method. A hypophagic condition caused by greater milk consumption depressed solid feed intake of STEP-fed calves during the pre-STEP period, and a hyperphagic response caused by a reduced nutrient supply from milk triggered their consumption of solid feed during the post-STEP and postweaning periods. Ruminal pH and concentrations of ammonia, total volatile fatty acids, acetate, propionate, butyrate, and plasma beta-hydroxybutyrate were higher in calves on the STEP method and at weaning and postweaning (d 63) were lower in calves on the conventional method. Emptied weight of the forestomach, rumen wall thickness, papillae length, papillae width, and papillae concentration were higher in calves on the STEP method than in those on the conventional method. Blood glucose was lower, and blood urea nitrogen and beta-hydroxybutyrate at weaning and postweaning were higher in STEP-fed calves. Serum IgG, IgA, and triglycerides for 1, 2, and 3 wk of age were higher in calves on the STEP method than in those on the conventional method. In conclusion, greater feed consumption, BW gain, and structural growth, and a more metabolically and physically developed rumen were observed in calves on the STEP method than in those on the conventional method.

Antibacterial activities of some mosses including Hylocomium splendens from South Western British Columbia.

The antibacterial activity of methanol extracts of ten moss species and fractions prepared from 80% methanol extract of Hylocomium splendens were evaluated by disk diffusion method. Nine moss species showed antibacterial activity against Gram (+) bacteria, in particular H. splendens and its ethyl acetate fractions showed stronger activity. Enhancement of antibacterial activity against Staphylococci by UV-A light irradiation was demonstrated in the extracts of Bartramia pomiformis, Ceratodon purpureus and Neckera douglasii.

Onion (Allium cepa L.) peel extract (OPE) regulates human sperm motility via protein kinase C-mediated activation of the human voltage-gated proton channel.

Onion (Allium cepa L.) and quercetin protect against oxidative damage and have positive effects on multiple functional parameters of spermatozoa, including viability and motility. However, the associated underlying mechanisms of action have not yet been identified. The aim of this study was to investigate the effect of onion peel extract (OPE) on voltage-gated proton (Hv1) channels, which play a critical role in rapid proton extrusion. This process underlies a wide range of physiological processes, particularly male fertility. The whole-cell patch-clamp technique was used to record the changes in Hv1 currents in HEK293 cells transiently transfected with human Hv1 (HVCN1). The effects of OPE on human sperm motility were also analyzed. OPE significantly activated the outward-rectifying proton currents in a concentration-dependent manner, with an EC50 value of 30 µg/mL. This effect was largely reversible upon washout. Moreover, OPE induced an increase in the proton current amplitude and decreased the time constant of activation at 0 mV from 4.9 ± 1.7 to 0.6 ± 0.1 sec (n = 6). In the presence of OPE, the half-activation voltage (V1/2 ) shifted in the negative direction, from 20.1 ± 5.8 to 5.2 ± 8.7 mV (n = 6), but the slope was not significantly altered. The OPE-induced current was profoundly inhibited by 10 µm Zn2+ , the most potent Hv1 channel inhibitor, and was also inhibited by treatment with GF109203X, a specific protein kinase C (PKC) inhibitor. Furthermore, sperm motility was significantly increased in the OPE-treated groups. OPE exhibits protective effects on sperm motility, at least partially via regulation of the proton channel. Moreover, similar effects were exerted by quercetin, the major flavonoid in OPE. These results suggest OPE, which is rich in the potent Hv1 channel activator quercetin, as a possible new candidate treatment for human infertility.