Comparative efficacy of antimicrobial treatments in dairy cows at dry-off to prevent new intramammary infections during the dry period or clinical mastitis during early lactation: a systematic review and network meta-analysis.

A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23-0.65; cloxacillin, RR = 0.55, 95% CI 0.38-0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26-0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.

Comparative efficacy of teat sealants given prepartum for prevention of intramammary infections and clinical mastitis: a systematic review and network meta-analysis.

A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25-0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.

An investigation into possible quantum chaos in the H2 molecule under intense laser fields via Ehrenfest phase space (EPS) trajectories.

By employing the Ehrenfest "phase space" trajectory method for studying quantum chaos, developed in our laboratory, the present study reveals that the H2 molecule under intense laser fields of three different intensities, I = 1 × 1014 W/cm2, 5 × 1014 W/cm2, and 1 × 1015 W/cm2, does not show quantum chaos. A similar conclusion is also reached through the Loschmidt echo (also called quantum fidelity) calculations reported here for the first time for a real molecule under intense laser fields. Thus, a long-standing conjecture about the possible existence of quantum chaos in atoms and molecules under intense laser fields has finally been tested and not found to be valid in the present case.

Synthesis and characterization of AgI-Ag2O-SeO2 glass-nanocomposites embedded with beta-AgI and Ag2SeO3 nanocrystals.

Glass-nanocomposites of compositions xAgI - (1 - x)(0.40Ag2O-0.60SeO2) for 0.15 < or = x < or = 0.30 were prepared by quenching the melt of the appropriate mixtures of the chemicals AgI, AgNO3 and SeO2. Differential scanning calorimetry (DSC) was employed to determine the glass transition and crystallization temperatures. The as-prepared samples were heat-treated above glass transition temperature to observe the growth of nanoparticles. X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) were used to explore the microstructure of these samples. These studies revealed the presence of beta-AgI and Ag2SeO3 nanocrystals in both the as-prepared and heat-treated samples. The particle size was found to decrease with the increase of AgI content in both cases. The heat-treated samples showed increased tendency of crystallization for the compositions with higher AgI content. The beta-alpha phase transition of AgI crystals was observed at approximately 147-149 degrees C for heat-treated samples. Fourier transform infrared (FTIR) spectra revealed that the basic structure of the glassy network remained invariant to change of AgI content as well as to heat-treatment.

Functionalizing titania nanoparticle surfaces in a fluidized bed plasma reactor.

Functionalizing nanoparticle surfaces is essential for achieving homogeneous dispersions of monodisperse particles in polymer nanocomposites for successful utilization in engineering applications. Functionalization reduces the surface energy of the nanoparticles, thereby limiting the tendency to agglomerate. Moreover, reactive groups on the surface can also participate in the polymerization, creating covalent bonds between the inorganic and organic phases. In this paper, a fluidized bed inductively coupled plasma (FB-ICP) reactor is used to break apart the agglomerates and functionalize commercial TiO2 nanoparticle powders in a batch of several grams. The fluidized bed could be implemented into a continuous flow reactor, potentially making this a viable method to treat larger quantities of commercial powders. The particles are treated with acrylic acid (AA) and tetraethylorthosilicate (TEOS) plasma and the functionalized particles were collected separately from bulk powder. High resolution transmission electron microscopy (HRTEM) analysis showed that the particles were coated uniformly with polymer coatings with thicknesses around a few nanometers. Fourier-transformed infrared spectroscopy (FTIR) studies of the polymer-coated particles showed the presence of different functional groups (poly-acrylic acid/siloxane) similar to that present in the bulk films. The dispersion behavior of the TiO2 nanoparticles showed much improvement with reduced agglomerate size.

Manipulating higher partial-wave atom-atom interactions by strong photoassociative coupling.

We show that it is possible to change not only s-wave but also higher partial-wave atom-atom interactions in a cold collision in the presence of relatively intense laser fields tuned near a photoassociative transition.

Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit.

Combination therapy with an intravenous inovasodilator and inhaled nitric oxide (NO) may be appropriate in patients with pulmonary hypertension and associated right ventricular failure. We examined whether dobutamine and inhaled NO would have additive pulmonary vasodilator effects in experimental pulmonary hypertension. Pulmonary hypertension was produced in anesthetized, mechanically ventilated rabbits by infusion of U46619, a thromboxane analogue. Dobutamine was administered in increasing doses (2.5-20 microg/kg/min) with and without inhaled NO (40 ppm). Dobutamine produced dose-dependent decreases in pulmonary vascular resistance (PVR) and mean arterial pressure (MAP) and increases in cardiac output (CO). Inhaled NO alone decreased pulmonary artery pressure (PAP) and PVR with no effect on MAP or CO. The effects of dobutamine and inhaled NO were additive, so that at each dose of dobutamine, inhaled NO decreased PAP and PVR with no effect on systemic hemodynamics. This study suggests that the combination of dobutamine and inhaled NO should produce additive pulmonary vasodilation in patients with pulmonary hypertension and associated right ventricular dysfunction.

Additive effects of inhaled nitric oxide and intravenous milrinone in experimental pulmonary hypertension.

OBJECTIVE: To determine whether inhaled nitric oxide (IN0) and intravenous milrinone have additive pulmonary vasodilator effects in a rat model of pulmonary hypertension. DESIGN: Prospective, experimental study. SETTING: Animal laboratory of a university medical center. SUBJECTS: Male New Zealand White rabbits. INTERVENTIONS: Anesthetized rabbits were mechanically ventilated and instrumented for measurement of systemic mean arterial pressure (MAP), pulmonary artery pressure (PAP), left atrial pressure, and cardiac output (CO). After baseline measurements, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg iv) was administered. Pulmonary hypertension was produced by the continuous infusion of U46619, a thromboxane A2 mimetic. INO (40 ppm) was added to the inspired gas, and hemodynamic measurements were obtained before and after INO. Milrinone was administered sequentially as a 30-mg/kg bolus followed by a 3-microg/kg/min infusion, a 100-mg/kg bolus followed by a 10-microg/kg/min infusion, and a 300-mg/kg bolus followed by a 30-microg/kg/min infusion (M3). Hemodynamic measurements were obtained with and without INO at each dose of milrinone. MEASUREMENTS AND MAIN RESULTS: During U46619-induced pulmonary hypertension, INO decreased PAP and pulmonary vascular resistance (PVR) but did not affect MAP, systemic vascular resistance (SVR), or CO. Milrinone dose dependently decreased PAP, PVR, MAP, and SVR and increased CO. At each dose of milrinone, INO further decreased PVR but not SVR. M3 decreased PVR 49%, and the addition of INO decreased PVR an additional 19% so that PAP and PVR decreased to baseline values. CONCLUSIONS: Milrinone and INO both decrease pulmonary hypertension individually, and the combination produces additive effects. Combination therapy may produce potent and selective pulmonary vasodilation during the treatment of pulmonary hypertension.

Inhaled nitric oxide potentiates actions of adenosine but not of sodium nitroprusside in experimental pulmonary hypertension.

Inhaled nitric oxide (NO), a selective pulmonary vasodilator, increases intracellular cyclic guanosine monophosphate. In contrast, adenosine, another selective pulmonary vasodilator, increases intracellular cyclic adenosine monophosphate. There has been only limited study on effects of inhaled NO combined with other pulmonary vasodilators. The current study examined the hypothesis that inhaled NO would potentiate in vivo pulmonary vasodilator effects of adenosine, but not those of sodium nitroprusside (SNP). Like inhaled NO, SNP acts via cyclic guanosine monophosphate. Rabbits were anesthetized and mechanically ventilated. The NO synthesis inhibitor NG-nitro-L-arginine methyl ester was administered. U46619, a thromboxane A2 mimetic, was infused to produce pulmonary hypertension. Rabbits then received either SNP at doses of 0.5, 1, 2, 4, 8, 16, and 32 microg/kg/min or adenosine at doses of 12.5, 25, 50, 100, 150, and 300 microg/kg/min. Hemodynamic measurements were obtained with or without inhaled NO (40 ppm) at each dose of SNP or adenosine. During U46619-induced pulmonary hypertension, inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance. Adenosine and SNP produced dose-related decreases in pulmonary artery pressure and pulmonary vascular resistance and increases in cardiac output. Inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance at all doses of adenosine, but had no significant pulmonary vasodilator effects at doses of SNP >0.5 microg/kg/min. We conclude that inhaled NO does not produce additional pulmonary vasodilation over that achieved at higher doses of SNP, but does produce additional vasodilation when combined with a vasodilator having different mechanisms of action. Since both inhaled NO and adenosine produce selective pulmonary vasodilation, such combination therapy may be effective in patients with pulmonary hypertension.

Reaching out beyond the hills: HIV prevention among injecting drug users in Manipur, India.

Outreach interventions using ex-IDUs to inform and educate their peers about HIV/AIDS prevention measures have been found to be effective in the United States and other developed countries. While HIV/AIDS prevention programmes targeting IDUs have also been implemented in a number of developing countries, very little information is available on the process of implementation of these programmes. This paper attempts to document some of this knowledge by describing the implementation process of an outreach intervention targeting IDUs in a small town--Churachandpur--with high injection drug use and high HIV infection rates, in the north-eastern state of Manipur. The paper describes the barriers encountered in implementing the outreach and how these barriers were minimized. In conclusion, the paper makes the case for targeting outreach to the larger community before targeting the IDUs.

PIP: In the small town of Churanchandpur, Manipur, India, heroin injection began in the early 1980s. Over 80% of the injecting drug users (IDUs) in the state of Manipur are estimated to be HIV-positive. The implementation of an outreach intervention targeting IDUs is detailed. An advisory committee sought to create a supporting environment for the outreach by minimizing police harassment of IDUs. Church leaders were also provided information about the HIV/AIDS problem as were families of IDUs and the community. Outreach workers were recruited from the community and trained regarding HIV/AIDS epidemiology, prevention, antibody testing, and referral. The IDUs were approached in pairs by the outreach workers who delivered prevention messages: not to use drugs and injecting equipment; cleaning syringes with bleach; avoiding multiple sex partners; and using condoms. Within 1 year, 750 of the estimated 800 IDUs were reached and 3930 bleach kits and 4734 condoms were distributed. Referrals were made for medical problems (thrombophlebitis, abscess, and infections) to a team doctor or drop-in centers. Later, active IDUs were also recruited to help reach new IDUs. Dealers' homes were also visited to distribute risk reduction information and bleach kits. At the six drug treatment centers regular weekly visits were paid to provide prevention information. Weekly visits were made to the jail with a similar bid. A drug users' organization was formed which discussed health concerns faced by IDUs on a weekly basis. Two drop-in centers were also set up, where an average of 10-15 IDUs could come daily and discuss any problem with the field staff. Constraints on the outreach implementation included illegal drug use, low morale among the outreach workers, lack of understanding of the community and church, the cumbersome bureaucracy, the deteriorating political situation, no facilities for voluntary HIV testing and counseling, and the relapse of outreach workers into drug use.

Injection drug use in Calcutta: a potential focus for an explosive HIV epidemic.

Our objective was to assess HIV risk perceptions, risk behaviours and factors that may facilitate an increase in injection drug use in Calcutta. Focus group discussions and in-depth interviews were conducted with a selected group of drug users to delineate drug use patterns, languages used to express addictive and related experiences and acceptance of harm minimization messages. Results from these were used to develop a semi-structured interview instrument which was used to interview 111 drug users (76 IDUs and 35 non-IDUs) recruited from jails and detoxification centres. Secondary data of narcotic seizures for the last 5 years were collected from the Calcutta police department. Data on percentage of IDUs admitted to large detox facility in the city was also collected. Findings show that HIV/AIDS knowledge and risk perceptions were low; sharing of injection equipment was reported by 66% of the injectors; and condom use was insignificant. Non-availability, rising cost and increasing tolerance to heroin were cited as factors contributing to switch to injection. Ecological association was found between intensified police activity and an increase in: the amount of smokable heroin seized; increased injection of buprenorphine; and admission to detoxification centres. In addition to HIV, IDUs were also found to be prone to hepatitis B and C. The findings suggest an urgent need for developing and implementing community-based HIV prevention interventions targeting drug users in Calcutta.

Mechanical ventilation and adjuncts in acute respiratory distress syndrome.

Acute respiratory distress syndrome is a response of the lung to both direct and indirect insults. Although much knowledge has been gained in understanding the pathophysiology of the syndrome, overall mortality in the past 25 years remains unchanged. Application of scientific knowledge to present-day technology has yielded advances in ventilator and pharmacological support for the patient with ARDS. Emphasis is now made on the prevention of iatrogenic lung injury with the use of pressure-limited mechanical ventilation, permissive hypercapnia, and artificial means of gas exchange (discussed in the chapter by Dr Furukawa). The role of INO and surfactant, as well as antimediator therapy, in the armamentarium against ARDS appears promising but awaits definitive clinical trials. Only with progress and newer therapies will we be able to improve the outlook for patients and families in the future.

A cross-sectional study on factors including HIV testing and counselling determining unsafe injecting practices among injecting drug users of Manipur.

In India, a steep increase in the prevalence of HIV (0% to 50% within six months) among the IDUs has been reported in Manipur, a north eastern state in 1990. In spite of large scale intervention program like educational campaign and widespread voluntary HIV testing in this state, the infection has quickly spread to the heterosexual population at large. The determinants of risk taking behaviors like sharing of unclean needle among the IDU population has been explored in this paper. A cross sectional study has been carried out among all of the 488 IDUs who attended any detoxification centers and prison during last two years at Imphal, the capital city of this state. Self reported behaviors based on the pre-scheduled interview were recorded and participation rate was satisfactory. The data was compared to a similar survey carried out by us in 1990. Although there has been decline in risk behavior among the IDUs, a logistic regression analysis reveals that unsafe needle sharing behavior is not influenced by the knowledge on HIV transmission, educational status or history of HIV testing or serostatus of the individual. The limitation of cross sectional nature of the study, bias due to collection of data in prison, self reported behavior, possible differences with street samples of the addict are discussed.

PIP: During August 1991 to July 1993, in Manipur State, India, social workers interviewed 488 intravenous drug users (IDUs) who were drug-free for at least 7 days and who had been institutionalized within the previous 6 months in 1 of 9 detoxification centers (the largest being the Manipur Central Jail) in Imphal city. They aimed to examine the extent of risky injecting behavior, determinants of safer injecting behavior, and any change in risky behavior since 1990. The research team provided HIV counseling after the interview. This counseling was in addition to routine counseling provided by the centers. Almost all (99%) subjects were male. The median age was 26 years. IDUs in this study were less likely to currently share needles than in 1990 (70% vs. 96%; p 0.01). IDUs in 1993 were less likely to report never cleaning needles than in 1990 (10% vs. 62%; p 0.01). Nevertheless, only 69% knew specifically the protective role of any type of cleaning. No IDU knew about the use of bleach to clean needles. The HIV prevalence rate among IDUs has increased from 56% to 80%. IDUs in 1993 were more likely to know that HIV is transmitted via sexual intercourse and by needle sharing than in 1990 (95% vs. 70% and 93% vs. 75%, respectively; p 0.01). About 70% of all IDUs in 1993 had undergone HIV testing. Knowing one's HIV status did not influence needle sharing (69.4% vs. 71% for not knowing). Knowledge of HIV transmission, educational status, or history of HIV testing or HIV status influenced unsafe needle sharing practices. When the researchers controlled for education, ethnicity, duration of drug use, and awareness about their HIV test result, only age less than 30 years was associated with sharing of unclean needles (83.4% vs. 16.6% for 30-44 year olds; odds ratio = 2.2; p = 0.0016). These findings suggest urgent and appropriate intervention in this high-risk group.

Epidemiology of Vibrio cholerae O139 with special reference to intrafamilial transmission in Calcutta.

A total of 27 families of hospitalised patients (index case families) suffering from acute watery diarrhoea caused by Vibrio cholerae O139, and 14 neighbourhood families were bacteriologically screened for 4 consecutive days to determine the extent of V. cholerae O139 infection amongst healthy contacts and other suspected vehicles of transmission at the intrafamilial level. V. cholerae O139 was isolated from faeces of 14.6% of healthy contacts in index case families as compared to none in neighbourhood families (P = 0.002). The organism could be recovered from 3.7% of handwashings of contacts of index cases and also from stored drinking water (8.0%), open well water (28.6%), flies (3.8%) and pond water (25.0%) used by the index case families and none from neighbourhood families. The large number of asymptomatic infected persons indicate an epidemiological similarity to that of eltor cholera. The organisms may be carried on hands and may act as a potential source of infection to other inmates through contamination of stored drinking water, open wells etc. The results will be useful in formulating strategies for intervention of transmission of V. cholerae O139 at the community level.

HIV-2 strikes injecting drug users (IDUs) in India.

Manipur, a north-eastern state of India bordering Myanmar, observed introduction of HIV-1 among fairly large number of IDUs in October 1989, followed by rapid spread within the next 6 months. HIV-2 in injectors was not present until recently, though it was detected from other parts of India in 1991. This communication reports for the first time presence of HIV-2 among young injectors of Manipur. All the HIV-2 infected IDUs were also found to be infected with HIV-1. HIV-2 has affected a large number of people in Africa through heterosexual transmission. It remains to be seen whether HIV-2 spreads rapidly also among the drug-injecting population of Manipur. Observation of the disease progression among HIV-2 infected IDUs will also be of interest.

PIP: HIV-1 was first detected in India in 1986. HIV-2 was first detected in the country in 1991 when paid blood donors and STD clinic attenders in north India tested seropositive for the virus. HIV-2 was later detected in Bombay and Goa. HIV-2 was also introduced in Madras and followed by an exponential increase in 1992 where heterosexual transmission was found to be responsible for the spread of the virus. 433 blood samples were collected and screened during the second quarter of 1994 from blood donors, injecting drug users (IDUs), and clinically suspected HIV disease cases admitted to the Regional Medical College (RMC) Hospital or treated at the outpatient department. 60.5% of IDUs tested positive for HIV-1, 6.6% were infected with both HIV-1 and HIV-2, and none were found to be infected exclusively with HIV-2. HIV-infected IDUs were aged 15-35 years and exclusively male. Most clinically suspected cases were young males attending the various departments of RMC with a history of long continued diarrhea, herpes zoster, extreme weight loss, miliary pulmonary tuberculosis, extrapulmonary tuberculosis, or pericardial effusion. Their histories suggested that many were IDUs, while a few only gave histories of unprotected sex with commercial sex workers. The report of a possible link between IDUs of Manipur and Madras suggests that HIV-2 may have come from Madras. The study of dual infection with both HIV-1 and HIV-2 among the IDUs may help in understanding the factors responsible for the efficient transmission of the two viruses. An extensive literature search found that HIV-2 among IDUs has previously been reported only from Spain approximately two years earlier.

Clinical features of HIV infection in drug users of Manipur.

BACKGROUND: The human immunodeficiency virus was first detected in young intravenous drug users in Manipur in 1989 and it quickly reached a high prevalence in this group. Diagnostic facilities are scarce and it is thus important to suspect the presence of the infection by its clinical features. METHODS: We did a cross-sectional survey for 13 months among residents of different detoxification centres of Imphal, Manipur, to study the sensitivity, specificity and positive predictive values of different signs and symptoms occurring at the early phase of the infection. RESULTS: Most of the young injectors in this survey were found to be in the early phases (stage I 43%; stage II 32%; stage III 15% and stage IV 9.9%) of the World Health Organization clinical staging of human immunodeficiency virus infection and disease. Herpes zoster, oral candidiasis, pruritic papular eruptions, jaundice and lymphadenopathy had positive predictive values of 100%, 100%, 93%, 93% and 88% respectively. Cryptosporidial diarrhoea and tuberculosis (pulmonary and extrapulmonary) were also encountered. CONCLUSION: Intravenous drug users in Manipur who have human immunodeficiency virus infection suffer from different opportunistic infections which give rise to clinical features that are easily recognizable. It is important to be aware of these in areas which lack diagnostic facilities for confirming the infection.

PIP: A cross-sectional study conducted among intravenous drug users in India's Manipur State suggests that certain clinical signs and symptoms can be used to detect human immunodeficiency virus (HIV) in areas with scarce diagnostic resources. From May 1992 to April 1993, 154 intravenous drug users recruited from drug detoxification centers in the capital city of Imphal were monitored for clinical manifestations of disease. 131 subjects were HIV-positive, but examining clinicians were not given data on HIV status. All subjects had started injecting within the last seven years, so the majority were in the early phases of HIV. The distribution, by clinical stage, was as follows: I, 43%, II, 32%, III, 15%, and IV, 9.9%). Clinical features most frequently encountered included herpes zoster (27 men), oral thrush (7), pruritic papular eruptions (15), lymphadenopathy (33), and jaundice (14). The positive predictive values of these signs were 100%, 100%, 93%, 88%, and 93%, respectively. Similar studies in other areas are urged to provide information on the sensitivity and specificity of major signs for defining clinical cases of HIV infection.