Characterization of antimicrobial resistance of recent Salmonella enterica serovar Gallinarum isolates from chickens in South Korea.
Salmonella enterica serovar Gallinarum isolates (n=105) from chickens in South Korea between 2002 and 2007 were tested for antimicrobial susceptibility by determining minimum inhibitory concentrations of 16 antimicrobials, and their predominant resistance profiles were genetically characterized. Most isolates (99/105; 94.3%) were resistant to nalidixic acid and resistant/intermediately resistant to fluoroquinolones, and 63.8% (67/105) of the isolates were resistant to three or more antimicrobials. Forty-two quinolone-resistant isolates, of which the quinolone resistance-determining regions of the gyrA genes were sequenced, contained a substitution of a Ser to a Phe or Tyr at position 83 (71.4%), or a substitution of an Asp to an Asn, Gly, or Tyr at position 87 (28.6%). Fifty-seven sulphamethoxazole-resistant isolates were tested for the presence of class 1 integrons by polymerase chain reaction, and their resistance gene cassettes were analysed by sequencing. Three different class 1 integrons containing the resistance-gene insert aadA (52.6%; n=30), aadB (12.3%; n=7), or aadB-aadA (12.3%; n=7) were identified. Most isolates harbouring the integron containing aadB-aadA displayed resistance to all three aminoglycosides tested and also showed increased resistance to fluoroquinolones. These findings suggest that fluoroquinolone resistance may be epidemiologically linked to multiple aminoglycoside resistance.


Bone marrow edema is the most specific finding for rheumatoid arthritis (RA) on noncontrast magnetic resonance imaging of the hands and wrists: a comparison of patients with RA and healthy controls.
To evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) in detecting erosions, bone edema, and synovitis in the metacarpophalangeal and wrist joints for rheumatoid arthritis (RA). MRI scans of bilateral hands and wrists of 40 healthy subjects and 40 RA patients were performed using 0.2 T extremity-MRI and read blindly using a modified RA MRI (RAMRIS) system (no contrast injection, imaging in 1 plane only). To determine interreader reliability, images of 10 randomly selected subjects were read independently by a musculoskeletal radiologist. A total of 3360 bones were evaluated. Patients with RA had significantly more erosions as well as higher scores for bone edema and synovitis than healthy subjects. Age had a significant effect on the number of erosions in both groups. However, when disease duration was factored in, age became insignificant in RA patients. Erosion number correlated with positive rheumatoid factor and higher C-reactive protein values. The intraclass correlation coefficient between the 2 readers was 0.76 for individual joints and 0.88 for total scores. When having a single erosion was used as a positive test for RA, the sensitivity of this test was 90%, but the specificity was only 35%. Presence of bone edema provided 65% sensitivity and 82.5% specificity. Eliminating the lunate from scoring for bone edema increased the specificity to 87.5% while decreasing the sensitivity to 62.5%. While MRI is a highly sensitive tool for identifying and tracking the progression of erosions, erosions detected by MRI with measures commonly used in a rheumatologist's office (no contrast, imaging in 1 plane) provide low specificity for RA. Bone marrow edema is the most specific MRI lesion for RA in this setting.


Two regimens of azithromycin prophylaxis against community-acquired respiratory and skin/soft-tissue infections among military trainees.
Epidemics of community-acquired pneumonia (CAP) are a frequent cause of morbidity among Russian military trainees. We evaluated azithromycin prophylaxis against CAP. In 2001-2002, incoming military trainees were randomized to 1 of 3 trial arms by training group: azithromycin, 500 mg per week for 8 weeks (R1); azithromycin, 1500 mg once at enrollment (R2); or no therapy (R3). During the 22 weeks of training, CAP was diagnosed in 20.2% of 678 subjects in the R3 group, 8.6% of 508 subjects in the R1 group, and 10.3% of 507 subjects in the R2 group. Throat carriage cultures revealed that the proportion of Streptococcus pneumoniae isolates with resistance to macrolides correspondingly increased during the study, from 0% (all) to 40% (R1) and 22.6% (R2) by week 20. Azithromycin prophylaxis is effective against CAP in a healthy population of young men at transient high risk of disease; however, azithromycin use must be tempered with the possible concomitant risk of selection for resistant endemic pathogens.


[Capture and detection of human cytomegalovirus (HCMV) IgM by a recombinant multi-epitope chimeric antigen].
To establish a sensitive and specific antibody-capture enzyme-linked immunosorbent assay (AC-ELISA) method to detect serum IgM against human cytomegalovirus (HCMV) by expressing a recombinant HCMV multi-epitope cheimeric antigen through genetic engineering. The dominant epitopes of HCMV were analyzed and selected by computer software A recombinant multi-epitope chimeric antigen expression vector including HCMV DNA was constructed, and transformed into E. coli BL21(DE3). The antigen was abundantly expressed, purified, and labeled by horseradish peroxidase for subsequent development of the AC-ELISA. Thirty validated positive sera and sixty-three validated negative sera were submitted for IgM detection by this recombinant antigen. The sensitivity and specificity of AC-ELISA with our recombinant antigen were both 100%. The sensitivity and specificity of this AC-ELISA diagnostic kit with the recombinant antigen are comparable to similar foreign commercial products.


Comparative effectiveness of a fixed-dose combination of losartan + HCTZ versus bisoprolol + HCTZ in patients with moderate-to-severe hypertension: results of the 6-month ELIZA trial.
The aim of this study was to compare the antihypertensive efficacy of losartan 100 mg + hydrochlorothiazide (HCTZ) 25 mg versus bisoprolol 10 mg + HCTZ 25 mg and their influence on arterial stiffness and central blood pressure (BP). Of 60 patients with a mean BP of 173.3 ± 1.7/98.4 ± 1.2 mmHg, 59 were randomized to losartan + HCTZ (n = 32) or bisoprolol + HCTZ (n = 27). Amlodipine was added if target BP was not achieved at 1 month, and doxazosin was added if target BP was not achieved after 3 months. Body mass index, office and 24-hour ambulatory BP, pulse wave velocity (carotid-femoral [PWVE] and radial [PWVM]), noninvasive central systolic BP, augmentation index (AIx), laboratory investigations, and electrocardiography were done at baseline and after 6 months of treatment. Losartan + HCTZ was as effective as bisoprolol + HCTZ, with target office BP achieved in 96.9% and 92.6% of patients and target 24-hour BP in 75% and 66.7% of patients, respectively, after 6 months. Effective treatment of BP led to significant lowering of central systolic BP, but this was decreased to a significantly (P < 0.05) greater extent by losartan + HCTZ (-23.0 ± 2.3 mmHg) than by bisoprolol + HCTZ (-15.4 ± 2.9 mmHg) despite equal lowering of brachial BP. Factors correlated with central systolic BP and its lowering differed between the treatment groups. Losartan + HCTZ did not alter arterial stiffness patterns significantly, but bisoprolol + HCTZ significantly increased AIx. We noted differences in ΔPWVE, ΔPWVM, and ΔAIx between the groups in favor of losartan + HCTZ. Decreased heart rate was associated with higher central systolic BP and AIx in the bisoprolol + HCTZ group, but was not associated with increased AIx in the losartan + HCTZ group. Although both treatments decreased both office and 24-hour BP, losartan + HCTZ significantly decreased central systolic BP and had a more positive influence on pulse wave velocity, with a less negative effect of decreased heart rate on AIx and central systolic BP.


Lower Density and Shorter Duration of Nasopharyngeal Carriage by Pneumococcal Serotype 1 (ST217) May Explain Its Increased Invasiveness over Other Serotypes.
Streptococcus pneumoniae is a frequent colonizer of the human nasopharynx and a major cause of life-threating invasive infections such as pneumonia, meningitis and sepsis. Over 1 million people die every year due to invasive pneumococcal disease (IPD), mainly in developing countries. Serotype 1 is a common cause of IPD; however, unlike other serotypes, it is rarely found in the carrier state in the nasopharynx, which is often considered a prerequisite for disease. The aim of this study was to understand this dichotomy. We used murine models of carriage and IPD to characterize the pathogenesis of African serotype 1 (sequence type 217) pneumococcal strains obtained from the Queen Elizabeth Central Hospital in Blantyre, Malawi. We found that ST217 pneumococcal strains were highly virulent in a mouse model of invasive pneumonia, but in contrast to the generally accepted assumption, can also successfully establish nasopharyngeal carriage. Interestingly, we found that cocolonizing serotypes may proliferate in the presence of serotype 1, suggesting that acquisition of serotype 1 carriage could increase the risk of developing IPD by other serotypes. RNA sequencing analysis confirmed that key virulence genes associated with inflammation and tissue invasiveness were upregulated in serotype 1. These data reveal important new insights into serotype 1 pathogenesis, with implications for carriage potential and risk of invasive disease through interactions with other cocolonizing serotypes, an often-overlooked factor in transmission and disease progression.IMPORTANCE The pneumococcus causes serious diseases such as pneumonia, sepsis, and meningitis and is a major cause of morbidity and mortality worldwide. Serotype 1 accounts for the majority of invasive pneumococcal disease cases in sub-Saharan Africa but is rarely found during nasopharyngeal carriage. Understanding the mechanisms leading to nasopharyngeal carriage and invasive disease by this serotype can help reduce its burden on health care systems worldwide. In this study, we also uncovered the potential impact of serotype 1 on disease progression of other coinfecting serotypes, which can have important implications for vaccine efficacy. Understanding the interactions between different serotypes during nasopharyngeal carriage may lead to improved intervention methods and therapies to reduce pneumococcal invasive disease levels.


Advances in cardiovascular genetics and embryology: role of transcription factors in congenital heart disease.
In spite of tremendous advances in diagnosis and treatment of cardiovascular disease in the young, our understanding of its cause is still incomplete. Recent studies have reported pleiotropic cardiac malformations resulting from mutations in transcription factors, a family of proteins known to play important roles in many aspects of development. Further evaluation of these important causes of cardiovascular disease in the young promises new insight into embryology of cardiac development and improved understanding of the pathophysiologic basis of cardiovascular disease in the young.


Hounsfield Units: a new indicator showing maxillary resistance in rapid maxillary expansion cases?
To determine if density measurements of several maxillary regions in Hounsfield Units (HU) and outcomes of rapid maxillary expansion (RME) are correlated. Is correlation powerful enough to give us direct information about maxillary resistance to RME? Twenty-two computed tomographic (CT) scans (14 years) are used in this archive study. Two CT records were collected, one before RME (T1) and one after 3 months of retention period (T2). Maxillary measurements were made using dental and skeletal landmarks in first molar and first premolar slides to measure the effects of RME. Density of midpalatal suture (MPSD) and segments of maxillary bone is measured in HU at T1. Correlation analysis was conducted between density measurements and maxillary variables. Regression analysis was then performed for variables that showed positive correlation. There was no correlation between density and skeletal measurements. Intermolar angle (ImA) in molar slice showed statistically significant correlation with density measurements. The ImA variable showed the highest correlation with MPSD in frontal section (r = 0.669, P < .01). There is correlation of 32.1-43.3% between density measurements and ImA increase. Our density measurements explain a certain percentage of ImA increase, but density is not the only and definitive indicator of changes after RME.


Immunological aspects of nematode parasite control in sheep.
Gastrointestinal nematode parasitism is arguably the most serious constraint affecting sheep production worldwide. Economic losses are caused by decreased production, the costs of prophylaxis and treatment, and the death of the infected animals. The nematode of particular concern is Haemonchus contortus, which can cause severe blood loss resulting in anemia, anorexia, depression, loss of condition, and eventual death. The control of nematode parasites traditionally relies on anthelmintic treatment. The evolution of anthelmintic resistance in nematode populations threatens the success of drug treatment programs. Alternative strategies for control of nematode infections are being developed, and one approach is to take advantage of the host's natural or acquired immune responses, which can be used in selection programs to increase the level of resistance in the population. Vaccination can also be used to stimulate or boost the host's acquired immunity. The induction of protective resistance is dependent on the pattern of cytokine gene expression induced during infection by two defined CD4+ T-helper cell subsets, which have been designated as Th1 or Th2. Intracellular parasites most often invoke a Th1-type response, and helminth parasites a Th2-type response. Breeds of sheep resistant to infection have developed resistance over a much longer term of host-parasite relationship than genetically selected resistant lines. The immune components involved in these different responses and types of host-parasite relationships will be reviewed. The potential for using vaccines has been investigated, with variable results, for several decades. The few successes and potential new antigen candidates will also be reviewed.


SRSFs mediate the function of AR in the ovarian granulosa cells of patients with PCOS.
Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome (PCOS) and androgen receptor (AR) in ovarian granulosa cells (GCs) functions as an important element to the accumulation of androgens. This study verified the existence of alternative splicing variant of AR (AR-SVs) in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs. And compared to the normal individuals, the expression of Serine/arginine-rich splicing factor 2(SRSF2) was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs. More importantly, we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183, and testostrone (T) concentrations in the culture medium were increased. The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated, while the expression of AR significantly increased; however, the function of AR was also inhibited when T concentration in the culture medium was increased. This study has proved that SRSFs are regulated by corresponding miRNAs, and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR, leading to the accumulation of androgens in the ovary.


Potential mechanisms of hypocholesterolaemic effect of Thai spices/dietary extracts.
Several Thai spices/dietary ingredients were previously shown to have hypocholesterolaemic effects. These studies were mostly conducted in animal models in which the mechanisms of action were not yet well-established. Therefore, this study aimed to investigate the potential mechanism of hypocholesterolaemic action of 12 selected plants, namely Hibiscus sabdariffa L., Moringa oleifera Lam., Cucurbita moschata Duchesne, Ananas comosus (L.) Merr., Zingiber officinale, Morus alba L., Camellia sinensis (L.) Kuntze, Piper nigrum L., Alpinia galanga (L.) Willd., Curcuma zedoaria Rose, Bacopa monnieri (L.) Wettst. and Piper retrofractum Vahl., widely used as spices and ingredients in various types of Thai food. The extract of P. nigrum at 100 µg mL(-1) was found to be the most effective cholesterol uptake inhibitor whereas those of A. galanga and C. sinensis effectively inhibited pancreatic lipase activity with IC50 values of 8.99±3.41 and 12.36±1.23 µg mL(-1), respectively. The potency of extracts from H. sabdariffa, M. oleifera and C. moschata at 100 µg mL(-1) were found to be similar to 0.4 µg mL(-1) pravastatin in inhibiting HMG-CoA reductase and possibly reduced cholesterol biosynthesis. This study also demonstrated that several of the tested plants possessed multiple sites of action that were possibly responsible for their cholesterol-lowering effect in the in vivo model.


The Association Between Objectively Measured Vision Impairment and Self-Reported Physical Activity Among 34,129 Adults Aged ≥50 Years in Six Low- and Middle-Income Countries.
The authors investigated the association between vision impairment and physical activity among older adults from low- and middle-income countries. Visual acuity was measured using the tumbling ElogMAR chart, and vision impairment was defined as visual acuity worse than 6/18 (0.48 logMAR) in the better seeing eye. Physical activity was assessed by the Global Physical Activity Questionnaire. Multivariable logistic regression and meta-analysis were conducted to assess associations. The sample included 34,129 individuals aged 50-114 years (mean [SD] age 62.4 [16.0] years; 47.9% male). After adjustment for confounders, near vision impairment was not significantly associated with low physical activity, but far vision impairment showed a significant association (odds ratio = 1.32; 95% confidence interval [1.17, 1.49], I2 = 0.0%). Far vision impairment was dose-dependently associated with low physical activity (e.g., severe [<6/10] vs. no [≥6/12] far vision impairment; odds ratio = 1.80; 95% confidence interval [1.03, 3.15]). Interventions to address low levels of physical activity in the visually impaired in low- and middle-income countries should target those with far vision impairment.


Expression of mt1 melatonin receptor in rat retina: evidence for multiple cell targets for melatonin.
Melatonin is synthesized in the retina at night and acts as a local modulator within this tissue by mediating the effects of darkness. We investigated the expression and localization of the mt1 (Mel1a) melatonin receptor in rat retina in order to disclose the cellular and molecular bases of melatonin's action in the mammalian retina. Western blotting of the mt1 receptor in rat retina exhibited a single immunoreactive band of approximately 37,000 mol. wt, which corresponds to the predicted molecular size of the receptor. The mt1 receptor was immunocytochemically localized to both the inner and outer plexiform layers. During postnatal development, retina from two-week-old rats showed the highest mt1 immunoreactivity; the outer plexiform layer and horizontal cell bodies were strongly immunolabeled, with weaker labeling in the inner plexiform layer. Expression of mt1 receptor messenger RNA in the rat retina was demonstrated by reverse transcription-polymerase chain reaction and in situ hybridization. mt1 receptor transcripts were localized to ganglion cells, amacrine cells and horizontal cells. These results suggest that melatonin influences retinal physiology by acting on multiple retinal cell types, including ganglion, amacrine and horizontal cells, via the mt1 receptor expressed in their processes.


The distribution of enteric bacteria from Australian mammals: host and geographical effects.
Bacteria of the family Enterobacteriaceae were isolated from 642 mammalian hosts, representing 16 families and 79 species, collected from throughout Australia. Escherichia coli was the most common of the 24 enteric species recovered and represented almost half of the isolates. Association analysis revealed that most other species of bacteria were less likely to be recovered from hosts in which E. coli was present. The composition of the enteric community of a host was found to be determined by both the taxonomic family to which the host belonged and the geographical area from which the host was collected. Hosts collected from the northern areas of Queensland and the Northern Territory had more diverse enteric communities than hosts collected from New South Wales or Western Australia. Hosts of the families Petauridae and Vespertilionidae had more diverse enteric communities than did members of the Macropodidae or Phalangeridae. The probability of occurrence of Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Hafnia alvei, Klebsiella oxytoca and K. pneumoniae in a host was found to vary with respect to host family and/or host locality. The non-random distribution of these species demonstrates the presence of extensive population structure and may suggest the existence of adaptations specific to both the primary and secondary habitats of these enteric bacteria.


Association of strong virus-specific CD4 T cell responses with efficient natural control of primary HIV-1 infection.
To investigate whether there are differences in the virus-specific CD4 T cell response during primary HIV-1 infection in patients who naturally (without antiretroviral intervention) control viral replication with differing efficiencies. CD4 T cell responses to recombinant HIV proteins (Gag p24 and p55 and Env gp160) and an inactivated HIV-1 preparation were analysed using interferon-gamma ELISPOT assays (with CD8-depleted peripheral blood mononuclear cells) and by intracellular interferon-gamma staining and fluorescent-activated cell sorting. Strong HIV-specific CD4 T cell responses were detected from the earliest time-points analysed in primary infection in patients who naturally established low persisting viral loads. By contrast, HIV-specific CD4 T cell responses were weaker (at or just below the limit of detection in our assays) at similar time-points in patients who went on to establish high persisting viral loads. Statistical analysis revealed a highly significant difference (P < 0.001) between the magnitudes of the Gag p24-specific response at the earliest time-point analysed in primary infection in the two sets of patients. Strong HIV-specific CD4 T cell responses are associated with efficient natural control of primary HIV-1 infection.


[Autodermoplasty in postoperative hernias].
Autodermal hernioplasty was used in 102 patients. The transplant was treated by heating through a napkin moistened in the physiologic salt solution. Two methods of hernioplasty are proposed for approximated and nonapproximated margins of the hernia hilus. In both cases the flap was placed with its reticular layers directed towards the muscular-aponeurotic plates, being disposed under them. A small amount of wound complications and the absence of recurrences show the efficiency of the proposed methods of autodermal plasty.


Effect of photobiomodulation in secondary intention gingival wound healing-a systematic review and meta-analysis.
Photobiomodulation is widely being used to improve the wound healing process in dentistry and a vast majority of studies have proven its benefits. But there are plenty of knowledge gaps according to the optimal laser characteristics which should be used to maximize the healing effects of lasers. The goal of this systematic review and meta-analysis was to determine the effect of photobiomodulation (PBM) as an adjunctive treatment to periodontal therapies to evaluate secondary intention gingival wound healing and post-operative pain. Five databases (PubMed, Embase, Scopus, ProQuest, and Web of Sciences) were searched up to November 30, 2020, for clinical trials that reported the result of the application of PBM on secondary gingival healing wounds and post-operative pain and discomfort after periodontal surgeries. Two independent reviewers selected the eligible studies and the outcomes of interest were extracted. The quality of eligible studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Ultimately, twelve studies were included in this review. The application of PBM as an adjunct to periodontal surgeries resulted in a significant improvement in wound healing indices. The Landry wound healing index at the 7th post-operative day was significantly improved (SMD = 1.044 [95% CI 0.62-1.46]; p < 0.01) in PBM + surgery groups compared to the control groups. There was also a statistically significant increase in the complete wound epithelialization (RR = 3.23 [95% CI 1.66-6.31]; p < 0.01) at the 14th post-operative day compared to the control groups. The methods used to assess the post-operative pain were heterogeneous, and therefore the results were limited which made the meta-analysis for post-operative pain assessment not possible. Based on the results of this review, PBM can be effectively used as a method to improve secondary intention wound healing. High-quality randomized clinical trials, however, are needed in the future to identify the optimal PBM irradiation parameters and the effect of PBM on post-operative pain.


Escitalopram: better treatment for depression is through the looking glass.
Depression remains a common and often devastating illness. With the introduction of the selective serotonin reuptake inhibitors in the 1980s, patients were afforded treatment for depression that was both safer and better tolerated than any prior treatment modality offered. Although selective serotonin reuptake inhibitors quickly became the most widely used medications for the treatment of depression, no single agent has been recognized as an obvious first-line choice. Chirality potentially offers one method to improve upon the selective serotonin reuptake inhibitor class. For racemic compounds that differ in stereospecificity, separation into single enantiomers can result in significant changes in potency, tolerability and efficacy. One of the most widely prescribed selective serotonin reuptake inhibitors is citalopram, which exists as a racemic mixture of R- and S-enantiomers. The S-enantiomer escitalopram (Cipralex, Lundbeck) is the therapeutically active portion of the parent compound and has a proven antidepressant efficacy. The R-enantiomer lacks activity as an antidepressant and has been shown to inhibit the effect of the S-enantiomer when the two are combined. Escitalopram is the most selective member of its class and with minimal effects on the cytochrome P450 system, has a negligible potential for drug-drug interactions. In placebo-controlled trials, escitalopram has consistently demonstrated symptomatic improvement as early as the first to second week of treatment. In addition to antidepressant efficacy, escitalopram also appears to exhibit significant anxiolytic properties. It has also shown efficacy in treating panic disorder and generalized and social anxiety disorders. This is advantageous as many patients who suffer from depression also experience comorbid anxiety disorders.


Effect of dihydrofolate reductase gene knock-down on the expression of heart and neural crest derivatives expressed transcript 2 in zebrafish cardiac development.
Folic acid is very important for embryonic development and dihydrofolate reductase is one of the key enzymes in the process of folic acid performing its biological function. Therefore, the dysfunction of dihydrofolate reductase can inhibit the function of folic acid and finally cause the developmental malformations. In this study, we observed the abnormal cardiac phenotypes in dihydrofolate reductase (DHFR) gene knock-down zebrafish embryos, investigated the effect of DHFR on the expression of heart and neural crest derivatives expressed transcript 2 (HAND2) and explored the possible mechanism of DHFR knock-down inducing zebrafish cardiac malformations. Morpholino oligonucleotides were microinjected into fertilized eggs to knock down the functions of DHFR or HAND2. Full length of HAND2 mRNA which was transcribed in vitro was microinjected into fertilized eggs to overexpress HAND2. The cardiac morphologies, the heart rates and the ventricular shortening fraction were observed and recorded under the microscope at 48 hours post fertilization. Whole-mount in situ hybridization and real-time PCR were performed to detect HAND2 expression. DHFR or HAND2 knock-down caused the cardiac malformation in zebrafish. The expression of HAND2 was obviously reduced in DHFR knock-down embryos (P < 0.05). Microinjecting HAND2 mRNA into fertilized eggs can induce HAND2 overexpression. HAND2 overexpression rescued the cardiac malformation phenotypes of DHFR knock-down embryos. DHFR plays a crucial role in cardiac development. The down-regulation of HAND2 caused by DHFR knock-down is the possible mechanism of DHFR knock-down inducing the cardiac malformation.


Photodynamic Therapy for Colorectal Cancer: A Systematic Review of Clinical Research.
Photodynamic therapy (PDT) is a therapeutic modality that can be used to ablate tumors using the localized generation of reactive oxygen species by combining a photosensitizer, light, and molecular oxygen. This modality holds promise as an adjunctive therapy in the management of colorectal cancer and could be incorporated into neoadjuvant treatment plans under the auspices of prospective clinical trials. We conducted a search of primary literature published until January 2021, based on PRISMA guidelines. Primary clinical studies of PDT for the management of colorectal cancer were included. Screening, inclusion, quality assessment, and data collection were performed in duplicate. Analyses were descriptive or thematic. Nineteen studies were included, most of which were case series. The total number of patients reported to have received PDT for colorectal cancer was 137, almost all of whom received PDT with palliative intent. The most common photosensitizer was hematoporphyin derivative or Photofrin. The light dose used varied from 32 J/cm2 to 500 J/cm2. Complete tumor response (cure) was reported in 40%, with partial response reported in 43.2%. Symptomatic improvement was reported in 51.9% of patients. In total, 32 complications were reported, the most common of which was a skin photosensitivity reaction. PDT for the management of colorectal cancer has not been well studied, despite promising results in early clinical case series. New, well designed, prospective clinical trials are required to establish and define the role of PDT in the management of colorectal cancer.


Genetic instability of R plasmids in relation to the shift of drug resistance patterns in Salmonella johannesburg.
Observation of the resistance of Salmonella johannesburg to the six drugs ampicillin (A), streptomycin (S), tetracycline (T), chloramphenicol (C), kanamycin(K) and sulphadiazine (Su) was made over the 7 years from 1973 to 1979. Strains with ASTCKSu- and ASCKSu- resistance patterns predominated in the years 1973-1975 and 1976-1979, respectively. These resistances were found to be mediated by autotransferring plasmids belonging to the incompatibility group FIme. The ASTCKSu-resistance plasmids were unstable, giving rise to deletion variants at a much higher frequency than ASCKSu-resistance plasmids either of natural origin or derived in vitro from the ASTCKSu-resistance plasmids. Thus, the ASCKSu-resistance plasmid might be a deletion variant of the ASTCKSu-resistance plasmid. This is supported by the extensive similarity of their cleavage patterns produced by specific restriction endonucleases.


Toxicological assessment of minoxidil: A drug with therapeutic potential besides alopecia.
Minoxidil is regularly prescribed for alopecia, and its therapeutic potential has expanded in recent times. However, few studies have been conducted to evaluate its toxicity, and controversial findings regarding its mutagenic activities remain unsolved. This study aimed to access cytotoxic, genotoxic, and mutagenic properties of minoxidil using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, comet assay, and micronucleus test in mouse fibroblast (L929) cells and its point mutation induction potential in the Salmonella/microsome assay. Furthermore, an in vivo toxicity assessment was conducted in Caenorhabditis elegans. Minoxidil showed cytotoxicity at 2.0 mg/mL in MTT assay. Genotoxicity was observed after 3 h treatment in L929 cells using comet assay. No mutagenic effect was observed in both the micronucleus test and the Salmonella/microsome assay. The lethal dose 50 in C. elegans was determined to be 1.75 mg/mL, and a delay in body development was detected at all concentrations. In conclusion, minoxidil induces DNA damage only in early treatment, implying that this DNA damage may be repairable. This observation corroborates the absence of mutagenic activities observed in L929 cells and Salmonella typhimurium strains. However, the toxicity of minoxidil was evident in both C. elegans and L929 cells, underscoring the need for caution in its use.


[Structured care for stroke patients: stroke units and transmural stroke services].
Following the successful introduction of Coronary Care Units for patients after a myocardial infarction, Stroke Units were designed where the specialized care for patients who had suffered a stroke might be concentrated. A meta-analysis in 1993 indicated that patients indeed benefited from treatment in such a unit. Stroke is the third cause of death in the Netherlands, with a prevalence in people aged 55 and more of 3.5% in men and of 1.9% in women. A Stroke Unit is part of a hospital; a Transmural Stroke Service in which neurologists and general practitioners participate, may deliver the appropriate care in the appropriate setting: patients may quickly be admitted to the hospital, an outpatient clinic can limit unnecessary hospitalization, and the general practitioner supervises chronic home treatment. The possibilities are there, now they have to be implemented.


Alteration in the activities of the membrane-integrated enzymes of polymorphonuclear leukocytes in obesity.
Oubain sensitive and insensitive adenosine triphosphatase showed decrease in their activities in the polymorphonuclear leukocytes of obese patients while the activity of acetylcholinesterase was found to be increased significantly. The contents of sodium, potassium and magnesium were found to be significantly decreased in polymorphonuclear leukocytes of obese patients. Polymorphonuclear leukocytes obtained from treated obese patients showed considerable restoration.


ELOVL5 mutations cause spinocerebellar ataxia 38.
Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456 independent SCA-affected individuals identified the same mutation in two further unrelated Italian families. Haplotyping showed that at least two of the three families shared a common ancestor. One further missense variant (c.214C>G [p.Leu72Val]) was found in a French family. Both missense changes affect conserved amino acids, are predicted to be damaging by multiple bioinformatics tools, and were not identified in ethnically matched controls or within variant databases. ELOVL5 encodes an elongase involved in the synthesis of polyunsaturated fatty acids of the ω3 and ω6 series. Arachidonic acid and docosahexaenoic acid, two final products of the enzyme, were reduced in the serum of affected individuals. Immunohistochemistry on control mice and human brain demonstrated high levels in Purkinje cells. In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of SCAs due to mutations in elongase-encoding genes, emphasizing the importance of fatty-acid metabolism in neurological diseases.


[Hygienic characteristics of food hydrolysates made from small ocean fish and krill].
A study was made of the biological value of acid and enzymatic hydrolysates from capelin, luminous anchovy and krill. Hydrolysates were obtained with the use of protosubtilin G-10-X or hydrochloric acid. The products were found to contain 39 to 64% of "crude" protein, with about 40% of total nitrogen belonging to non-protein one, 0.47-2.07% of lipids, 29.7-54.3% of mineral substances including 26.6-52.4% of sodium chloride. All the hydrolysates were limited in tryptophan, the deficiency being more demonstrable in acid hydrolysates. Enzymatic hydrolysate from luminous anchovy was rich in sulfur-containing amino acids (score 112%), whereas the remaining products were marked by their deficiency (score 53-90%). The products were rich in lysine, leucine, isoleucine, and aromatic amino acids. The anabolic efficacy was discovered to be the highest for enzymatic hydrolysate from luminous anchovy, exceeding the analogous characteristics for casein. The biological value of hydrolysate from capelin and krill was lower than that of casein. This was supported by the amino acid analysis data. The assimilability of all hydrolysates was established as fairly high. Hydrolysates are employed for manufacturing broth bricks and pastes.


The Performance of a Mobile Phone Respiratory Rate Counter Compared to the WHO ARI Timer.
To compare the accuracy and efficiency of the respiratory rate (RR) RRate mobile application to the WHO ARI Timer. Volunteers used both devices to measure RR from reference videos of infants and children. Measurements were compared using correlation, Bland-Altman analysis, error metrics and time taken. Measurements with either device were highly correlated to the reference (r = 0.991 and r = 0.982), and to each other (r = 0.973). RRate had a larger bias than the ARI Timer (0.6 vs. 0.04 br/min), but tighter limits of agreement (-4.5 to 3.3 br/min vs. -5.5 to 5.5 br/min). RRate was more accurate than the ARI Timer (percentage error 10.6% vs. 14.8%, root mean square error 2.1 vs. 2.8 br/min and normalized root mean square error 5.6% vs. 7.5%). RRate measurements were 52.7 seconds (95% CI 50.4 s to 54.9 s) faster. During video observations, RRate measured RR quicker with a similar accuracy compared to the ARI Timer.


Comparison of two systems for long-term heart rate variability monitoring in free-living conditions--a pilot study.
A number of small portable systems that can measure HRV are available to address questions related to autonomic regulation in free-living subjects. However, ambulatory HRV measurements obtained through use of these systems have not previously been validated against standard clinical measurements such as Holter recordings. The objective of this study was to validate HRV obtained using a commonly used system, Actiheart, during occupational and leisure-time activities. Full-day ambulatory electrocardiography (ECG) signals were recorded from 8 females simultaneously using Actiheart and Holter recorders, and signals were processed to RR-interval time series. Segments of 5-minute duration were sampled every 30 minutes, and spectral components of the heart rate variability were calculated. Actiheart and Holter values were compared using Deming regression analysis and Bland-Altman plots. In total, 489 segments were available with an HRV value from both Actiheart and Holter recordings after filtering out segments with >10% interpolated beats. No systematic differences between Actiheart and Holter HRV were found. The random deviations between Actiheart and Holter were comparable to the repeatability standard deviation between consecutive Holter measurements. The results show that Actiheart is suited as a stand-alone ambulatory method for heart rate variability monitoring during occupational and leisure-time activities.


Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group.
[corrected] To assess efficacy and safety of gabapentin in the treatment of bipolar disorder. This was a double-blind, placebo-controlled trial of adjunctive gabapentin (dosed flexibly between 900 and 3,600 mg/day). Patients with a lifetime diagnosis of bipolar disorder (type I), and who were currently suffering from symptoms of either mania, hypomania or a mixed state despite ongoing therapy with lithium, valproate, or lithium and valproate in combination were eligible for inclusion. The primary efficacy measures were the baseline to endpoint change in total score on the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAM-D). Both treatment groups had a decrease in total YMRS from baseline to endpoint, but this decrease was significantly greater in the placebo group (-9) than the gabapentin group (-6) (p < 0.05). No difference between treatments was found for the total score on the HAM-D. Secondary efficacy measures were not different between treatment groups. More patients in the placebo group had changes made to their ongoing lithium therapy (n = 12) compared to the gabapentin group (n = 4). When these patients are removed from the efficacy analysis, the YMRS treatment difference still favors placebo, but is no longer statistically significant. Based on gabapentin plasma levels at termination, some patients did not take the study drug as prescribed. The findings of this study did not demonstrate that gabapentin is an effective adjunctive treatment when administered to outpatients with bipolar disorder.


Long-range proton-coupled electron transfer in phenol-Ru(2,2'-bipyrazine)3(2+) dyads.
Two dyads in which either 4-cyanophenol or un-substituted phenol is connected via a p-xylene spacer to a Ru(bpz)3(2+) (bpz = 2,2'-bipyrazine) complex were synthesized and investigated. Selective photo-excitation of Ru(bpz)3(2+) at 532 nm in a CH3CN-H2O mixture leads to the formation of 4-cyanophenolate or phenolate along with Ru(bpz)3(2+) in its electronic ground state. This apparent photoacid behavior can be understood on the basis of a reaction sequence comprised of an initial photoinduced proton-coupled electron transfer (PCET) during which 4-cyanophenol or phenol is oxidized and deprotonated, followed by a thermal electron transfer event in the course of which 4-cyanophenoxyl or phenoxyl is reduced by Ru(bpz)3(+) to 4-cyanophenolate or phenolate. Conceptually, this reaction sequence is identical to a sequence of photoinduced charge-separation and thermal charge-recombination events as observed previously for many electron transfer dyads, with the important difference that the initial photoinduced electron transfer process is proton-coupled. The dyad containing 4-cyanophenol reacts via concerted-proton electron transfer (CPET) whereas the dyad containing un-substituted phenol appears to react predominantly via a stepwise PCET mechanism. Long-range PCET is a key reaction in photosystem II. Understanding the factors that govern the kinetics of long-range PCET is desirable in the broader context of light-to-energy conversion by means of proton-electron separation across natural or artificial membranes.


Old and new stories: revelations from functional analysis of the bovine mammary transcriptome during the lactation cycle.
The cow mammary transcriptome was explored at -30, -15, 1, 15, 30, 60, 120, 240, and 300 d relative to parturition. A total of 6,382 differentially expressed genes (DEG) at a false discovery rate ≤ 0.001 were found throughout lactation. The greatest number of DEG (>3,500 DEG) was observed at 60 and 120 d vs. -30 d with the largest change between consecutive time points observed at -15 vs. 1 d and 120 vs. 240 d. Functional analysis of microarray data was performed using the Dynamic Impact Approach (DIA). The DIA analysis of KEGG pathways uncovered as the most impacted and induced 'Galactose metabolism', 'Glycosylphosphatidylinositol (GPI)-anchor biosynthesis', and 'PPAR signaling'; whereas, 'Antigen processing and presentation' was among the most inhibited. The integrated interpretation of the results suggested an overall increase in metabolism during lactation, particularly synthesis of carbohydrates and lipid. A marked degree of utilization of amino acids as energy source, an increase of protein export, and a decrease of the protein synthesis machinery as well cell cycle also were suggested by the DIA analysis. The DIA analysis of Gene Ontology and other databases uncovered an induction of Golgi apparatus and angiogenesis, and the inhibition of both immune cell activity/migration and chromosome modifications during lactation. All of the highly-impacted and activated functions during lactation were evidently activated at the onset of lactation and inhibited when milk production declined. The overall analysis indicated that the bovine mammary gland relies heavily on a coordinated transcriptional regulation to begin and end lactation. The functional analysis using DIA underscored the importance of genes associated with lactose synthesis, lipid metabolism, protein synthesis, Golgi, transport, cell cycle/death, epigenetic regulation, angiogenesis, and immune function during lactation.


Diclofenac-loaded biopolymeric nanosuspensions for ophthalmic application.
Polymeric nanoparticle suspensions (NS) were prepared from poly(lactide-co-glycolide) and poly(lactide-co-glycolide-leucine) {poly[Lac(Glc-Leu)]} biodegradable polymers and loaded with diclofenac sodium (DS), with the aim of improving the ocular availability of the drug. NS were prepared by emulsion and solvent evaporation technique and characterized on the basis of physicochemical properties, stability, and drug release features. The nanoparticle system showed an interesting size distribution suitable for ophthalmic application. Stability tests (as long as 6 months' storage at 5 degrees C or at 25 degrees C/60% relative humidity) or freeze-drying were carried out to optimize a suitable pharmaceutical preparation. In vitro release tests showed a extended-release profile of DS from the nanoparticles. To verify the absence of irritation toward the ocular structures, blank NS were applied to rabbit eye and a modified Draize test performed. Polymer nanoparticles seemed to be devoid of any irritant effect on cornea, iris, and conjunctiva for as long as 24 hours after application, thus apparently a suitable inert carrier for ophthalmic drug delivery.


Curvature-driven instabilities in thin active shells.
Spontaneous material shape changes, such as swelling, growth or thermal expansion, can be used to trigger dramatic elastic instabilities in thin shells. These instabilities originate in geometric incompatibility between the preferred extrinsic and intrinsic curvature of the shell, which may be modified by active deformations through the thickness and in plane, respectively. Here, we solve the simplest possible model of such instabilities, which assumes the shells are shallow, thin enough to bend but not stretch, and subject to homogeneous preferred curvatures. We consider separately the cases of zero, positive and negative Gauss curvature. We identify two types of supercritical symmetry-breaking instability, in which the shell's principal curvature spontaneously breaks discrete up/down symmetry and continuous planar isotropy. These are then augmented by inversion instabilities, in which the shell jumps subcritically between up/down broken symmetry states and rotation instabilities, in which the curvatures rotate by 90° between states of broken isotropy without release of energy. Each instability has a thickness-independent threshold value for the preferred extrinsic curvature proportional to the square root of Gauss curvature. Finally, we show that the threshold for the isotropy-breaking instability is the same for deep spherical caps, in good agreement with recently published data.


Chiang Mai University Health Worker Study aiming toward a better understanding of noncommunicable disease development in Thailand: methods and description of study population.
Urbanization is considered to be one of the key drivers of noncommunicable diseases (NCDs) in Thailand and other developing countries. These influences, in turn, may affect an individual's behavior and risk of developing NCDs. The Chiang Mai University (CMU) Health Worker Study aims to provide evidence for a better understanding of the development of NCDs and ultimately to apply the evidence toward better prevention, risk modification, and improvement of clinical care for patients with NCDs and NCD-related conditions. A cross-sectional survey of health care workers from CMU Hospital was conducted between January 2013 and June 2013. Questionnaires, interviews, and physical and laboratory examinations were used to assess urban exposure, occupational shift work, risk factors for NCDs, self-reported NCDs, and other NCD-related health conditions. From 5,364 eligible workers, 3,204 participated (59.7%). About 11.1% of the participants had high blood pressure (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) and almost 30% were considered to be obese (body mass index ≥25 kg/m(2)). A total of 2.3% had a high fasting blood glucose level (≥126 mg/dL), and the most common abnormal lipid profile was high low-density lipoprotein (≥160 mg/dL), which was found in 19.2% of participants. The study of health workers offers three potential advantages. The first is that the study of migrants was possible. Socioenvironmental influence on NCD risk factors can be explored, as changes in environmental exposures can be documented. Second, it allows the investigators to control for access to care. Access to care is potentially a key confounder toward understanding the development of NCDs. Lastly, a study of health personnel allows easy access to laboratory investigations and potential for long-term follow-up. This enables ascertainment of a number of clinical outcomes and provides potential for future studies focusing on therapeutic and prognostic issues related to NCDs.


Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: II. Quality of life outcomes submacular surgery trials pilot study report number 2.
To summarize findings from health-related quality-of-life interviews with patients who had recurrent subfoveal choroidal neovascularization secondary to age-related macular degeneration and participated in a randomized pilot trial (focal confluent laser photocoagulation versus submacular surgery) that may assist in planning future assessments of health-related quality of life in patients with age-related macular degeneration. Of 70 patients enrolled in the pilot trial, 54 were interviewed before random assignment to treatment and provided the data analyzed for this report. Patients were scheduled for follow-up interviews at 6, 12, and 24 months after enrollment. The 36-Item Short-Form Health Survey was used in all cases and was administered by an interviewer. The summary scales, Physical Component Summary and Mental Component Summary, were the focus of this analysis. Median Physical Component Summary and Mental Component Summary score at baseline were 47 and 53, respectively. Distributions of scores at baseline and throughout the 2-year follow-up period were similar in the two treatment arms and consistent with those of a sample of the general US population of similar age. Distributions of both Physical Component Summary scores and Mental Component Summary scores for individual patient subgroups at baseline suggested sensitivity to some measures of baseline vision. During 2 years of follow-up interviews, median changes in Physical Component Summary scores were decreases of six points in the laser arm and three points in the surgery arm; in both treatment arms, median change in Mental Component Summary scores was an increase of 2 points. Two-year changes in visual acuity had no discernible effect on Physical Component Summary scores or Mental Component Summary scores; baseline scores were the strongest predictors of 2-year changes in Physical Component Summary and Mental Component Summary scores. Overall, summary scores from the 36-Item Short-Form Health Survey and changes in scores over 2 years in this pilot trial were consistent with the ophthalmic outcome measures (reported elsewhere) that showed no important differences between the treatment arms. These health-related quality-of-life findings provided assurance that the similarity of ophthalmic outcomes in the two treatment arms did not mask changes potentially important to patients that were not captured as part of the clinical outcome data.


The signal averaged P wave in atrioventricular block--evidence for abnormal atrial conduction?
The incidence of atrial fibrillation in patients with atrioventricular block (AVB) appears increased over that for the unpaced population even if atrioventricular synchrony is maintained by dual chamber pacing. To assess whether atrial fibrillation in these patients might be due to concurrent abnormality in atrial activation we performed signal averaged P wave (SAPW) recordings in 15 patients with dual chamber pacemakers implanted for AVB and compared the results to those from 21 unpaced controls. The median (range) age was 69 (53-89) years for patients and 60 (51-78) years for controls. Eleven patients and 12 controls were male. All patients were pacing in VDD mode at the time of study. SAPW recordings were obtained using our previously reported selective P wave averaging system. We measured P wave duration after high pass filtering at 40 Hz, the rate of change of P wave voltage over time (spatial velocity) and low and high frequency spectral energy after Fourier transformation of the P wave signal. We found increased P wave duration, mean spatial velocity and lower frequency energy in patients with AVB compared to controls [duration, 144 (5) vs. 134 (2) ms, p<0.05; mean spatial velocity, 5.6 (0.4) vs. 4.6 (0.1) mV/s, p<0.05; energy 20-150 Hz, 57.4 (8.2) vs. 36.3 (2.8) muV2.s, p<0.01. All values mean (SEM)]. These results suggest that the increased incidence of atrial fibrillation in patients paced for AVB may be related to intrinsic abnormalities of atrial activation and not solely to the pacing mode. Ensuring sequential atrioventricular pacing in these patients may not completely abolish the increased incidence of atrial fibrillation.


Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration.
The hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of upper-motor-neuron degenerative diseases characterized by selective axonal loss in the corticospinal tracts and dorsal columns. Although numerous mechanisms involving defective subcellular transportation, mitochondrial malfunction, and increased oxidative stress have been proposed, the pathogenic basis underlying the neuronal loss is unknown. We have performed linkage analysis to refine the extent of the SPG5 disease locus and conducted sequence analysis of the genes located within this region. This identified sequence alterations in the cytochrome P450-7B1 (CYP7B1) associated with this pure form of HSP. In the liver, CYP7B1 offers an alternative pathway for cholesterol degradation and also provides the primary metabolic route for the modification of dehydroepiandrosterone neurosteroids in the brain. These findings provide the first direct evidence of a pivotal role of altered cholesterol metabolism in the pathogenesis of motor-neuron degenerative disease and identify a potential for therapeutic intervention in this form of HSP.


Quantification of the Elastic Property of Normal Thigh Muscles Using MR Elastography: Our Initial Experience.
This study aimed to apply MR elastography (MRE) to achieve in vivo evaluation of the elastic properties of thigh muscles and validate the feasibility of quantifying the elasticity of normal thigh muscles using MRE. This prospective study included 10 volunteer subjects [mean age, 32.5 years, (range, 23-45 years)] who reported normal activities of daily living and underwent both T2-weighted axial images and MRE of thigh muscles on the same day. A sequence with a motion-encoding gradient was used in the MRE to map the propagating shear waves in the muscle. Elastic properties were quantified as the shear modulus of the following four thigh muscles at rest; the vastus medialis, vastus lateralis, adductor magnus, and biceps femoris. The mean shear modulus was 0.98 ± 0.32 kPa and 1.00 ± 0.33 kPa for the vastus medialis, 1.10 ± 0.46 kPa and 1.07 ± 0.43 kPa for the vastus lateralis, 0.91 ± 0.41 kPa and 0.93 ± 0.47 kPa for the adductor magnus, and 0.99 ± 0.37 kPa and 0.94 ± 0.32 kPa for the biceps femoris, with reader 1 and 2, respectively. No significant difference was observed in the shear modulus based on sex (p < 0.05). Aging consistently showed a statistically significant negative correlation (p < 0.05) with the shear modulus of the thigh muscles, except for the vastus medialis (p = 0.194 for reader 1 and p = 0.355 for reader 2). MRE is a quantitative technique used to measure the elastic properties of individual muscles with excellent inter-observer agreement. Age was consistently significantly negatively correlated with the shear stiffness of muscles, except for the vastus medialis.


pH sensing by intracellular Salmonella induces effector translocation.
Salmonella enterica is an important intracellular bacterial pathogen of humans and animals. It replicates within host-cell vacuoles by delivering virulence (effector) proteins through a vacuolar membrane pore made by the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (T3SS). T3SS assembly follows vacuole acidification, but when bacteria are grown at low pH, effector secretion is negligible. We found that effector secretion was activated at low pH from mutant strains lacking a complex of SPI-2-encoded proteins SsaM, SpiC, and SsaL. Exposure of wild-type bacteria to pH 7.2 after growth at pH 5.0 caused dissociation and degradation of SsaM/SpiC/SsaL complexes and effector secretion. In infected cells, loss of the pH 7.2 signal through acidification of host-cell cytosol prevented complex degradation and effector translocation. Thus, intravacuolar Salmonella senses host cytosolic pH, resulting in the degradation of regulatory complex proteins and effector translocation.


Is intraoperative ultrasonography necessary in laparoscopic partial nephrectomy for exophytic tumours?
The value of IOUS has been proven especially for endophytic kidney tumours, but has not been assessed critically for exophytic kidney tumours. We aimed to evaluate the value of IOUS for exophytic kidney tumours. The data of LPN cases were collected prospectively between 2000 and 2022. Thirty-two of 535 patients who underwent laparoscopic retroperitoneal partial nephrectomy without IOUS were matched with the IOUS applied cases according to tumour size, tumour localization and PADUA score. There were no differences between the two groups in terms of the matching parameters. The average warm ischemia time was 14 min for the IOUS group (range 9-32 min) and 20 min for the non-IOUS group (range 7-52 min) (p = 0.01). Also, the average cutting time was shorter in the IOUS group (6 min vs 9 min) (p = 0.046). There was no difference between the two groups in terms of suturing times (8 min vs 8.5 min) (p = 0.66). The average tumour size was 3.5 cm and pathologically-proven residual tumour was detected in one patient in each group. The use of IOUS in laparoscopic retroperitoneal partial nephrectomy for exophytic kidney tumours may shorten the warm ischemia time by reducing the cutting time.


Children's secure base script knowledge as a mediator between early life stress and later behavior problems.
Attachment theory posits that children's interactions with caregivers contribute to internalized representations that reflects the common and recurring elements of sensitive caregiving interactions (i.e. the secure base script). These internalized representations are theorized to influence later adaptation, including the development of psychopathology. Given prior research suggesting that stress exposure may undermine secure base script knowledge (SBSK), this study evaluated SBSK development in early childhood as a mechanism by which childhood stress exposure may influence later adaptation. We hypothesized that children's (N = 230; Mage = 73.30 months, SD = 2.51, 50% girls; 45.7% Latinx) stress exposure would be associated with lower levels of SBSK at age 6, which, in turn, would contribute to increased internalizing and externalizing symptoms at age 8. SBSK emerged as a significant mechanism by which early life stress may contribute to later externalizing, but not internalizing, child behavior problems. These findings highlight the role of SBSK as a profitable focus for both risk identification and intervention efforts aimed at reducing behavioral maladaptation among stress-exposed children.


Increasing the Uptake of HIV Testing among Men in Tanzania: A Novel Intervention for Bar Patrons.
We investigated a novel community-based HIV testing and counseling (HTC) strategy by recruiting men from bars in northern Tanzania in order to identify new HIV infections. All bars in the town of Boma Ng'ombe were identified and male patrons were systematically invited to participate in a health study. HIV testing was offered to all enrolled participants. Outputs included HIV test yield, cost per diagnosis, and comparison of our observed test yield to that among male patients contemporaneously tested at five local facility-based HTC. We enrolled 366 participants and identified 17 new infections - providing a test yield of 5.3% (95% Confidence interval [CI] 3.3-8.4). The test yield among men contemporaneously tested at five local HTC centers was 2.1% (95% CI 1.6-2.8). The cost-per-diagnosis was $634. Our results suggest that recruiting male bar patrons for HIV testing is efficient for identifying new HIV infections. The scalability of this intervention warrants further evaluation.


International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.
There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.


Comparison of social structures within cities of very different sizes.
People make a city, making each city as unique as the combination of its inhabitants. However, some cities are similar and some cities are inimitable. We examine the social structure of 10 different cities using Twitter data. Each city is decomposed to its communities. We show that in many cases one city can be thought of as an amalgamation of communities from another city. For example, we find the social network of Manchester is very similar to the social network of a virtual city of the same size, where the virtual city is composed of communities from the Bristol network. However, we cannot create Bristol from Manchester since Bristol contains communities with a social structure that are not present in Manchester. Some cities, such as Leeds, are outliers. That is, Leeds contains a particularly wide range of communities, meaning we cannot build a similar city from communities outside of Leeds. Comparing communities from different cities, and building virtual cities that are comparable to real cities, is a novel approach to understand social networks. This has implications when using social media to inform or advise residents of a city.


Single radial hemolysis test for rubella immunity and recent infection.
The single radial hemolysis (SRH) test was compared with the hemagglutination inhibition (HI) test for establishing rubella immune status and diagnosing recent infection. Correlation between mean SRH diameters and HI titers greater than or equal to 1:8 was high (R = 0.99). It is suggested that a level of greater than or equal to 5 IU represents low-level antibody and that greater than or equal to 15 IU is a conservative threshold for designation of immunity. Of 343 sera tested, only 1 false-positive was found by SRH with the 5 IU cutoff level. The SRH test could detect serum antibody levels as low as 2.5 IU, whereas 15 IU was generally the limit of resolution of the HI test. Data from sucrose density gradient fractionation of serum demonstrated that neither rubella-specific immunoglobulin M (IgM) nor early postinfection HI-reactive IgG was detected by SRH. However, diagnostic changes in antibody titer measured by SRH were in general greater than those measured by HI. The SRH test showed diagnostic titer changes in some sera containing specific IgM for which no such changes were detected by the HI test. A 2.5-mm difference in hemolytic zone diameters (a fourfold rise in international units) between acute- and convalescent-phase serum pairs was chosen as being of diagnostic significance. This difference was less than the minimum observed difference of 2.9 mm from 59 serum pairs showing diagnostic changes by HI and far exceeded (greater than 3.6 standard deviations) the within-test and individual variability seen for 95 pregnant women from whom samples were obtained during each trimester.


[Features of epithelial-bacterial interactions in bacterial vaginosis].
Study of features of interactions of mucosal epitheliocytes of vagina with dominant and associative vaginal microsymbionts in bacterial vaginosis. Changes in growth characteristics and ability to form biofilms of Staphylococcus aureus, Escherichia coli, Lactobacillus spp. under the influence of secretory products of vaginal epitheliocytes obtained from 36 women with bacterial vaginosis and 32 practically healthy women were studied. Vaginal epitheliocytes of women with bacterial vaginosis were shown to change their functional activity during contact with microorganisms and their secretory products, causing differential influence on the properties of symbiont bacteria. A suppression of growth of dominant microsymbionts--lactobacilli, mostly their peroxide producing biovars, and a weakening of suppressing effect on the growth of biomass of associative microorganisms accompanied by stimulation of their ability to form biofilms was noted. Preliminary contact of an epitheliocyte with bacterial cell or its supernatant increased the intensity of the changes of properties of bacteria under the influence of secretory products of epitheliocytes. Suppression of growth of lactobacilli (mostly their peroxide producing biovars) and stimulation of the ability to for biofilms of the associative microorganisms as a result of bacterial-epithelial interactions in bacterial vaginosis determine mechanisms of formation and stability of pathomicrobiocenosis and a reduction of colonization resistance of vaginal biotope.


In vivo imaging of astrocytosis in Alzheimer's disease: an ¹¹C-L-deuteriodeprenyl and PIB PET study.
Astrocytosis is an important feature of the neuropathology of Alzheimer's disease (AD), yet there is currently no way of detecting this phenomenon in vivo. In this study we examine the retention of the positron emission tomography (PET) tracer (11)C-L-deuteriodeprenyl (DED), thought to bind activated astrocytes, in 9 patients with moderate to severe AD compared with 11 healthy controls. As a measure of amyloid load, (11)C-labelled Pittsburgh Compound B (PIB) retention was determined. Results show a significantly higher (11)C-L-DED retention in the frontal (35.1% increase, p = 0.001), parietal (35.2%, p = 0.001), temporal (30.9%, p = 0.0001) and medial temporal lobes (22.3%, p = 0.001) in AD compared to healthy controls after blood flow correction. DED retention in the sensorimotor and occipital cortices, and in white matter and subcortical structures, did not differ between groups. There was a moderate but statistically significant (r = 0.492, p = 0.01) correlation between DED and PIB retention values. Our conclusion is that DED may serve as an in vivo marker for astrocytosis in AD, providing a window into intermediate processes between amyloidosis and neuronal loss and a means of monitoring immunotherapy.


Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg combination treatment in patients with persistent asthma previously receiving medium-dose inhaled corticosteroids.
Asthma is a heterogeneous condition characterized by reduced lung function, chronic inflammation, and periodic asthma deteriorations. This study was performed to evaluate the effect of mometasone furoate (MF)/formoterol (F) combination, 200/10 microg, administered twice daily (b.i.d.) on asthma deteriorations and pulmonary function in patients with asthma uncontrolled on medium-dose inhaled corticosteroid (ICS). After 2- to 3-week open-label run-in with MF 200 microg b.i.d., patients (>or=12 years) were randomized to 26 weeks of treatment with MF/F 200/10 microg, MF 200 microg, F 10 microg, or placebo b.i.d. Coprimary end points were time to first asthma deterioration (MF/F versus F) and bronchodilation, assessed by the area under the curve of the change in forced expiratory volume in 1 second 0-12 hours (FEV(1) AUC(0-12h); MF/F versus MF). A total of 781 patients were randomized. Treatment with MF/F 200/10 microg reduced asthma deteriorations and clinically judged deteriorations (i.e., deterioration resulting in emergency treatment, hospitalization, or treatment with additional excluded asthma medication [i.e., systemic corticosteroids]). The proportion of patients experiencing asthma deteriorations was MF/F, 30.4%; MF, 33.9%; F, 54.0%; placebo, 55.6% (p < 0.001, MF/F versus F and placebo). There was a sixfold reduction in clinically judged deteriorations with MF/F versus F and placebo (p < 0.001). Lung function improved more rapidly with MF/F than MF and placebo. Mean change from baseline FEV(1) AUC(0-12h) at week 12 was MF/F, 11.7% versus MF, 5.7%; F, 8.5%; and placebo, 3.9% (p < 0.001). Treatment-related AEs were rare and similar across groups. Treatment with MF/F 200/10 microg was effective in reducing the risk of asthma deteriorations. MF/F was safe and provided rapid and sustained bronchodilation in patients with asthma.


Multimodal Speaker Diarization.
We present a novel probabilistic framework that fuses information coming from the audio and video modality to perform speaker diarization. The proposed framework is a Dynamic Bayesian Network (DBN) that is an extension of a factorial Hidden Markov Model (fHMM) and models the people appearing in an audiovisual recording as multimodal entities that generate observations in the audio stream, the video stream, and the joint audiovisual space. The framework is very robust to different contexts, makes no assumptions about the location of the recording equipment, and does not require labeled training data as it acquires the model parameters using the Expectation Maximization (EM) algorithm. We apply the proposed model to two meeting videos and a news broadcast video, all of which come from publicly available data sets. The results acquired in speaker diarization are in favor of the proposed multimodal framework, which outperforms the single modality analysis results and improves over the state-of-the-art audio-based speaker diarization.


Prevalence of Borrelia burgdorferi infection in a series of 98 primary cutaneous lymphomas.
Borrelia burgdorferi has been variably associated with different forms of primary cutaneous lymphoma. Differences in prevalence rates among reported studies could be a result of geographic variability or heterogeneity in the molecular approaches that have been employed. In the present study, we investigated the prevalence of Borrelia burgdorferi sensu lato DNA in diagnostic tissue samples from fresh cutaneous biopsies of 98 primary cutaneous lymphomas and 19 normal skin controls. Three different polymerase chain reaction (PCR) protocols targeting the hbb, flagellin, and Osp-A genes were used. Direct sequencing of both sense and antisense strands of purified PCR products confirmed the specificity of the amplified fragments. Sequence specificity was assessed using the Basic Local Alignment Search Tool, and MultAlin software was used to investigate the heterogeneity of target gene sequences across the different samples. Borrelia DNA was not detected in 19 controls, 23 cases of follicular lymphoma, 31 cases of extranodal marginal zone lymphoma, or 30 cases of mycosis fungoides. A single case of 14 diffuse large B-cell lymphoma cases was positive for B. burgdorferi. This study does not support a pathogenic role of B. burgdorferi in primary cutaneous B- and T-cell lymphomas from areas nonendemic for this microorganism and the consequent rationale for the adoption of antibiotic therapy in these patients.


Morphologically normal spermatozoa of patients with secretory oligo-astheno-teratozoospermia have an increased aneuploidy rate.
Normal morphology is a major criterion for selecting spermatozoa to be injected. Given that teratozoospermia is one of the most critical parameters associated with sperm aneuploidy, the purpose of this study was to evaluate the aneuploidy rate of morphologically normal spermatozoa of patients with oligo-astheno-teratozoospermia (OAT). Ten patients with secretory OAT and six age-matched normozoospermic men with a normal karyotype were enrolled. After assignment to normal or abnormal category, the location of each spermatozoon was recorded using an electronic microstage locator. Slides were then subjected to triple-colour fluorescence in situ hybridization for chromosomes X, Y and 12. OAT patients had a lower number of morphologically normal and abnormal spermatozoa carrying the X chromosome, compared with normozoospermic men. They also exhibited increased XY and XX disomy rates. Morphologically abnormal spermatozoa from normozoospermic men also had an increased XX disomy rate compared with normally shaped spermatozoa obtained from the same men. The total sperm aneuploidy rate of morphologically abnormal spermatozoa of normozoospermic men was 4.4-fold higher than that of spermatozoa with normal morphology. The total aneuploidy rates of spermatozoa with normal or abnormal head shape from OAT patients were similar to each other and to that of abnormally shaped spermatozoa from normozoospermic men, but they were higher than the rate found in normally shaped spermatozoa of normal men. Normally shaped spermatozoa of OAT patients have an increased aneuploidy rate.


Let's Talk About Those Herbs You Are Taking: Ethical Considerations for Communication With Patients With Cancer About Complementary and Alternative Medicine.
Oncologists face ethical challenges when patients use potentially harmful complementary and alternative medicine in addition to or instead of conventional treatments for their cancer. For example, a patient may forego effective cancer treatment in favor of alternative therapies and suffer significant harm as a result. Similarly, false beliefs about the efficacy of complementary therapies may complicate the process of shared decision making about cancer treatment. In this vignette, we discuss clinicians' obligations and provide recommendations for ethically sound communication practices in this clinical context.


A de novo nonsense mutation in ZBTB18 plus a de novo 15q13.3 microdeletion in a 6-year-old female.
ZBTB18 has been proposed as candidate gene for microcephaly and abnormalities of the corpus callosum based on overlapping microdeletions of 1q43q44. More recently, de novo mutations of ZBTB18 have been identified in patients with syndromic and non-syndromic intellectual disability. Heterozygous microdeletions of 15q13.3 encompassing the candidate gene CHRNA7 are associated with developmental delay or intellectual disability with speech problems, hypotonia, and seizures. They are characterized by significant variability and reduced penetrance. We report on a patient with a de novo ZBTB18 nonsense mutation and a de novo 15q13.3 microdeletion, both in a heterozygous state, identified by next generation sequencing and array-CGH. The 6-year-old girl showed global developmental delay, absent speech, therapy-refractory seizures, ataxia, muscular hypotonia, and discrete facial dysmorphisms. Almost all of these features have been reported for both genetic aberrations, but the severity could hardly been explained by the microdeletion 15q13.3 alone. We assume an additive effect of haploinsufficiency of ZBTB18 and CHRNA7 in our patient. Assembling the features of our patient and the published patients, we noted that only one of them showed mild anomalies of the corpus callosum. Moreover, we hypothesize that nonsense mutations of ZBTB18 are associated with a more severe phenotype than missense mutations. This report indicates that haploinsufficiency of additional genes beside ZBTB18 causes the high frequency of corpus callosum anomalies in patients with microdeletions of 1q43q44 and underlines the importance of an NGS-based molecular diagnostic in complex phenotypes.


Rapid Diagnosis of Mycobacterium genavense Disseminated Infection by the Microseq 500: A Case Report in A Two Year Old HIV-Negative Child.
This paper evaluates the capability of MicroSeq 500 instrument to improve the diagnosis of Mycobacterium genavense The strain was isolated from a two year old child admitted to our hospital for hepatosplenomegaly and massive abdominal lymphadenopathies. DNA was extracted from a lymph node and examined by amplifying 500 bp at the 5' end of 16S rRNA gene using MicroSeq 500 16S rDNA Bacterial Identification PCR kit. Sequencing reactions were performed with MicroSeq 500 16S rDNA Bacterial Identification Sequencing kit (Applied Biosystems, USA). Afterwards, sequences were analyzed by GenBank database and identified as Mycobacterium genavense, a slow-growing nontuberculous mycobacterium. The use of 16S rRNA gene sequencing for the identification of bacteria allows the recognition of new clinically relevant agents, eliminating the culture result waiting times.


Isolated cardiac valve involvement in smoldering adult T-cell leukemia/lymphoma.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by infection with the Human T-cell Lymphotropic Virus Type 1 (HTLV-1). Cardiac involvement in patients with ATLL is infrequent, and when it happens it is usually seen in aggressive ATLL subtypes. However, ATLL presenting as isolated cardiac valve involvement is extremely rare. To date, only three histologically proven cases of ATLL with isolated cardiac valve involvement have been reported. Herein, we describe a 61-year-old Peruvian man who presented heart failure symptoms secondary to progressive cardiac valve infiltration. The patient underwent mitral valve replacement with a mechanical prosthesis. Histopathological evaluation of the resected valve revealed leaflet thickening with a nodular appearance due to fibrous tissue containing atypical T-lymphocytes with Foxp3 expression, infiltrating all layers of the resected valve. Interestingly, tumor cells were distributed around an incidental venous malformation (i.e., cavernous hemangioma). Postoperative evaluation demonstrated positive serology for HTLV-1, and a diagnosis of ATLL was established. Postoperative positron emission tomography/computed tomography did not show lesions outside the heart and cell blood counts were within normal range with low level of circulating CD4+ CD25+ lymphoma cell counts (7%); therefore, patient's disease was considered as smoldering ATLL and a "watch and wait" strategy was pursued. Currently, the patient is alive with no progression of disease after 18 months from diagnosis. Isolated cardiac valve involvement by ATLL should be considered in the differential diagnosis of HTLV-1 carriers with progressive heart failure, even when systemic lymphoma involvement is absent or not apparent.


An Androgenetic Alopecia Remedy Based on Marine Collagen Peptide-Incorporated Dissolving Microneedles.
Given that current androgenetic alopecia (AGA) medications have adverse effects such as sexual dysfunction and drug dependence, researchers are actively exploring natural bioactive ingredients and innovative approaches (e.g., transdermal drug delivery systems) to effectively combat hair loss with minimal side effects. Herein, we develop a new transdermal drug delivery system incorporating globefish skin collagen peptides with dissolving microneedles (GSCPs-MNs) for hair regrowth. These microneedles generate skin micro-wounds upon application, which not only improves the efficiency of bioactive ingredients delivery, but also stimulates signals involved in hair follicle (HF) regeneration. Our in vivo study shows that minimally invasive implanted GSCPs-MNs are more effective than topical GSCPs in reducing inflammation and promoting collagen formation. Additionally, the upregulation of vascular markers including VEGF and CD31 alongside the downregulation of TNF-α, IL-1β, and malondialdehyde (MDA) index indicate that GSCPs-MNs can significantly alleviate inflammation and oxidation, as well as promoting vascularization and HF functionalization. Overall, our findings suggest that GSCPs-MNs can effectively promote hair regrowth in AGA mice, which offer excellent prospects for the development of new therapeutics and cosmetic supplements for hair loss, along with the combined drug delivery optimization, which could alleviate hair loss in patients with AGA.


Encephalopathy associated with enteroinvasive Escherichia coli 0144:NM infection.
Central nervous system manifestations typically occur with Shigella gastroenteritis and also in enteric Salmonella and Campylobacter infections. To date no association between enteroinvasive Escherichia coli infection and neurologic symptoms has been described. Two children with diarrhea caused by E. coli 0144:NM had otherwise unexplained encephalopathy manifested by profound stupor in one child and by obtundation and meningismus in the other one. These cases of infection occurred in northern Israel during a period of an unusually high rate of enteric infection caused by this organism. None of the microbiologic properties studied were uniquely attributable to the encephalopathic cases. The two encephalopathic as well as all eight nonencephalopathic isolates studied possessed the 140-MDa invasive plasmid. All 10 isolates examined produced small amounts of cytotoxin by the HeLa cell assay, all were nonmotile, and all had identical antibiograms. Eight of 10 of the isolates had identical plasmid profiles, while 2 isolates (from nonencephalopathic patients) had slightly different plasmid profiles. This is the first report of encephalopathy associated with enteroinvasive E. coli.


Neuroprotective Activity of Polyphenol-Rich Ribes diacanthum Pall against Oxidative Stress in Glutamate-Stimulated HT-22 Cells and a Scopolamine-Induced Amnesia Animal Model.
Ribes diacanthum Pall, a native Mongolian medicinal plant, has been reported to show antioxidant activities due to its polyphenol and flavonoid content, and is especially rich in the ethyl acetate fraction from an 80% methanol extraction (RDP). We assessed the cytoprotective effect of RDP on glutamate-caused oxidative stress and apoptosis in mouse hippocampal neuronal cells (HT-22 cells). Cell viability was significantly recovered by RDP treatment. Also, RDP effectively decreased the glutamate-induced production of intracellular reactive oxygen species (ROS). In flow cytometric analysis, apoptotic cells and the mitochondrial membrane potential were suppressed by RDP. In the Western blotting analysis, we found that RDP not only decreased the release of apoptotic proteins but also recovered anti-apoptotic protein. Additionally, RDP enhanced the antioxidant defense system by regulating the expression of antioxidant enzymes. Furthermore, treatment with RDP activated the BDNF/TrkB pathway. In accordance with the in vitro results, RDP meliorated memory deficit by defending hippocampal neuronal cells against oxidative damage in scopolamine-injected mice. Taken together, our present study showed that RDP exerted antioxidant and neuroprotective actions against oxidative stress. Therefore, RDP might facilitate the development of candidates for functional health foods for neurodegenerative disorders.


Prevalence of obesity and ischaemic heart disease in hypertensive subjects.
In the present study the prevalence of obesity and its association with ischemic heart disease, recognized according to clinical criteria (chest pain or previous infarction) and/or instrumental data, were described in 8,847 normotensive subjects and in 867 hypertensive subjects, hospitalized during a ten years period (1983-1992), through a cross-sectional study. In view of this all the subjects were considered as lean or obese according to their body mass index (BMI) and to sex specific cut-off values reported in the Italian Consensus Conference on Obesity. In particular, according to BMI values, the subjects were grouped as lean, overweight, moderate and severe obese subjects. Our results indicated that 3,982 normotensive subjects (45%) could be considered lean, whereas 2,654 of them (30%) were overweight, 1,769 of them (20%) were moderate obese and 442 of them (5%) were severe obese. On the contrary only 206 hypertensives (23.7%) might be considered lean, whereas 313 (36.1%) were overweight, 302 (34.8%) were moderate obese and 46 (5.3%) were severe obese. According to age subgrouping (lower than or equal to 65 years or higher than 65 years) the distribution of hypertensives within the lean, overweight, moderate and severe obese groups did not change significantly, but, according to sex subgrouping, the distribution of hypertensives within the BMI groups was significantly different (chi 2, p < 0.001). When we considered the degree of hypertension, distribution of hypertensives was significantly different according to c2 test (p < 0.004), suggesting that the percentage of the subjects with severe hypertension increased only in subjects with severe obesity. Concomitant ischaemic heart disease (IHD) was also documented in 350 normotensives (4%) and in 119 hypertensives (13.8%). The prevalence of IHD was not significantly different in lean, overweight, moderate and severe obese hypertensives, also when sex and smoking habits were considered. Our data indicated a strong association between obesity and hypertension. In addition they may be consistent with the suggestion that obese hypertensives were not characterized by a lower risk of ischaemic heart disease (IHD), than lean hypertensives.


Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models.
Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.


Evaluating SARS-CoV-2 Seroconversion Following Relieve of Confinement Measures.
Seroprevalence studies are crucial both for estimating the prevalence of SARS-CoV-2 exposure and to provide a measure for the efficiency of the confinement measures. Portuguese universities were closed on March 16th 2020, when Portugal only registered 62 SARS-CoV-2 infection cases per million. We have validated a SARS-CoV-2 ELISA assay to a stabilized full-length spike protein using 216 pre-pandemic and 19 molecularly diagnosed SARS-CoV-2 positive individual's samples. At NOVA University of Lisbon, presential work was partially resumed on May 25th with staggered schedules. From June 15th to 30th, 3-4 weeks after the easing of confinement measures, we screened 1,636 collaborators of NOVA university of Lisbon for the presence of SARS-CoV-2 spike specific IgA and IgG antibodies. We found that spike-specific IgG in 50 of 1,636 participants (3.0%), none of which had anti-spike IgA antibodies. As participants self-reported as asymptomatic or paucisymptomatic, our study also provides a measurement of the prevalence of asymptomatic/paucisymptomatic SARS-CoV-2 infections. Our study suggests that essential workers have a 2-fold increase in viral exposure, when compared to non-essential workers that observed confinement. Additional serological surveys in different population subgroups will paint a broader picture of the effect of the confinement measures in the broader community.


Dietary fat during pregnancy and lactation increases milk fat and insulin-like growth factor I concentrations and improves neonatal growth rates in swine.
Primiparous (n = 24) and multiparous (n = 24) sows were used to examine the effects of supplemental dietary fat and induction of parturition (d 112) on colostrum and milk composition and suckling piglet growth. Sows were assigned to one of eight treatments on d 90 of gestation that included variables such as parity (1 vs. >/=3), dietary fat (0 vs. 10%), and farrowing (natural vs. induction via lutalyse on d 112). Piglets suckling fat-supplemented dams grew up to 25% faster than control pigs nursing unsupplemented sows (250 vs. 200 g/d; P < 0.01). Improved growth was correlated with elevated milk fat and insulin-like growth factor (IGF) concentrations associated with fat supplementation. Dietary fat elevated milk fat concentration at 48 and 72 h postfarrowing by 21.6 and 22.6%, respectively (P < 0.05). Compared with nonfat-fed controls, multiparous sows fed 10% fat showed a more consistent rise in milk fat concentration, with 26% and 41% elevations for induced or naturally farrowing sows, respectively, vs. a 19% reduction or a 1% elevation in induced or naturally farrowing gilts (P < 0.01). The concentration of milk IGF-I tended to be lower in gilts than in multiparous sows (P < 0.2, 95.7 vs. 117.4 microg/L), and levels were particularly low in milk from induced gilts receiving no additional dietary fat (44.7 microg/L). However, fat supplementation elevated IGF-I to levels (110.6 microg/L) exceeding those measured in unsupplemented, naturally farrowing control sows and gilts (95.8 microg/L). In conclusion, supplemental dietary fat elevates milk fat in multiparous sows more than primiparous gilts regardless of farrowing treatment (induced vs. natural farrowing) and improves piglet growth throughout lactation irrespective of parity or farrowing treatment. The potential of supplemental dietary fat to reverse the reductions in milk IGF-I observed in first-parity females and in dams induced to farrow merits further investigation.


Economic and herbicide use impacts of glyphosate-resistant crops.
More than 95% of United States maize, cotton, soybean and sugarbeet acres are treated with herbicides for weed control. These products are used to improve the economic profitability of crop production for farmers. Since their introduction in 1996, over 75 million acres of genetically engineered glyphosate-resistant crops have been planted, making up 80% of soybean acres and 70% of cotton acres in the USA. These genetically engineered crops have been adopted by farmers because they are perceived to offer greater economic benefits than conventional crop and herbicide programs. The adoption of glyphosate-resistant crops has saved US farmers 1.2 billion dollars associated with the costs of conventional herbicide purchases, application, tillage and hand weeding. With the adoption of glyphosate-resistant sugarbeets on currently planted sugarbeet acres, US growers could potentially save an additional 93 million dollars. The adoption of glyphosate-resistant crops by US agriculture has reduced herbicide use by 37.5 million lbs, although the adoption of glyphosate-resistant sugarbeets would dampen this reduction by 1 million lbs.


Impact of breast reconstruction on the decision to undergo contralateral prophylactic mastectomy.
In the last decade, there has been increasing use of contralateral prophylactic mastectomy (CPM) in patients with unilateral breast cancer and ductal carcinoma-in-situ (DCIS) undergoing mastectomy. Although many factors have been proposed to explain this trend, the impact of breast reconstruction on CPM has not been studied. A retrospective review of patients with unilateral invasive breast cancer or DCIS from Surveillance, Epidemiology, and End Results registry data (2004-2008) was conducted. Characteristics of patients undergoing CPM and reconstruction were evaluated. A total of 102,674 patients diagnosed with DCIS or stage I to III infiltrating breast cancer underwent mastectomy for their primary lesion. Of these, 16,197 patients (16 %) underwent a CPM. A significantly higher proportion of women undergoing CPM had reconstruction performed (46 %) than those patients not undergoing CPM (15 %) (p < 0.001). Of the 20,760 patients (20 %) who underwent reconstruction, 7410 (36 %) had implant reconstruction, 7705 (37 %) tissue reconstruction, and 1941 (9 %) combined tissue/implant reconstruction; there were no data for 3,702 (18 %). There was an increasing trend of patients undergoing reconstruction from 2004 (n = 3390, 16.3 %) to 2008 (n = 5406, 26 %) (p < 0.001). On multivariable analysis, significant variables predicting CPM included age <45 years, stage I disease (odds ratio [OR] 1.44, 95 % confidence interval [CI] 1.35-1.54), lobular histology (OR 1.15, 95 % CI 1.11-1.20), and undergoing breast reconstruction (OR 3.58, 95 % CI 3.41-3.75). Besides age, undergoing reconstructive surgery is the factor most strongly associated with CPM. This suggests that apart from risk reduction, the availability of and/or patient willingness to undergo breast reconstruction may influence the decision to undergo CPM.


[Characteristics of the course of recurrent-progressive schizophrenia with the dysmorphomania syndrome].
As many as 60 patients suffering from dysmorphomania were examined. The patients' age ranged from 17 to 61 years at the moment of examination. Analysis of the disease course has demonstrated that all the patients suffered from attack-like progredient schizophrenia. Depending on the structure of the attacks and dynamics of dysmorphomania two clinical groups were distinguished. In group I, the disease picture was specified by mainly affective attacks; dysmorphomania occurred at the adolescent (more rarely at the juvenile) age. It was characterized by a tendency towards complication, with a progressive deactualization in repeated attacks of the disease. In group II, the disease manifested itself by complication of the attacks which progressed from affective ones to the states of depression with interpretive paranoid or (and) affective-paranoid attacks. The syndrome of dysmorphomania occurred at varying age and was marked by diversity of manifestations, complication in the attacks that followed (fabula expansion, formation of hypochondriac delirium coinciding with dysmorphomania in the subject matter). The given group was characterized by progredient course of schizophrenia.