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Since the emergence of coronavirus disease (COVID-19) in late 2019, domestic cats have been demonstrated to be susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) under natural and experimental conditions. As pet cats often live in very close contact with their owners, it is essential to investigate SARS-CoV-2 infections in cats in a One-Health context. This study reports the first SARS-CoV-2 infection in a cat in a COVID-19-affected household in Switzerland. The cat (Cat 1) demonstrated signs of an upper respiratory tract infection, including sneezing, inappetence, and apathy, while the cohabiting cat (Cat 2) remained asymptomatic. Nasal, oral, fecal, fur, and environmental swab samples were collected twice from both cats and analyzed by RT-qPCR for the presence of SARS-CoV-2 viral RNA. Both nasal swabs from Cat 1 tested positive. In addition, the first oral swab from Cat 2 and fur and bedding swabs from both cats were RT-qPCR positive. The fecal swabs tested negative. The infection of Cat 1 was confirmed by positive SARS-CoV-2 S1 receptor binding domain (RBD) antibody testing and neutralizing activity in a surrogate assay. The viral genome sequence from Cat 1, obtained by next generation sequencing, showed the closest relation to a human sequence from the B.1.1.39 lineage, with one single nucleotide polymorphism (SNP) difference. This study demonstrates not only SARS-CoV-2 infection of a cat from a COVID-19-affected household but also contamination of the cats' fur and bed with viral RNA. Our results are important to create awareness that SARS-CoV-2 infected people should observe hygienic measures to avoid infection and contamination of animal cohabitants., Viruses, 13 (3), ISSN:1999-4915

ObjectivesThe association between obesity and atrial fibrillation (AF) is well-established. We aimed to evaluate the impact of index body mass index (BMI) on AF recurrence at 12 months following catheter ablation using propensity-weighted analysis. In addition, periprocedural complications and fluoroscopy details were examined to assess overall safety in relationship to increasing BMI ranges.MethodsBaseline, periprocedural and follow-up data were collected on consecutive patients scheduled for AF ablation. There were no specific exclusion criteria. Patients were categorised according to baseline BMI in order to assess the outcomes for each category.ResultsAmong 3333 patients, 728 (21.8%) were classified as normal (BMI 2), 1537 (46.1%) as overweight (BMI 25.5–29.0 kg/m2) and 1068 (32.0%) as obese (BMI ≥30.0 kg/m2). Procedural duration and radiation dose were higher for overweight and obese patients compared with those with a normal BMI (p=0.002 and p2led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429; p=0.011), while no significant correlation was found between overweight and normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112).ConclusionsPatients with a baseline BMI ≥30 kg/m2have a higher recurrence rate of AF following catheter ablation and therefore lifestyle modification to target obesity preprocedure should be considered in these patients.

Background Atrial fibrillation (AF) promotes atrial remodeling that in turn promotes AF perpetuation. The aim of our study is to investigate the impact of AF history length on 1-year outcome of AF catheter ablation in a cohort of patients enrolled in the Atrial Fibrillation Ablation Registry. Methods We described the real-life clinical epidemiology, therapeutic strategies, and the short- and mid-term outcomes of 1948 patients (71.9% with paroxysmal AF) undergoing AF ablation procedures, stratified according to AF history duration (= 2 years). Results The mean AF history duration was 46.2 +/- 57.4 months, 592 patients had an AF history duration = 2 years (mean 75.5 +/- 63.5 months) (P < 0.001). Patients with AF history duration = 2 years (34.0%) (P = 0.037). AF history duration >= 2 years, overall ablation procedure duration, hypertension, and chronic kidney disease were all predictors of recurrences after the blanking period. Conclusions In this multicenter registry, performing catheter ablation in patients with an AF history >= 2 years was associated with higher rates of AF recurrences at 1 year. Since cumulative time in AF in not necessarily equivalent to AF history, its role remains to be clarified.

Background Nutrition is an environmental factor affecting bone health. Nutrition is considered essential to achieve and maintain optimal bone mass. Mediterranean diet (MD) has shown to prevent bone disease. Aim of this study is to investigate the relationship between bone health status and adherence the MD. Methods Four-hundred eighteen healthy people (105 males and 313 females, age 50 ± 14 years) were recruited in the outdoor hospital of the “Campus Salute Onlus” held in Piazza del Plebiscito in Naples, October 17–20th 2013 and 09–11th October 2014. All subjects underwent clinical assessment, calcaneal quantitative ultrasound (QUS) scanner and PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. Results Globally, prevalence of osteoporosis and osteopenia were 7.7 and 46.0%, respectively. The majority of subjects (60.5%) had an average score (score 6–9) of adherence to MD. The T-score showed positive correlation with PREDIMED score (r = 0.250, p

Background: Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS. Materials and methods: Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patientswith KS on testosterone therapy (n=48) were also matched against a population of men with treated secondary hypogonadism (n=21). Results: Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reducedmaximal oxygen consumption (p

ContextCDKN1B encodes the cyclin-dependent kinase inhibitor p27Kip1 and is mutated in multiple endocrine neoplasia-like syndromes. CDKN1B also harbors single nucleotide polymorphisms; the T/G transversion at nucleotide 326 (the V109G variant) has been reported to be protective in breast, hereditary prostate, and pancreatic tumors. Association of CDNK1B mutations or polymorphisms with sporadic medullary thyroid carcinoma (MTC) has not been investigated yet.Objective and designWe screened germline DNA from 84 patients affected by sporadic MTC and 90 healthy age- and gender-matched controls for CDKN1B mutations or polymorphisms by PCR amplification and sequencing of the amplicons. We also tested all germline and 50 tumor tissue DNA for RET proto-oncogene mutations. Computed tomography, ultrasound scans, and serum calcitonin were carried out before surgery and during the follow-up and associated with CDKN1B polymorphism and disease remission.ResultsThe T/G transversion at nucleotide 326 was the only DNA variation detected. The overall frequency of the T/G and G/G alleles in combination was 46.4%. This variant (V109G) was correlated with post-operative calcitonin levels in the normal range and biochemical remission. Conversely, the wild-type (T/T) allele was associated with post-operative calcitonin levels above normal and a higher risk to develop clinical recurrence and distant metastases. Somatic RET mutations were significantly associated with a more aggressive behavior especially in wild-type allele-bearing patients.ConclusionsCollectively, in sporadic MTC, the CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker.

A cross-sectional study was performed to determine the prevalence and risk factors for HIV-1 infection among agricultural plantation residents in Kericho, Kenya. Volunteers were recruited, interviewed, and phlebotomized for HIV-1 serologic testing. Sex-specific adjusted odds ratios were estimated using logistic regression. The overall HIV-1 prevalence was 9.9% (81/820), with prevalence in women more than twice that in men (17.4% vs 8.0%, P = 0.001). Among men, elevated HIV-1 prevalence was seen with increasing age, peaking in those older than 30 years (10.3%), marriage (10.4%), Luo tribe affiliation (23.5%), employment (8.9%), travel (11.0%), and being uncircumcised (29.2%). Among women, elevated HIV-1 prevalence was seen in those with no formal education (36.8%) and those who received goods in exchange for sex (36.0%). More than 97% of volunteers expressed a willingness to participate in future HIV-1 studies requiring semiannual visits. HIV prevention efforts have been implemented, along with further research to characterize this population for future cohort feasibility studies and HIV-1 vaccine efficacy trials.

Klinefelter syndrome (KS) is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology generally; nevertheless it seems to be low. We evaluated the need for imaging and serum tumor markers for testicular cancer screening in KS. Participants were 40 consecutive KS patients, enrolled from December 2009 to January 2013. Lactate dehydrogenase (LDH), alpha‐fetoprotein (AFP), and beta‐human chorionic gonadotrophin subunit (‐HCG) serum levels assays and testicular ultrasound (US) with color Doppler, were carried out at study entry, after 6 months and every year for 3 years. Abdominal magnetic resonance (MR) was performed in KS when testicular US showed micro‐calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro‐calcifications and cysts. Eighty seven percent of KS had a regular vascular pattern, 12.5% varicocele, 12.5% nodules 1 cm. MR ruled out the diagnosis of cancer in all KS with testicular micro calcifications, nodules and cysts. No significant variations in LDH, AFP, and ‐HCG levels and in US pattern have been detected during follow‐up. We compared serum tumor markers and US pattern between KS with and without cryptorchidism and no statistical differences were found. We did not find testicular cancer in KS, and testicular US, tumor markers and MR were, in selected cases, useful tools for correctly discriminating benign from malignant lesions.

Intrauterine growth retardation may permanently influence the endocrine system by affecting its programming during development. The aim of this study was to evaluate thyroid and adrenal function together with insulin sensitivity in a group of children born small for gestational age (SGA). Forty SGA children (mean age, 6.7 +/- 1.7 yr) and 35 children born appropriate for gestational age (mean age, 6.5 +/- 2.2 yr) were selected for the study. TSH, free T4, free T3 (fT3), rT3, antithyroid antibodies, cortisol, and dehydroepiandrosterone sulfate (DHEAS) were assessed. Insulin sensitivity was evaluated with the quantitative insulin sensitivity check index (QUICKI). A thyroid ultrasound was also performed in the SGA children. We found that TSH was significantly higher in SGA than in children born appropriate for gestational age [2.9 +/- 1.1 vs. 1.7 +/- 0.7 microU/ml (mIU/liter); P < 0.001]; furthermore, eight SGA children (20%), seven born preterm and one at term, had TSH levels above the upper limit of normality. fT3 was also higher in SGA children (4.2 +/- 0.4 vs. 3.6 +/- 0.6 pg/ml; 6.4 +/- 0.6 vs. 5.5 +/- 0.9 pmol/liter; P < 0.0001), whereas no difference was found for free T4, rT3, and the fT3/rT3 ratio. Urinary iodine was normal, and antithyroid antibodies were absent. Thyroid ultrasound showed a normal echographic pattern with a normal volume in SGA children. Serum cortisol was similar in both groups, whereas DHEAS was significantly lower in SGA subjects (43 +/- 18 vs. 65 +/- 50 microg/dl; 1.1 +/- 0.4 vs. 1.7 +/- 1.3 micromol/liter; P < 0.05). There was no difference in insulin sensitivity between the two groups. Birth length and birth weight were the main determinants of TSH and DHEAS serum levels, respectively. In conclusion, functional thyroid and adrenal changes have been found in children who suffered from intrauterine growth retardation. A larger survey with an appropriate follow-up is, however, required to confirm these findings and to assess their natural evolution.

BACKGROUND: Pubertal gynecomastia is a common problem occurring in up to 65% of adolescent boys. Gynecomastia comes at a time when self-image awareness is at its greatest and psychologically could be a psychologically disabling condition. Surgery is considered the mainstay of treatment for severe or persistent cases. A medical management aimed at altering the effective androgen/estrogen ratio has been suggested with inconstant results. Some promising results have been obtained by using anti-estrogens. Surprisingly there are no data on the estrogen receptor (ER) α and β RNA expression in gynecomastia. AIM: We studied ER RNA subtypes in pubertal gynecomastia. METHODS: ERα and β RNA were determined by real time RT-PCR in 50 mammary samples from pubertal boys with idiopathic gynecomastia subjected to reductive mammoplasty. To study ERα and β pattern of expression, epithelial and stromal primary cell cultures were set up from fresh tissues. RESULTS: These analyses indicated that in all stromal cells ERβ was expressed at higher level than ERα and in epithelial cells both ERα and ERβ were barely detectable. CONCLUSIONS: Our data suggest that also stromal cells are involved in the pathophysiology of pubertal gynecomastia. The high level of expression of ERβ seen in pubertal gynecomastia adds new insight on validation of ERβ as a target for candidate diseases and exploration of ERβ as a marker for clinical decision-making and treatment in pubertal gynecomastia. This could drive to search for new and selective anti-estrogen drugs for medical treatment of pubertal gynecomastia with a particular attention to the ERβ-selective ligand.

CDKN1B encodes the cyclin-dependent kinase inhibitor p27Kip1 and is mutated in multiple endocrine neoplasia-like syndromes. CDKN1B also harbors single nucleotide polymorphisms; the T/G transversion at nucleotide 326 (the V109G variant) has been reported to be protective in breast, hereditary prostate, and pancreatic tumors. Association of CDNK1B mutations or polymorphisms with sporadic medullary thyroid carcinoma (MTC) has not been investigated yet. We screened germline DNA from 84 patients affected by sporadic MTC and 90 healthy age- and gender-matched controls for CDKN1B mutations or polymorphisms by PCR amplification and sequencing of the amplicons. We also tested all germline and 50 tumor tissue DNA for RET proto-oncogene mutations. Computed tomography, ultrasound scans, and serum calcitonin were carried out before surgery and during the follow-up and associated with CDKN1B polymorphism and disease remission. The T/G transversion at nucleotide 326 was the only DNA variation detected. The overall frequency of the T/G and G/G alleles in combination was 46.4%. This variant (V109G) was correlated with post-operative calcitonin levels in the normal range and biochemical remission. Conversely, the wild-type (T/T) allele was associated with post-operative calcitonin levels above normal and a higher risk to develop clinical recurrence and distant metastases. Somatic RET mutations were significantly associated with a more aggressive behavior especially in wild-type allele-bearing patients. Collectively, in sporadic MTC, the CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker.

BACKGROUND: Endocrine gland-derived vascular endothelial growth factor (Prok1) and prokineticin 2 (Prok2) are involved in the organ-specific regulation of angiogenesis, which is a crucial step toward cancer progression in most tumors, including those of thyroid gland. The oncogene BRAF V600E mutation is associated with poor clinical outcome of papillary thyroid cancer (PTC) and can independently predict its recurrence. DESIGN: Our hypothesis was that Prok1 and Prok2 expression levels associated with BRAF mutations can be prognostic factors for PTC outcome. Prok1 and Prok2 were examined in PTC, a cell line derived from a human PTC (designated FB-2), euthyroid multinodular goiter (MNG), Graves' disease (GD), and contralateral normal thyroid (NT) tissues from PTC cases. We evaluated BRAF mutation and its relationship with Prok1 expression pattern in PTC. METHODS: We studied Prok1 and Prok2 mRNAs by real-time polymerase chain reaction and BRAF mutation by mutant allele-specific polymerase chain reaction amplification. Formalin-fixed, paraffin-embedded blocks of PTC and NT were used for the immunohistochemical determination of Prok1 using anti-endocrine gland vascular endothelial growth factor primary antibody. RESULTS: Prok1 and Prok2 transcripts were both present in thyroid tissues, and Prok1 was differentially expressed in PTC compared to MNG, GD, and NT. Prok1 mRNA levels were very low in NT and MNG and significantly higher in PTC, FB-2, and GD (p

HIV-1 subtype B and CRF01_AE have been in circulation in Thailand and Southeast Asia for more than a decade. Initially separated by risk group, the two strains are increasingly intermixed, and two recombinant strains of essentially reciprocal structure have been recently reported. Here we identify additional CRF_01B recombinants and provide the evidence that HIV-1 strains now pass freely between the two high-risk populations. HIV isolates that showed discordance between CRF01_AE and subtype B in multi-region genotyping assays were selected for the study. They were drawn from 3 different cohorts in Thailand representing different risk behaviors and demographic characteristics: a drug user cohort in the north, a family planning clinic attendee cohort in the southeast, and a cohort study of the mucosal virology and immunology of HIV-1 infection in Thailand. The DNA from these isolates was PCR amplified to recover the full HIV-1 genome and subjected to sequencing and phylogenetic analysis. We establish that one particular CRF_01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01_AE, is circulating widely in Thailand. Termed CRF15_01B (also referred to as CRF15), the strain was primarily heterosexually transmitted, although injecting drug use (IDU) also played a role. In aggregate data from the studies, CRF15 constituted 1.7% of all HIV-1 infections (95% confidence interval 0.5-4.4%) and was dispersed widely in the country. The previously separate heterosexual and IDU epidemics have apparently been bridged by a new CRF. The entry of CRF15 into the mainstream of the epidemic signals new complexity in the long stable molecular picture in Thailand. These recombinants must be considered in ongoing or projected efficacy evaluations of HIV-1 vaccines and antiviral therapies.

Objectives: This study examined demographic and geographic correlates of HIV-1 prevalence among civilian applicants for US military service. Methods: HIV-1 test results and demographic and geographic data were available for 5.3 million applicants. Results: Between October 1985 and December 2000, a total of 5,340,694 individuals applied to join one of the armed service branches of the US military. Overall, HIV-1 prevalence was 0.80 per 1000 applicants (95% CI: 0.78-0.82), with 4276 applicants testing positive for HIV-1 infection. Prevalence declined over the 16-year period from a high of 2.89 per 1000 applicants in 1985 to 0.36 per 1000 applicants in 2000. The majority of applicants (82.7%) were male, and the majority of HIV-1 cases (89.4%) occurred in men. HIV-1 prevalence was higher among African Americans (2.47/1000) and Hispanics (0.90/1000) than among white applicants (0.36/1000). HIV-1 prevalence was lowest in the West North Central region of the United States (0.33/1000) and highest in the Middle Atlantic region (1.61/1000) and Puerto Rico (3.56/1000). Conclusions: Civilian applicants for US military service comprise a unique cohort for following trends in the evolving HIV-1 epidemic.

Human immunodeficiency virus type 1 (HIV) RNA load was measured in paired samples of peripheral blood plasma and nasopharyngeal (NP) washes from 97 Thai subjects infected with subtype E or B. HIV RNA was quantifiable in 93% of peripheral blood plasma samples tested and was inversely correlated (ρ =-0.524; p < 0.001) with CD4 absolute count. HIV RNA was quantifiable in 29% of NP samples tested, and the median value was less than that of plasma viral load. HIV RNA load in NP samples was correlated (ρ = 0.388; p < 0.001) with viral load in peripheral blood. HIV RNA was not detected in NP washes from subjects with undetectable plasma viral load. Virus isolation attempts on two NP samples were negative. The results do not support local HIV production in the nasopharynx, but extend current knowledge of HIV shedding to include the NP compartment.

NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW,1500 g at birth). Probiotics including lactobacillus rhamnosus GG (LGG) proved effective in preventing NEC in preterm infants in several RCTs.Lactoferrin, a mammalian milk glycoprotein involved in innate immune host defences, can reduce the incidence of NEC in animal models, and its action is enhanced by LGG. We tried to assess whether bovine lactoferrin (BLF), alone or with the probiotic LGG, has a similar effect in human infants, something that has not yet been studied.An international, multicenter, randomized, double-blind, placebo-controlled trial conducted from October 1st, 2007 through July 31st, 2010.Thirteen Italian and New Zealand tertiary neonatal intensive care units.743 VLBW neonates were assessed until discharge for development of NEC.Infants were randomly assigned to receive orally either BLF (100 mg/day) alone (group LF; n = 247) or with LGG (at 6×10(9) CFU/day; group BLF + LGG; n = 238), or placebo (Control group; n = 258) from birth until day 30 of life (45 for neonates1000 g at birth).≥ stage 2 NEC; death-and/or-≥ stage 2 NEC prior to discharge.Demographics, clinical and management characteristics of the 3 groups were similar, including type of feeding and maternal milk intakes. NEC incidence was significantly lower in groups BLF and BLF + LGG [5/247 (2.0%)] and 0/238 (0%), respectively] than in controls [14/258 (5.4%)] (RR = 0.37; 95% CI: 0.136-1.005; p = 0.055 for BLF vs. control; RR = 0.00; p0.001 for BLF + LGG vs. control). The incidence of death-and/or-NEC was significantly lower in both treatment groups (4.0% and 3.8% in BLF and BLF + LGG vs. 10.1% in control; RR = 0.39; 95% CI: 0.19-0.80; p = 0.008. RR = 0.37; 95% CI: 0.18-0.77; p = 0.006, respectively). No adverse effects or intolerances to treatment occurred.Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death-and/or ≥ stage 2 NEC in VLBW neonates. BLF might be a promising strategy to prevent NEC in NICU settings. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical settings.ISRCTN53107700-http://www.controlled-_trials.com/ISRCTN53107700.

To determine the anticipated participation in a prophylactic AIDS vaccine trial and to identify perceived benefits and barriers to enrollment of HIV-seronegative volunteers at risk of HIV infection in northern Thailand.A cross-sectional survey.Subjects interviewed in a cross-sectional survey included female commercial sex workers (n = 215), men attending sexually transmitted disease clinics (n = 219), conscripts in the Royal Thai Army (n = 1453), and men discharged from the army (n = 293) who had returned to civilian life. We determined AIDS vaccine knowledge and attitudes, perceived vulnerability to HIV infection, barriers and incentives to participate in a future vaccine trial and agreement to participate in a randomized trial.Awareness of vaccines (88-97%) and AIDS vaccine development efforts (62-77%) were common and viewed to be a complement to behavior change (74-94%). Approximately 25% of subjects would definitely join a trial if asked, and an additional 38% would accept an AIDS vaccine if they were convinced it would be safe and effective. Important barriers to participation included concerns with discrimination (16-45%), short- (37-60%) and long-term (30-55%) vaccine side-effects, fear of disability and death (36-58%), and beliefs that partners would refuse to have sex (24-49%) after immunization. The principal inducement to join a trial was health insurance (62%).Potential HIV vaccine trial participants have several fears of joining a vaccine study at this time. Information derived from Phase I/II trials is needed to address these concerns if enrollment in efficacy trials is to be successful in the near future.Thailand has been designated a site for preventive human immunodeficiency virus (HIV) vaccine trials, and Phase I and II trials are currently underway. To assess the feasibility of large-scale Phase III trials involving high-risk individuals, questionnaires were administered to four cohorts of potential participants from North Thailand: 215 female commercial sex workers recruited from sexually transmitted disease (STD) clinics, 219 male STD clients from the same area, 1453 men conscripted into the Royal Thai Army in 1993, and 293 men discharged from the Army in 1993. Approximately 25% of members of each cohort indicated they would definitely join a prophylactic acquired immunodeficiency syndrome (AIDS) trial. The major barriers to participation were concerns about vaccine safety (61% of military cohorts and 32% of civilians) and fear of acquiring AIDS through vaccination (21%). Also expressed were concerns about social discrimination, immediate side effects, and rejection by sexual partner. Two-thirds of respondents indicated that provision of a five-year family health insurance plan would induce them to participate in a vaccine trial, while another 25% did not require any incentive. Overall, these findings indicate that steps must be taken to alleviate fears and misconceptions associated with HIV vaccines before Phase III is initiated.

Despite frequent anemia and multiple transfusions in patients undergoing chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia , recommendations for use of erythropoiesis-stimulating agents (ESAs) in these populations are still missing. The primary objective was the effect of ESA administration on patient's quality of life (QoL). Secondary objectives were hemoglobin (Hb) recovery, red blood cell (RBC) transfusions, overall survival, and event-free survival.Adult patients with Hb ≤ 11 g/dL after consolidation chemotherapy for acute myeloid leukemia (group 1), or after allo-HSCT for any hematological diseases (group 2), were prospectively included. ESA was administered subcutaneously once per week during a maximum period of 6 months and was stopped when Hb level reached 12 g/dL. A paired-matched analysis using a historical control group was performed for secondary endpoints. Fifty-two patients were included in group 1, and 55 patients were in group 2.For the global population, a significant improvement of QoL was noticed with ESA use; 83% (group 1) and 71% (group 2) of patients achieved an Hb level ≥ 12 g/dL without transfusion requirement. The pair-matched analysis showed a reduction of 4 RBC units per patient in group 1 (P = .0002) and 3 RBC units per patient in group 2 (P = .04). No significant difference in terms of thromboembolic events, overall survival, and event-free survival was observed between ESA and control groups. A RBC transfusion median savings of €1712 per patient was estimated in each group.ESAs have a clinical and economic benefit on Hb recovery, could improve a patient's QoL, and lead to a significant reduction in number of RBC transfusions with no effect on survival.

Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants.To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates.Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis.Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates1000 g at birth).First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid.Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P.001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred.Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates.isrctn.org Identifier: ISRCTN53107700.

BACKGROUND. A natural history study of human immunodeficiency virus (HIV) disease was carried out among 1575 HIV-infected US Army men and 6220 demographically similar uninfected soldiers. Inpatient morbidity occurring up to 8 years prior to the date of HIV infection diagnosis among those men who became HIV infected was evaluated for both groups. METHODS. Incidence density rates were calculated for hospital admissions. Poisson regression was used to assess the trend in hospital admissions among those subsequently diagnosed with HIV infection. Prevalence ratios for discharge diagnoses were also calculated. RESULTS. Sixteen diagnoses/diagnosis categories occurred statistically more frequently among subsequently HIV diagnosed individuals than among those who remained uninfected. Among these were hepatitis B and abscess of anal/rectal region (6 to 8 years prior to HIV infection diagnosis); unspecified viral infection, enlarged lymph nodes, syphilis (3 to 5 years prior to HIV infection diagnosis); and diagnoses suggestive of acute retroviral syndrome (1 to 2 years prior to HIV infection diagnosis). CONCLUSIONS. Data such as these may provide useful information to HIV surveillance efforts regarding patterns of morbidity experienced prior to HIV infection as well as to health care providers regarding patients at high risk for becoming infected with HIV.

SUMMARYHuman immunodeficiency virus type 1 (HIV-1) epidemiology among residents of a rural agricultural plantation in Kericho, Kenya was studied. HIV-1 prevalence was 14·3%, and was higher among women (19·1%) than men (11·3%). Risk factors associated with HIV-1 for men were age (⩾25 years), marital history (one or more marriages), age difference from current spouse (⩾5 years), Luo ethnicity, sexually transmitted infection (STI) symptoms in the past 6 months, circumcision (protective), and sexual activity (⩾7 years). Among women, risk factors associated with HIV-1 were age (25–29 years, ⩾35 years), marital history (one or more marriages), age difference from current spouse (⩾10 years), Luo ethnicity, STI symptoms in the past 6 months, and a STI history in the past 5 years. Most participants (96%) expressed a willingness to participate in a future HIV vaccine study. These findings will facilitate targeted intervention and prevention measures for HIV-1 infection in Kericho.

To characterize HIV-1 genotypes in candidate populations for a prime-boost phase III vaccine trial in Thailand, specimens from prevalent and incident HIV-1 infections from a family planning clinic population in Rayong Province and a community cohort in Chon Buri Province, collected from 1998 to 2001, were genotyped. A new multiregion hybridization assay, MHAbce, capable of distinguishing HIV-1 CRF01_AE, subtype B, and subtype C and their recombinants, was developed and applied to prevalent infections. Most incident and selected prevalent infections were studied by complete genome sequencing. By MHAbce, 168 of 194 prevalent infections were genotyped. Of these, 90.5% were CRF01_AE, 2.4% were subtype B, and 7.2% showed discordant or dual probe reactivity, indicative of recombination or dual infection, respectively. Among 23 incident infections, 20 were sequenced. Eighteen CRF01_AE, one subtype B, and one CRF01/B recombinant strains were seen. Two CRF01/B and one CRF01/C recombinant were identified among selected prevalent infections. These results indicate that incident and prevalent HIV-1 infections in Rayong and Chon Buri during 1998-2001 were 90% CRF01_AE, 3% subtype B, and 7% either recombinant or dual. This study frames the genetic diversity of HIV-1 in these cohorts in their preparatory phase for the ongoing ALVACHIV (vCP1521) prime, AIDSVAX B/E boost, phase III vaccine trial and will provide a benchmark for interpretation and analysis.

Objective To monitor HIV-1 infection trends among United States Army personnel, a predominantly young population group, tested between 1985 and 1999 for HIV-1 infection. Design Demographic correlates of HIV-1 infection were assessed in the cohort via epidemiologic analysis. Methods Annual seroconversion incidence rates were calculated per 1000 person-years (PY) of follow-up. Poisson regression was used to assess demographic correlates of HIV-1 seroconversion risk. Results There were 1275 seroconverters among 2 004 903 active duty Army personnel accounting for 7 700 231 PY of follow-up. The HIV-1 incidence rate (IR) was 0.17/1000 PY [95% confidence interval (CI), 0.16–0.17]. The highest IR was observed in the first year of testing (IR, 0.43/1000 PY; 95% CI, 0.33–0.52). The IR for male and female soldiers was 0.18/1000 PY and 0.08/1000 PY, respectively. HIV-1 incidence declined with age. Significant risk of HIV-1 seroconversion was associated with age [> 30 years old relative risk (RR), 1.51], race (Black RR, 4.61; Hispanic RR, 2.76), gender (male RR, 3.12), marital status (unmarried RR, 2.01) and rank (enlisted RR, 2.50). Conclusions HIV-1 seroconversions in the US Army have been low and stable since the early 1990s. Continued HIV-1 incidence surveillance in the US Army provides information on the status of the epidemic in the Army, as well as important corroborative data on HIV-1 infections throughout the US.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

Experimental data suggest an involvement of immune cellular components in the development of Alzheimer''s disease (AD). Against this background, the spontaneous natural killer (NK) cell activity and the NK-induced cytotoxicity after interleukin-2 (IL-2) were studied in healthy elderly subjects and in patients with dementia of Alzheimer type (SDAT) and multi-infarct type (MID). Higher NK cytotoxicity (expressed as total lysis and percent increase) at different IL-2 concentrations (50 and 100 IU/ml/cells) was demonstrated in patients with SDAT than in healthy elderly subjects (p < 0.001) and MID patients (p < 0.001). NK cell activity of MID patients was similar to that of healthy elderly and healthy young subjects. A negative correlation between the percent increase in NK cytotoxicity after IL-2 and the Mini Mental State Examination Score was also found in SDAT patients (p < 0.01). Alterations of IL-2-mediated NK cytotoxicity may therefore support the neuroimmune hypothesis of AD.

The direct measurement of the incidence of new infections with the human immunodeficiency virus type 1 (HIV-1) can be made among soldiers because of the routine and periodic nature of HIV-1 testing in the United States Army. Between November 1985 and October 1993, 978 HIV-1 seroconversions were seen among 1,061,768 soldiers, contributing over 3.6 million person-years of follow-up [seroconversion rate (95% confidence interval) = 0.27/1,000 person-years (0.25-0.29)]. A significant decreasing trend in HIV-1 seroconversion rates was seen over the analysis period. The rate of new infections declined significantly from the first interval, 1985-1987, (0.43/1,000 person-years) to the second interval, 1987-1988, (0.28/1,000 person-years), but stabilized at approximately 0.22/1,000 person-years after 1988, representing new infections in approximately 100-150 soldiers annually. The risk of seroconversion among active duty soldiers was significantly associated with racial/ethnic group, age, gender, and marital status. Surveillance of HIV-1 seroconversion rates in the U.S. Army continues to offer a unique opportunity to assess temporal trends in the evolving HIV-1 infection epidemic. Monitoring the rate of new HIV-1 infections allows for identification of subgroups in need of intervention, refocusing of intervention strategies, and evaluation of their effectiveness.

Because soldiers in the US Army are recurrently tested for the presence of antibody to the human immunodeficiency virus (HIV), HIV seroconversion rates can be directly measured. From November 1985 through October 1989, 429 HIV seroconversions were detected among 718,780 soldiers who contributed 1,088,447 person-years of follow-up time (HIV seroconversion rate, 0.39 per 1000 person-years). Period-specific seroconversion rates declined significantly from 0.49 per 1000 person-years (November 1985 through October 1987) to 0.33 per 1000 person-years (November 1987 through October 1988) to 0.29 per 1000 person-years (November 1988 through October 1989). The HIV seroconversion risk among active-duty soldiers was significantly associated with race/ethnic group, age, gender, and marital status. Based on these trends, we estimate that approximately 220 soldiers (95% confidence interval, 160 to 297 soldiers) were infected with HIV during 1989 and 1990, with potentially fewer in future years.

A large proportion of human immunodeficiency virus antibody (HIV-Ab) positive male soldiers are considered to be at no identified risk (NIR) because they do not disclose histories of sexual activity with other men, intravenous drug use, blood transfusions, or sexual activity with persons at known high risk for HIV infection. A case-control study involving personal interviews with 26 NIR cases and 74 controls was conducted to determine if lifestyle information that might jeopardize a soldier's military career could be obtained from an Army population and to evaluate risk factors for prevalent HIV infection. Subjects consented to a voluntary, anonymous, and confidential interview containing information on demographic characteristics, medical history, drug use, and sexual behavior. Of 26 cases interviewed, 20 (76.9%) reported behaviors defined by the Centers for Disease Control (CDC) as risk factors for HIV infection, while 11 of 74 (14.9%) controls also reported such behaviors. This proportion of reclassified NIR cases was similar to that reported from the NIR case series study conducted by the CDC. Of the six (23.1%) cases who remained at NIR, all reported at least one of the following risks: a history of sexually transmitted diseases, sexual contact with prostitutes, or sexual activity with female partners which caused bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)