Effect of nicotinic acid supplementation on digestion, metabolism, microbiome, and production in late-lactation Holstein cows.

The purpose of this experiment was to determine if nicotinic acid (NA) effects on dairy cows and rumen microbial characteristics are forage-type dependent (corn silage, CS; grass silage, GS). Four late-lactation (DIM = 225 ± 12 d) Holstein cows were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. The main effects were a CS (66.10% CS) based diet or a GS (79.59%) based diet with or without 12 g/d NA. Each experimental period lasted for 28 d. Milk production and milk components, blood metabolites, apparent total-tract nutrient digestibilities, minutes rumen pH were below 5.8 as an indicator of ruminal acidosis, and body temperature changes were analyzed as indicators of heat stress. Nicotinic acid supplementation did not improve apparent total-tract nutrient digestibility. Feeding a GS-based diet improved NDF and hemicellulose digestibility. Feeding a CS-based diet increased the apparent total-tract digestibility of fat, and minutes rumen pH below 5.8 for a greater proportion of the time. The CS-based diet also improved milk yield, milk fat and protein yields, and ECM yield; however, somatic cell count and BHB were also increased. Supplementing NA tended to decrease nonesterified fatty acids, especially when combined with GS where DMI was low. There was a trend for the total protozoa population to increase when GS and NA were fed but decreased when CS and NA were fed. Nicotinic acid tended to decrease rumen protozoal populations of Dasytricha, but increased populations of Ophryoscolex and Diplodiniinae with GS diets and decreased with CS diets. Entodiniinae were increased with CS but NA had no effect. Body temperature was increased when a CS-based diet was fed when compared with a GS-based diet. More research is needed to determine how NA can affect rumen microbial protein synthesis and what kind of diets will provide the optimum effect.

Stretchable liquid-crystal blue-phase gels.

Liquid-crystalline polymers are materials of considerable scientific interest and technological value. An important subset of these materials exhibit rubber-like elasticity, combining the optical properties of liquid crystals with the mechanical properties of rubber. Moreover, they exhibit behaviour not seen in either type of material independently, and many of their properties depend crucially on the particular mesophase employed. Such stretchable liquid-crystalline polymers have previously been demonstrated in the nematic, chiral-nematic, and smectic mesophases. Here, we report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that remains electro-optically switchable under a moderate applied voltage, and whose optical properties can be manipulated by an applied strain. We also find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and possibilities for low-voltage electro-optic devices.

Rumen fermentation and microbial population in lactating dairy cows receiving diets containing oilseeds rich in C-18 fatty acids.

Sixteen Holstein rumen-cannulated primiparous milking dairy cows were fed a control diet (CN) based on maize silage and soyabean meal during a 4-week period before the start of a 21-d experiment with oilseeds containing high concentration of linoleic acid (Linola™) or linolenic acid (NuLin™). Thereafter, four cows received ad libitum one of each of four dietary treatments comprising of CN, Linola (LN), NuLin (NL) and LN/NL (50/50 % combination). Each LN, NL and LN/NL treatment contained 6 % oil of DM. Rumen digesta samples were collected on days 6, 11, 16 and 21 and milk samples on days 13, 15 and 17. There were no effects (P>0.05) of the oilseeds on pH and concentrations of NH3-N and total volatile fatty acids, while the acetate:propionate ratio was decreased (P< 0.05). The oilseeds also decreased (P< 0.05) protozoa and increased (P< 0.1) total cellulolytic bacteria in rumen fluid, especially when containing high dietary linoleic acid (P< 0.05). The milk protein concentration was increased (P< 0.1) by the dietary linoleic acid, which produced most beneficial results. It was concluded that supplements of linoleic acid in diets of ruminants might contribute to better digestion of dietary fibre and increased quality of milk.

Invited review: Sustainability of the US dairy industry.

The US dairy industry has realized tremendous improvements in efficiencies and milk production since the 1940s. During this time, farm and total cow numbers have decreased and average herd size has increased. This intensification, combined with the shift to a largely urban public, has resulted in increased scrutiny of the dairy industry by social and environmental movements and increased concern regarding the dairy industry's sustainability. In response to these concerns, a group of scientists specializing in animal welfare, nutrient management, greenhouse gas emissions, animal science, agronomy, agricultural engineering, microbiology, and economics undertook a critical review of the US dairy industry. Although the US dairy system was identified as having significant strengths, the consensus was that the current structure of the industry lacks the resilience to adapt to changing social and environmental landscapes. We identified several factors affecting the sustainability of the US dairy industry, including climate change, rapid scientific and technological innovation, globalization, integration of societal values, and multidisciplinary research initiatives. Specific challenges include the westward migration of milk production in the United States (which is at odds with projected reductions in precipitation and associated limitations in water availability for cattle and crops), and the growing divide between industry practices and public perceptions, resulting in less public trust. Addressing these issues will require improved alignment between industry practices and societal values, based upon leadership from within the industry and sustained engagement with other interested participants, including researchers, consumers, and the general public.

Modeling the distribution of ciliate protozoa in the reticulo-rumen using linear programming.

The flow of ciliate protozoa from the reticulo-rumen is significantly less than expected given the total density of rumen protozoa present. To maintain their numbers in the reticulo-rumen, protozoa can be selectively retained through association with feed particles and the rumen wall. Few mathematical models have been designed to model rumen protozoa in both the free-living and attached phases, and the data used in the models were acquired using classical techniques. It has therefore become necessary to provide an updated model that more accurately represents these microorganisms and incorporates the recent literature on distribution, sequestration, and generation times. This paper represents a novel approach to synthesizing experimental data on rumen microorganisms in a quantitative and structured manner. The development of a linear programming model of rumen protozoa in an approximate steady state will be described and applied to data from healthy ruminants consuming commonly fed diets. In the model, protozoa associated with the liquid phase and protozoa attached to particulate matter or sequestered against the rumen wall are distinguished. Growth, passage, death, and transfer of protozoa between both pools are represented. The results from the model application using the contrasting diets of increased forage content versus increased starch content indicate that the majority of rumen protozoa, 63 to 90%, are found in the attached phase, either attached to feed particles or sequestered on the rumen wall. A slightly greater proportion of protozoa are found in the attached phase in animals fed a hay diet compared with a starch diet. This suggests that experimental protocols that only sample protozoa from the rumen fluid could be significantly underestimating the size of the protozoal population of the rumen. Further data are required on the distribution of ciliate protozoa in the rumen of healthy animals to improve model development, but the model described herein does indicate that the attached protozoal population is a significant component of the total rumen protozoal community.

Changes to colour vision on exposure to high altitude.

OBJECTIVES: Several studies have shown deterioration in colour vision at altitudes above 3,000m. These studies have been conducted in photopic (bright daylight) conditions, whereas many military operations take place in mesopic (dim light) conditions. Data suggests that the tritan colour vision axis (blue cones, TA) are more susceptible to hypoxic insult than protan axis (red cones, PA). The objective of this study was to examine colour vision at high altitude, in mesopic conditions, and using a novel method of assessment to discriminate between the tritan and protan axis. METHODS: We examined 42 eyes (21 subjects, mean age 44, range 22-71), at sea level and within 12-36 hours of exposure to 3300m. This was done in a darkened room, with refractive error correction. Colour vision was studied using ChromaTest, a software programme that analyzes colour contrast threshold (CCT) of both TA and PA. We planned to repeat CCT measurement at 4,392m, but technology failure prevented this. Non-parametric paired data was examined using the Wilcoxon signed rank test. RESULTS: There was found to be no change to either the PA (p = 0.409) or the TA (p = 0.871) upon ascent. Within the PA 16 eyes had a lower CCT at high altitude, whilst 26 were higher. In the TA 20 eyes had a lower CCT and 22 were higher. At sea level, mean CCT for PA was 4.21 (SD 2.29) TA was 7.06 (SD 1.77). At 3,300m mean CCT for PA was 4.36 (SD 2.86) and TA was 6.93 (SD 2.39). CONCLUSIONS: This experiment revealed no changes to colour vision with exposure to 3,300m. This may be below the threshold altitude for cone dysfunction, alternatively colour vision deterioration may be less significant in mesopic conditions.

Systemic blood pressure, arterial stiffness and pulse waveform analysis at altitude.

OBJECTIVES: Systemic arterial pressure rises on acute exposure to high altitude and changes in blood pressure (BP) and endothelial function may be important in the pathogenesis of clinical syndromes occurring at high altitude. METHODS: Arterial BP, stiffness (SI) and tone (RI) were studied over 11 days in 17 subjects (three having mild hypertension) ascending to 3,450m and 4,770m using a non-invasive, finger photoplethysmography technique. RESULTS: At 3,450m BP rose from mean 131/75 mmHg (SD 23/12) to 145/86 (23/12) and was maintained at this level (p < 0.001). SI did not change significantly from 8.5 m/sec (2.5) to 9.7 (3.2). RI fell during the first day at 3,450m from 74.4% (7.9) to 70.5% (13.8) (NS p > 0.05) and to 69.9% (12.0) (p < 0.02) at 4,770m but then reverted to baseline. Changes in SI and RI did not relate to changes in blood pressure. Changes in both arterial stiffness and tone were similar in those who developed AMS compared with those who did not. Baseline SI tended to be higher in the three subjects with hypertension 11.1m/sec (SD 2.7)) compared with the normotensives 8.3 m/sec (SD 2.7) (NS) and baseline RI lower 74.7% (7.0) compared with the normotensives 76.5% (8.5) (NS). Changes in SI and RI at altitude in the hypertensive subjects were similar to the non-hypertensive subjects. CONCLUSIONS: We conclude that acute exposure temporarily affected endothelial function as measured by a change in vascular tone but this did not predict the development of AMS. The rise in arterial BP was not related to changes in arterial stiffness or tone.

Supplementation with whole cottonseed causes long-term reduction of methane emissions from lactating dairy cows offered a forage and cereal grain diet.

The objective of our work was to supplement a forage and cereal diet of lactating dairy cows with whole cottonseed (WCS) for 12 wk and to determine whether the expected reduction in CH(4) would persist. A secondary objective was to determine the effect of supplementing the diet with WCS on milk yield and rumen function over the 12-wk feeding period. Fifty lactating cows were randomly allocated to 1 of 2 diets (control or WCS). The 2 separate groups were each offered, on average, 4.2 kg of DM/cow per day of alfalfa hay (a.m.) and 6.6 kg of DM/cow per day of ryegrass silage (p.m.) on the ground in bare paddocks each day for 12 wk. Cows in each group were also individually offered dietary supplements for 12 wk in a feed trough at milking times of 5.4 kg of DM/cow per day of cracked wheat grain and 0.5 kg of DM/cow per day of cottonseed meal (control) or 2.8 kg of DM/cow per day of cracked wheat grain and 2.61 kg of DM/cow per day of WCS. The 2 diets were formulated to be similar in their concentrations of CP and ME, but the WCS diet was designed to have a higher fat concentration. Samples of rumen fluid were collected per fistula from the rumen approximately 4 h after grain feeding in the morning. Samples were taken from 8 cows (4 cows/diet) on 2 consecutive days in wk 2 of the covariate and wk 3, 6, 10, and 12 of treatment and analyzed for volatile fatty acids, ammonia-N, methanogens, and protozoa. The reduction in CH(4) emissions (g/d) because of WCS supplementation increased from 13% in wk 3 to 23% in wk 12 of treatment. Similarly, the reduction in CH(4) emissions (g/kg of DMI) increased from 5.1% in wk 3 to 14.5% in wk 12 of treatment. It was calculated that the average reduction in CH(4) emissions over the 12-wk period was 2.9% less CH(4) per 1% added fat, increasing from 1.5% in wk 3 to 4.4% less CH(4) in wk 12. There was no effect of WCS supplementation on rumen ammonia-N, rumen volatile fatty acids, rumen methanogens, and rumen protozoa. On average over the 12-wk period, supplementation with WCS decreased the yield of milk (10%), fat (11%), protein (14%), lactose (11%), and fat plus protein (12%) and BW gain (31%). The WCS supplementation had no effect on milk fat concentration but resulted in a decrease in concentration of protein (5%) and lactose (11%). The major finding from this study is that addition of WCS to the diet of lactating dairy cows resulted in a persistent reduction in CH(4) emissions (g of CH(4)/kg of DMI) over a 12-wk period and that these reductions in CH(4) are consistent with previous work that has studied the addition of oilseeds to ruminant diets.

Long-term monensin supplementation does not significantly affect the quantity or diversity of methanogens in the rumen of the lactating dairy cow.

A long-term monensin supplementation trial involving lactating dairy cattle was conducted to determine the effect of monensin on the quantity and diversity of rumen methanogens in vivo. Fourteen cows were paired on the basis of days in milk and parity and allocated to one of two treatment groups, receiving (i) a control total mixed ration (TMR) or (ii) a TMR with 24 mg of monensin premix/kg of diet dry matter. Rumen fluid was obtained using an ororuminal probe on day -15 (baseline) and days 20, 90, and 180 following treatment. Throughout the 6-month experiment, the quantity of rumen methanogens was not significantly affected by monensin supplementation, as measured by quantitative real-time PCR. The diversity of the rumen methanogen population was investigated using denaturing gradient gel electrophoresis (DGGE) and 16S rRNA clone gene libraries. DGGE analysis at each sampling point indicated that the molecular diversity of rumen methanogens from monensin-treated cattle was not significantly different from that of rumen methanogens from control cattle. 16S rRNA gene libraries were constructed from samples obtained from the rumen fluids of five cows, with a total of 166 clones examined. Eleven unique 16S rRNA sequences or phylotypes were identified, five of which have not been recognized previously. The majority of clones (98.2%) belonged to the genus Methanobrevibacter, with all libraries containing Methanobrevibacter strains M6 and SM9 and a novel phylotype, UG3322.2. Overall, long-term monensin supplementation was not found to significantly alter the quantity or diversity of methanogens in the rumens of lactating dairy cattle in the present study.

Indole-3-Acetic Acid Biosynthesis in the Mutant Maize orange pericarp, a Tryptophan Auxotroph.

The maize mutant orange pericarp is a tryptophan auxotroph, which results from mutation of two unlinked loci of tryptophan synthase B. This mutant was used to test the hypothesis that tryptophan is the precursor to the plant hormone indole-3-acetic acid (IAA). Total IAA in aseptically grown mutant seedlings was 50 times greater than in normal seedlings. In mutant seedlings grown on media containing stable isotopelabeled precursors, IAA was more enriched than was tryptophan. No incorporation of label into IAA from tryptophan could be detected. These results establish that IAA can be produced de novo without tryptophan as an intermediate.

Protective effect of PCV vaccine against experimental pneumococcal challenge in adults is primarily mediated by controlling colonisation density.

Widespread use of Pneumococcal Conjugate Vaccines (PCV) has reduced vaccine-type nasopharyngeal colonisation and invasive pneumococcal disease. In a double-blind, randomised controlled trial using the Experimental Human Pneumococcal Challenge (EHPC) model, PCV-13 (Prevenar-13) conferred 78% protection against colonisation acquisition and reduced bacterial intensity (AUC) as measured by classical culture. We used a multiplex qPCR assay targeting lytA and pneumococcal serotype 6A/B cpsA genes to re-assess the colonisation status of the same volunteers. Increase in detection of low-density colonisation resulted in reduced PCV efficacy against colonisation acquisition (29%), compared to classical culture (83%). For experimentally colonised volunteers, PCV had a pronounced effect on decreasing colonisation density. These results obtained in adults suggest that the success of PCV vaccination could primarily be mediated by the control of colonisation density. Studies assessing the impact of pneumococcal vaccines should allow for density measurements in their design.

Nonspecific effects of oral vaccination with live-attenuated Salmonella Typhi strain Ty21a.

Epidemiological and immunological evidence suggests that some vaccines can reduce all-cause mortality through nonspecific changes made to innate immune cells. Here, we present the first data to describe the nonspecific immunological impact of oral vaccination with live-attenuated Salmonella Typhi strain Ty21a. We vaccinated healthy adults with Ty21a and assessed aspects of innate and adaptive immunity over the course of 6 months. Changes to monocyte phenotype/function were observed for at least 3 months. Changes to innate and adaptive immune cell cytokine production in response to stimulation with vaccine and unrelated nonvaccine antigens were observed over the 6-month study period. The changes that we have observed could influence susceptibility to infection through altered immune responses mounted to subsequently encountered pathogens. These changes could influence all-cause mortality.

Sub-concussive trauma, acute concussion, and history of multiple concussions: Effects on quiet stance postural control stability.

Although balance control has been studied extensively following acute concussion, little is known regarding repetitive sub-concussive head impacts or chronic exposure to multiple concussive events. Quiet stance postural control was characterized in contact sport athletes at pre-season (n = 135) and post-season (n = 48) to evaluate the effects of subconcussive trauma to the head. To determine the impact of acute concussion on postural control, athletes diagnosed with a concussion during the season (n = 12) were tested at 72-h, 2-weeks, and 1-month post-injury. Because only 4 of the concussed athletes completed baseline testing, control athletes (n = 12) matched for sport, age, body mass index (BMI), and previous concussion history served as a comparison group. Finally, the effects of previous concussion history on quiet stance postural control were determined by comparing pre-season data in contact sport athletes with either zero (Hx0, n = 50) or three or more (Hx3+, n = 25) previous concussions. A force plate was used to compare changes in centre-of-pressure root-mean-square displacement (RMSdisp) and mean-velocity (COPvel) in the anterior/posterior (AP) and medial/lateral (ML) directions. One-minute trials were performed with feet hip-width apart, hands-on-hips, and A) eyes-open and B) eyes-closed. Biomechanical head-impact exposure (impacts over 10 g) was indexed over the season using mastoid-fixed impact sensors. In acutely injured athletes, repeated-measures ANOVA revealed a significant effect of time for RMSdisp AP with increased displacement at 2 weeks compared to 72 h (p = 0.008, 95% CI: -0.180, -0.310 cm). No other COP variables were affected by acute concussion. Moreover, there was no effect of concussion history or repeated sub-concussive impacts on any quiet stance metric. Additionally, head-impact exposure metrics were not correlated with COP metrics. Taken together, the data suggests alterations in COP sway during quiet stance persist in the acute 2-week period after injury. These findings were not present with either a history of multiple concussions or exposure to sub-concussive head impacts indicating acute concussion does not have appear to have long term effects for these measures.

Advances in the available non-biological pharmacotherapy prevention and treatment of acute mountain sickness and high altitude cerebral and pulmonary oedema.

INTRODUCTION: The physiological responses on exposure to high altitude are relatively well known, but new discoveries are still being made, and novel prevention and treatment strategies may arise. Basic information has changed little since our previous review in this journal 10 years ago, but considerable more detail on standard therapies, and promising new approaches are now available. AREAS COVERED: Herein, the authors review the role of pharmacological agents in preventing and treating high-altitude illnesses. The authors have drawn on their own experience and that of international experts in this field. The literature search was concluded in March 2018. EXPERT OPINION: Slow ascent remains the primary prevention strategy, with rapid descent for the management of serious altitude illnesses. Pharmacological agents are particularly helpful when rapid ascent cannot be avoided or when rapid descent is not possible. Acetazolamide remains the drug of choice for prophylaxis of acute mountain sickness. However, evidence indicates that reduced dosage schemes compared to the current recommendations are warranted. Calcium channel blockers and phosphodiesterase inhibitors remain the drugs of choice for the management of high-altitude pulmonary edema. Dexamethasone should be reserved for the treatment of more severe cases of altitude illnesses such as cerebral edema.

Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage.

The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal immunoglobulin G (IgG) to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model, samples were collected from PCV and control-vaccinated adults. In PCV-vaccinated subjects, IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared with pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS-specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity.

F1 rotary motor of ATP synthase is driven by the torsionally-asymmetric drive shaft.

F1F0 ATP synthase (ATPase) either facilitates the synthesis of ATP in a process driven by the proton moving force (pmf), or uses the energy from ATP hydrolysis to pump protons against the concentration gradient across the membrane. ATPase is composed of two rotary motors, F0 and F1, which compete for control of their shared γ -shaft. We present a self-consistent physical model of F1 motor as a simplified two-state Brownian ratchet using the asymmetry of torsional elastic energy of the coiled-coil γ -shaft. This stochastic model unifies the physical concepts of linear and rotary motors, and explains the stepped unidirectional rotary motion. Substituting the model parameters, all independently known from recent experiments, our model quantitatively reproduces the ATPase operation, e.g. the 'no-load' angular velocity is ca. 400 rad/s anticlockwise at 4 mM ATP. Increasing the pmf torque exerted by F0 can slow, stop and overcome the torque generated by F1, switching from ATP hydrolysis to synthesis at a very low value of 'stall torque'. We discuss the motor efficiency, which is very low if calculated from the useful mechanical work it produces - but is quite high when the 'useful outcome' is measured in the number of H(+) pushed against the chemical gradient.

Effect of dietary fiber on the methanogen community in the hindgut of Lantang gilts.

The primary objective of this study was to investigate the effect of dietary fiber on methanogenic diversity and community composition in the hindgut of indigenous Chinese Lantang gilts to explain the unexpected findings reported earlier that Lantang gilts fed low-fiber diet (LFD) produced more methane than those fed high-fiber diet (HFD). In total, 12 Lantang gilts (58.7±0.37 kg) were randomly divided into two dietary groups (six replicates (pigs) per group) and fed either LFD (NDF=201.46 g/kg) or HFD (NDF=329.70 g/kg). Wheat bran was the main source of fiber for the LFD, whereas ground rice hull (mixture of rice hull and rice bran) was used for the HFD. Results showed that the methanogens in the hindgut of Lantang gilts belonged to four known species (Methanobrevibacter ruminantium, Methanobrevibacter wolinii, Methanosphaera stadtmanae and Methanobrevibacter smithii), with about 89% of the methanogens belonging to the genus Methanobrevibacter. The 16S ribosomal RNA (rRNA) gene copies of Methanobrevibacter were more than three times higher (P0.05) was observed in 16S rRNA gene copies of Fibrobacter succinogenes between the two dietary groups, and 18S rRNA gene copies of anaerobic fungi in gilts fed LFD were lower than (P<0.05) those fed HFD. To better explain the effect of different fiber source on the methanogen community, a follow-up in vitro fermentation using a factorial design comprised of two inocula (prepared from hindgut content of gilts fed two diets differing in their dietary fiber)×four substrates (LFD, HFD, wheat bran, ground rice hull) was conducted. Results of the in vitro fermentation confirmed that the predominant methanogens belonged to the genus of Methanobrevibacter, and about 23% methanogens was found to be distantly related (90%) to Thermogymnomonas acidicola. In vitro fermentation also seems to suggest that fiber source did change the methanogens community. Although the density of Methanobrevibacter species was positively correlated with CH4 production in both in vivo (P<0.01, r=0.737) and in vitro trials (P<0.05, r=0.854), which could partly explain the higher methane production from gilts fed LFD compared with those in the HFD group. Further investigation is needed to explain how the rice hull affected the methanogens and inhibited CH4 emission from gilts fed HFD.

Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.

Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.

Luteinizing release hormone tests in impotent diabetic males.

Assessment of pituitary-gonadal function was made in impotent diabetic males using luteinizing hormone-release hormone tests. Serum testosterone, sex-hormone-binding globulin capacity, and basal and incremental gonadotrophin concentrations in the impotent diabetics were similar to those in control diabetics, suggesting a primary neurologic rather than an endocrine defect as the cause of the impotence.