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ABSTRACT The minimum inhibitory concentration (MIC) of echinocandins against Aspergillus spp. does not represent the actual inhibition threshold of echinocandins. Therefore, the recommended method to evaluate their activity is determining the minimum effective concentration (MEC) in broth microdilution, a method that is less common in clinical settings. This study aimed to assess a user-friendly commercial method, Sensititre YeastOne (SYO), to determine the effectiveness of echinocandins (caspofungin, anidulafungin and micafungin) against Aspergillus spp. Echinocandins MEC was determined against 23 isolates of Aspergillus spp. using SYO and the reference Clinical and Laboratory Standards Institute (CLSI) method. MECs were read with an inverted microscope and a reading mirror. Essential agreement (EA) between the tested methods was defined as a ±twofold dilution difference. There was a high EA (91%–100%) between the reference method and SYO in determining echinocandins MEC against Aspergillus isolates using inverted microscopy. A high EA was also observed between SYO MEC determined by inverted microscopy and a reading mirror, but different incubation times were required. SYO is a reliable, simple method for determining the MEC of echinocandins against Aspergillus isolates, preferably with an inverted microscope, and can be easily used in clinical laboratories when echinocandin susceptibility testing is required.IMPORTANCEUsing a commercial method such as Sensititre YeastOne (SYO) to determine the minimum effective concentration (MEC) of echinocandins against Aspergillus spp. has been shown to be a reliable alternative to the Clinical and Laboratory Standards Institute (CLSI) reference method. This makes it more suitable for high-volume clinical laboratories. SYO provides accurate results comparable to the standard method and could potentially improve patient care by guiding more optimal antifungal treatment choices for patients with Aspergillus infections.

Abstract Objective This study aimed to assess weight gain associated with treatment switching to INSTI-based regimens in people living with HIV (PLWH) and to determine whether it is accompanied by worsening features of hypertension, dyslipidemia, or hyperglycemia. Methods In this two-center retrospective observational study, we assessed weight gain and metabolic features in PLWH who switched to an INSTI-based regimen (study group) as compared to patients who remained on a non-INSTI regimen (control group) over a 24-month follow-up period. Results One-hundred seventy-four PLWH were included in the study group, and 175 were included in the control group. The study group gained 2.51 kg ± 0.31 (mean ± standard deviation) over the 2 years of follow-up, while the control group gained 1.1 ± 0.31 kg over the same time course (p

Concerns have been mounting regarding the underdiagnosis of HIV among respiratory co-infections associated with the COVID-19 pandemic. The delay in recognizing HIV/AIDS may be attributed to the similarities in clinical, laboratory (lymphopenia) and imaging presentations, which are typical for advanced AIDS but could also be indicative of a COVID-19 infection.Herein, we present a case of a 38-year-old ultraorthodox Jew with a late diagnosis of AIDS in the context of COVID-19 infection. This occurred after several months of recurrent respiratory infections compounded by SARS-COV 2 infection, during which no HIV testing was conducted. As a result, a cascade of various opportunistic infections ensued, leading to an extended hospitalization period, ultimately culminating in the patient's demise despite receiving optimal treatment.

Microbiome composition is influenced by genetics, although the specific host genetic factors responsible are not well known. Here, the authors performed a genome-wide meta-analysis to discover host genetic effects on skin microbiota and finding potential causal effects of microbiota composition on skin diseases.

Despite the progress in contemporary antiretroviral therapy (ART) and the continuous changes in treatment guidelines, virological failure (VF) is still an ongoing concern. The goal of this study was to assess factors related to VF after first-line ART. A longitudinal cohort retrospective study of individuals on first-line ART diagnosed with HIV-1 in 2010–2018 and followed-up for a median of two years was conducted. Demographics, baseline and longitudinal CD4 counts, treatment regimens, adherence and VF were recorded. The Cox proportional hazards regression and mixed models were used. A cohort of 1130 patients were included. Overall, 80% were males and 62% were Israeli-born individuals. Compared to individuals diagnosed in 2010–2014, when treatment was initiated according to CD4 levels, those diagnosed in 2015–2018 were older and had lower baseline CD4 counts. VF was recorded in 66 (5.8%) patients. Diagnosis with CD4 p < 0.001) and non-integrase strand transfer inhibitor regimens (non-INSTI, HR = 1.80, 95%CI:1.01–3.24, p = 0.047) increased VF risk. No impact of baseline resistance was observed. We concluded that the early detection of HIV-1 infection and usage of INSTI-based regimens are recommended to reduce VF.

Several small studies have indicated that daily emollient use from birth might delay, suppress or prevent atopic dermatitis (AD). Two larger trials did not confirm this; however, a recent smaller study indicated a protective effect if daily emollient use is used in the first 2 months of life. Further research is needed to evaluate the effect of emollient use on development of AD. The current study randomly assigned 50 newborns who were at high risk of developing AD (1:1) to receive general infant skin-care advice (control group), or skin-care advice plus emollient with advice to apply emollient at least once daily until 1 year of age (intervention group). Repeated skin examinations, skin physiology measurements and skin microbiome profiling were performed. Of the children in the intervention and control groups, 28% and 24%, respectively, developed AD (adjusted Relative Risk (RR) 1.19, p = 0.65, adjusted risk difference 0.05). Skin pH decreased and transepidermal water loss and stratum corneum hydration increased over time in both groups with no significant differences. In the intervention group skin microbiome alpha diversity increased earlier, and the abundance of Streptococcus and Staphylococcus species were significantly reduced at month 1. Daily early emollient use in children with high risk of AD was safe, but it did not significantly reduce the risk of developing AD or impact skin physiology development.

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.

Abstract Background After decades of constant increase in HIV diagnoses among men who have sex with men (MSM), a gradual decrease has been reported in recent years. Timely detection of HIV leads to early treatment and behavioral changes which decrease further transmissions. This cross-sectional study aimed to assess demographic and behavioral characteristics of individuals who were tested for HIV in Jerusalem, Israel. Methods This study compared individuals who were tested at Hadassah AIDS Center (HAC) with those tested at the Jerusalem Open House (JOH) - an LGBTQ community center. Participants completed anonymous questionnaires regarding their demographic, HIV-testing history, and sexual behaviors. High-risk sexual behavior (HRSB) was defined as a diagnosis of sexually transmitted disease or condomless anal/vaginal sex during the last year. Results Among 863 participants, 104 (12.1%) were tested in HAC and 759 (87.9%) in JOH. Of those, 19 (18.3%) and 227 (29.9%) were HRSB, respectively. Two MSM were tested positive in JOH. JOH received more MSM, HRSB and individuals who were previously tested for HIV, while HAC received more migrants and health-care workers. HRSB-participants were more commonly younger, males, non-Jewish, with lower income, previously tested for HIV, reported more sexual partners, payed for sex or used drugs. Conclusions MSM and HRSB-individuals were more likely to be tested in JOH, while migrants and health-care workers in HAC, possibly due to the geographic location, reputation and specific atmosphere. In order to encourage HIV-tests among HRSB and non-Jews, additional interventions should be employed, including outreach activities, extending opening hours and reducing testing costs should be employed.

Background: previous worldwide reports indicated a substantial short-term reduction in various respiratory infections during the early phase of the SARS-CoV-2 pandemic. Aims: exploring the long-term impact of the COVID-19 pandemic on respiratory pathogens. Methods: retrospective analysis of bacterial and viral positivity rate in respiratory samples, between 1 January 2017–30 June 2022 in a tertiary hospital in Jerusalem, Israel. Results: A decline in overall respiratory tests and positivity rate was observed in the first months of the pandemic. Respiratory isolations of Hemophilus influenza and Streptococcus pneumoniae were insignificantly affected and returned to their monthly average by November 2020, despite a parallel surge in COVID-19 activity, while Mycoplasma pneumoniae was almost eliminated from the respiratory pathogens scene. Each viral pathogen acted differently, with adenovirus affected only for few months. Human-metapneumovirus and respiratory-syncytial-virus had reduced activity for approximately a year, and influenza A virus resurged in November 2021 with the elimination of Influenza-B. Conclusions: After an immediate decline in non-SARS-CoV-2 respiratory infections, each pathogen has a different pattern during a 2-year follow-up. These patterns might be influenced by intrinsic factors of each pathogen and different risk reduction behaviors of the population. Since some of these measures will remain in the following years, we cannot predict the timing of return to pre-COVID-19 normalcy.

Oral health behavior and risks during pregnancy and after birth affect the oral health of babies and toddlers. We examined the oral and gingival health and caries prevalence of 150 postpartum women shortly after giving birth and assessed their knowledge of oral hygiene using a questionnaire. We also compared the oral health knowledge of nulliparous and multiparous women. Although most participants (98.0%) understood the importance of maintaining oral hygiene in children, their overall knowledge of oral health was medium–low, regardless of the number of previous pregnancies. Only 4.6% of women received oral health advice from their obstetrician during their pregnancy. Most participants had a high gingival index score, which correlated with dental pain during pregnancy. In contrast, the number of decayed, missing and filled teeth was significantly lower in first-time mothers. There was a statistically significant positive correlation between women who regularly visit their dentist and those who regularly take their children to the dentist. Expecting mothers should be educated about their own oral health and that of their developing fetus and children. Raising awareness among obstetricians with regards to this topic may be an effective way to achieve this.

In this mini-review, we highlight selected research by the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence “Precision Medicine in Chronic Inflammation” focusing on clinical sequencing and the clinical utility of polygenic risk scores as well as its implication on precision medicine in the field of the inflammatory diseases inflammatory bowel disease, atopic dermatitis and coronary artery disease. Additionally, we highlight current developments and discuss challenges to be faced in the future. Exemplary, we point to residual challenges in detecting disease-relevant variants resulting from difficulties in the interpretation of candidate variants and their potential interactions. While polygenic risk scores represent promising tools for the stratification of patient groups, currently, polygenic risk scores are not accurate enough for clinical setting. Precision medicine, incorporating additional data from genomics, transcriptomics and proteomics experiments, may enable the identification of distinct disease pathogeneses. In the future, data-intensive biomedical innovation will hopefully lead to improved patient stratification for personalized medicine.

Aim Combined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines. Purpose Characterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey. Methods A cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment. Results 176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment in 2019. 2DR that included INSTI and PI were more commonly used in cases of drug resistance, while a combination of INSTI and NNRTI was used in all other 2DR indications. A switch to 2DR induced a mean CD4 T cell increase from 599 cells/μl at treatment initiation to 680 cells/μl at 96 weeks of treatment pConclusions 2DR in a large-scale real-life nation-wide survey proved to be safe and effective. Most 2DRs, other than PI and INSTI, were similarly effective in suppressing HIV viremia and in elevating CD4 T cell counts.

Introduction: Accelerated bone loss and osteoporosis are multifactorial comorbidities related to HIV and its treatments; however, their mechanisms remain elusive. Identifying HIV treatments that are differentially linked to osteoporosis risk, and clinical factors associated with HIV-related osteoporosis may enable optimizing anti-retroviral treatment (ART) and anti-osteoporosis therapy in preventing or treating this debilitating complication. This study aims to evaluate the dynamics of bone turnover markers after initiation of two commonly used antiretroviral regimens. Methods: A prospective matched cohort study. Thirty treatment-naïve male patients (mean age 40 ± 10y) who initiated treatment with truvada (tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)) + raltegravir or TDF/FTC + efavirenz were included in the study. Control group included 15 treatment-naive HIV patients. Serum morning fasting level of P1NP and CTX were measured 0, 1, 6, and 12 months after treatment initiation in the two study groups, and at 0, 6 and 12 months in the control group. Results: In both treatment groups, but not in the control group, both markers increased significantly over time with no difference in BTM between patients treated with raltegravir or efavirenz. Levels of P1NP were statistically higher at 6 and 12 months after treatment initiation in both treatment groups compared to the controls, while CTX during treatment increased in both treatment groups but was significantly higher only in the raltegravir treatment group after 12 months. The ratio of area under the curve of P1NP/CTX correlated with CD4 increment. Conclusions: Treatment initiation with raltegravir or efavirenz combined with TDF/FTC is associated with increased bone turnover. Thus, therapy that optimize bone turnover is needed to reduce bone loss at this vulnerable period and improve long-term bone health.

Inclusion of bovine-derived milk fat globule membrane (bMFGM) or bMFGM components in infant formulas (IFs) may support healthy brain development. This double-blind, prospective trial evaluated growth, tolerance, and iron status in infants receiving added bMFGM and modified protein, iron, and arachidonic acid (ARA) concentrations in IF. Healthy term infants were randomized to: control (marketed, routine cow’s milk-based IF/100 kcal: 2.1 g protein, 1.8 mg iron, 34 mg ARA) or INV-MFGM (investigational cow’s milk-based IF/100 kcal: 1.9 g protein, 1.2 mg iron, 25 mg ARA and whey protein-lipid concentrate, 5 g/L (source of bMFGM)). Anthropometrics, stool characteristics, fussiness, and gassiness through day 365 and blood markers of iron status at day 365 were evaluated. The primary outcome was rate of weight gain from 14–120 days of age. Of 373 infants enrolled (control: 191, INV-MFGM: 182), 275 completed the study (control: 141; INV-MFGM: 134). No group differences in growth rate (g/day) from day 14–120 or study discontinuation were detected. Few group differences in growth or parent-reported fussiness, gassiness, or stool characteristics were detected. No group differences were detected in hemoglobin, hematocrit, or incidence of anemia. In healthy term infants, bMFGM and modified protein, iron, and ARA concentrations in a cow’s milk-based IF were well-tolerated, associated with adequate growth throughout the first year of life, and supported normal iron status at one year of age.

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis,

The recognition of the microbiota complexity and their role in the evolution of their host is leading to the popularization of the holobiont concept. However, the coral holobiont (host and its microbiota) is still enigmatic and unclear. Here, we explore the complex relations between different holobiont members of a mesophotic coral Euphyllia paradivisa. We subjected two lines of the coral—with photosymbionts, and without photosymbionts (apo-symbiotic)—to increasing temperatures and to antibiotics. The different symbiotic states were characterized using transcriptomics, microbiology and physiology techniques. The bacterial community’s composition is dominated by bacteroidetes, alphaproteobacteria, and gammaproteobacteria, but is dependent upon the symbiont state, colony, temperature treatment, and antibiotic exposure. Overall, the most important parameter determining the response was whether the coral was a symbiont/apo-symbiotic, while the colony and bacterial composition were secondary factors. Enrichment Gene Ontology analysis of coral host’s differentially expressed genes demonstrated the cellular differences between symbiotic and apo-symbiotic samples. Our results demonstrate the significance of each component of the holobiont consortium and imply a coherent link between them, which dramatically impacts the molecular and cellular processes of the coral host, which possibly affect its fitness, particularly under environmental stress.

Specialized prokaryotes performing biological dinitrogen (N2) fixation (“diazotrophs”) provide an important source of fixed nitrogen in oligotrophic marine ecosystems such as tropical and subtropical oceans. In these waters, cyanobacterial photosynthetic diazotrophs are well known to be abundant and active, yet the role and contribution of non-cyanobacterial diazotrophs are currently unclear. The latter are not photosynthetic (here called “heterotrophic”) and hence require external sources of organic matter to sustain N2 fixation. Here we added the photosynthesis inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) to estimate the N2 fixation potential of heterotrophic diazotrophs as compared to autotrophic ones. Additionally, we explored the influence of dissolved organic matter (DOM) on these diazotrophs along a coast to open ocean gradient in the surface waters of a subtropical coral lagoon (New Caledonia). Total N2 fixation (samples not amended with DCMU) ranged from 0.66 to 1.32 nmol N L−1 d−1. The addition of DCMU reduced N2 fixation by >90%, suggesting that the contribution of heterotrophic diazotrophs to overall N2 fixation activity was minor in this environment. Higher contribution of heterotrophic diazotrophs occurred in stations closer to the shore and coincided with the decreasing lability of DOM, as shown by various colored DOM and fluorescent DOM (CDOM and FDOM) indices. We tested the response of diazotrophs (in terms of nifH gene expression and bulk N2 fixation rates) upon the addition of a mix of carbohydrates (“DOC” treatment), amino acids (“DON” treatment), and phosphonates and phosphomonesters (“DOP” treatment). While nifH expression increased significantly in Trichodesmium exposed to the DOC treatment, bulk N2 fixation rates increased significantly only in the DOP treatment. The lack of nifH expression by gammaproteobacteria, in any of the DOM addition treatments applied, questions the contribution of non-cyanobacterial diazotrophs to fixed nitrogen inputs in the New Caledonian lagoon. While the metabolism and ecology of heterotrophic diazotrophs is currently elusive, a deeper understanding of their ecology and relationship with DOM is needed in the light of increased DOM inputs in coastal zones due to anthropogenic pressure.

Foot and mouth disease (FMD) epidemics recur in Israel almost every year. Wild even-toed ungulates are seldom affected during these epidemics. The sero-prevalence of FMD in wild ungulates during 2000 and 2005-13 was estimated using anti non-structural proteins (NSP) ELISA. Overall, 209 samples were tested, comprising sera of 120 wild boar (Sus scrofa lybicus), 64 mountain gazelles (Gazella gazella gazella), six water buffaloes (Bubalus bubalis), and 19 Persian fallow deer (Dama dama mesopotamica). None of the tested animals presented clinical signs of FMD during blood collection. Sixteen samples (7.7% (95% confidence interval (CI95%) = 4.4 - 12.1%)) were found to be sero-positive. Fifteen out of 120 samples (12.5%) from wild boar were sero-positive, compared with only one out of 89 samples (1.1%) from all other species combined (Fisher's Exact test: p=0.003). Most of the positive samples obtained from wild boar (13/15 (86.7%)) were collected during 2007 and analysis was restricted to that year and species only. The sero-prevalence of FMD in this species during 2007 was estimated at 54.2% (CI95%=32.8 - 74.5%; n=24). A significant infection cluster, comprising nine sero-positive samples collected in three different locations, was identified in the north-eastern part of Israel. These findings indicate that wild boar were affected during the 2007 FMD epidemic, even though wild boar presenting FMD typical clinical signs were not observed during that year. The actual role of wild boar in the spread of FMD virus in this epidemic, however, could not be determined. The negligible sero-prevalence of FMD found for all other surveillance years indicates that ongoing circulation of FMD among wildlife in Israel is unlikely. It is concluded that while the role of wildlife species in the dynamics of FMD in Israel is usually limited, there might be occasions in which wildlife play a part in the spread of the virus.

Various surfaces associated with the storage and packing of food are known to harbor distinct bacterial pathogens. Conspicuously absent among the plethora of studies implicating food packaging materials and machinery is the study of corrugated cardboard packaging, the worldwide medium for transporting fresh produce. In this study, we observed the microbial communities of three different store-bought fruits and vegetables, along with their analogue cardboard packaging using high throughput sequencing technology. We further developed an anti-biofilm polymer meant to coat corrugated cardboard surfaces and mediate bacterial biofilm growth on said surfaces. Integration of a novel thiazolidinedione derivative into the acrylic emulsion polymers was assessed using Energy Dispersive X-ray Spectrometry analysis and surface topography was visualized and quantified on corrugated cardboard surfaces. Biofilm growth was measured using q-PCR targeting the gene encoding 16s rRNA. Additionally, architectural structure of the biofilm was observed using SEM. The uniform integration of the thiazolidinedione derivative TZD-6 was confirmed, and it was determined via q-PCR to reduce biofilm growth by ~80% on tested surfaces. A novel and effective method for reducing microbial load and preventing contamination on food packaging is thereby proposed.

Our experience with the natural world, as composed of ordered entities, implies that perception captures relationships between image parts. For instance, regularities in the visual scene are rapidly identified by our visual system. Defining the regularities that govern perception is a basic, unresolved issue in neuroscience. Mathematically, perfect regularities are represented by symmetry (perfect order). The transition from ordered configurations to completely random ones has been extensively studied in statistical physics, where the amount of order is characterized by a symmetry-specific order parameter. Here we applied tools from statistical physics to study order detection in humans. Different sets of visual textures, parameterized by the thermodynamic temperature in the Boltzmann distribution, were designed. We investigated how much order is required in a visual texture for it to be discriminated from random noise. The performance of human observers was compared to Ideal and Order observers (based on the order parameter). The results indicated a high consistency in performance across observers, much below that of the Ideal observer, but well approximated by the Order observer. Overall, we provide a novel quantitative paradigm to address order perception. Our findings, based on this paradigm, suggest that the statistical physics formalism of order captures regularities to which the human visual system is sensitive. An additional analysis revealed that some order perception properties are captured by traditional texture discrimination models according to which discrimination is based on integrated energy within maps of oriented linear filters.

HIV in Israel started with a subtype-B epidemic among men who have sex with men, followed in the 1980s and 1990s by introductions of subtype C from Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from the former Soviet Union (FSU, most often acquired by intravenous drug use). The epidemic matured over the last 15 years without additional large influx of exogenous infections. Between 2005 and 2013 the number of infected men who have sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding contemporary spread is essential for effective public health planning.We analyzed demographic and virologic data from 1,427 HIV-infected individuals diagnosed with HIV-I during 1998-2012. HIV phylogenies were reconstructed with maximum-likelihood and Bayesian methods.Subtype-B viruses, but not A or C, demonstrated a striking number of large clusters with common ancestors having posterior probability ≥0.95, including some suggesting presence of transmission networks. Transmitted drug resistance was highest in subtype B (13%). MSM represented a frequent risk factor in cross-ethnic transmission, demonstrated by the presence of Israeli-born with non-B virus infections and FSU immigrants with non-A subtypes.Reconstructed phylogenetic trees demonstrated substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C, reflecting differences in transmission dynamics linked to HIV transmission categories. Cross-ethnic spread occurred through multiple independent introductions, with MSM playing a prevalent role in the transmission of the virus. Such data provide a baseline to track epidemic trends and will be useful in informing and quantifying efforts to reduce HIV transmission.

Glycinergic inhibition plays a central role in the auditory brainstem circuitries involved in sound localization and in the encoding of temporal action potential firing patterns. Modulation of this inhibition has the potential to fine-tune information processing in these networks. Here we show that nitric oxide (NO) signalling in the auditory brainstem (where activity-dependent generation of NO is documented) modulates the strength of inhibition by changing the chloride equilibrium potential. Recent evidence demonstrates that large inhibitory postsynaptic currents (IPSCs) in neurons of the superior paraolivary nucleus (SPN) are enhanced by a very low intracellular chloride concentration, generated by the neuronal potassium chloride co-transporter (KCC2) expressed in the postsynaptic neurons. Our data show that modulation by NO caused a 15mV depolarizing shift of the IPSC reversal potential, reducing the strength of inhibition in SPN neurons, without changing the threshold for action potential firing. Regulating inhibitory strength, through cGMP-dependent changes in the efficacy of KCC2 in the target neuron provides a postsynaptic mechanism for rapidly controlling the inhibitory drive, without altering the timing or pattern of the afferent spike train. Therefore, this NO-mediated suppression of KCC2 can modulate inhibition in one target nucleus (SPN), without influencing inhibitory strength of other target nuclei (MSO, LSO) even though they are each receiving collaterals from the same afferent nucleus (a projection from the medial nucleus of the trapezoid body, MNTB).

Magnetotactic bacteria (MTB) are Gram-negative bacteria that can navigate along geomagnetic fields. This ability is a result of a unique intracellular organelle, the magnetosome. These organelles are composed of membrane-enclosed magnetite (Fe3O4) or greigite (Fe3S4) crystals ordered into chains along the cell. Magnetosome formation, assembly and magnetic nano-crystal biomineralization are controlled by magnetosome-associated proteins (MAPs). Most MAP-encoding genes are located in a conserved genomic region – the magnetosome island (MAI). The MAI appears to be conserved in all MTB that were analyzed so far, although the MAI size and organization differs between species. It was shown that MAI deletion leads to a non-magnetic phenotype, further highlighting its important role in magnetosome formation. Today, about 28 proteins are known to be involved in magnetosome formation, but the structures and functions of most MAPs are unknown. To reveal the structure-function relationship of MAPs we used bioinformatics tools in order to build homology models as a way to understand their possible role in magnetosome formation. Here we present a predicted 3D structural models’ overview for all known Magnetospirillum gryphiswaldense strain MSR-1 MAPs.

BACKGROUND: Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment. METHODS: Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS. RESULTS: 607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P

We measured N2 fixation rates from oceanic zones that have traditionally been ignored as sources of biological N2 fixation; the aphotic, fully oxygenated, nitrate (NO3-)-rich, waters of the oligotrophic Levantine Basin (LB) and the Gulf of Aqaba (GA). N2 fixation rates measured from pelagic aphotic waters to depths up to 720 m, during the mixed and stratified periods, ranged from 0.01 nmol N L-1 d-1 to 0.38 nmol N L-1 d-1. N2 fixation rates correlated significantly with bacterial productivity and heterotrophic diazotrophs were identified from aphotic as well as photic depths. Dissolved free amino acid amendments to whole water from the GA enhanced bacterial productivity by 2to 3.5 and N2 fixation rates by ~ 2 fold in samples collected from aphotic depths while in amendments to water from photic depths bacterial productivity increased 2 to 6 fold while N2 fixation rates increased by a factor of 2 to 4 illustrating that both BP an heterotrophic N2 fixation are carbon limited. Experimental manipulations of aphotic waters from the LB demonstrated a significant positive correlation between transparent exopolymeric particles (TEP) concentration and N2 fixation rates. This suggests that sinking organic material and high carbon (C): nitrogen (N) micro-environments (such as TEP-based aggregates or marine snow) could support high heterotrophic N2 fixation rates in oxygenated surface waters and in the aphotic zones. Indeed, our calculations show that aphotic N2 fixation accounted for 37 to 75 % of the total daily integrated N2 fixation rates at both locations in the Mediterranean and Red Seas with rates equal or greater to those measured from the photic layers. Moreover, our results indicate that that while N2 fixation may be limited in the surface waters, aphotic, pelagic N2 fixation may contribute significantly to new N inputs in other oligotrophic basins, yet it is currently not included in regional or global N budgets.

High throughput sequencing (HTS) yields tens of thousands to millions of sequences that require a large amount of pre-processing work to clean various artifacts. Such cleaning cannot be performed manually. Existing programs are not suitable for immunoglobulin (Ig) genes, which are variable and often highly mutated. This paper describes Ig-HTS-Cleaner (Ig High Throughput Sequencing Cleaner), a program containing a simple cleaning procedure that successfully deals with pre-processing of Ig sequences derived from HTS, and Ig-Indel-Identifier (Ig Insertion – Deletion Identifier), a program for identifying legitimate and artifact insertions and/or deletions (indels). Our programs were designed for analyzing Ig gene sequences obtained by 454 sequencing, but they are applicable to all types of sequences and sequencing platforms. Ig-HTS-Cleaner and Ig-Indel-Identifier have been implemented in Java and saved as executable JAR files, supported on Linux and MS Windows. No special requirements are needed in order to run the programs, except for correctly constructing the input files as explained in the text. The programs' performance has been tested and validated on real and simulated data sets.

In the healthy primate, neurons of the external and internal segments of the globus pallidus (GP) present a primarily irregular firing pattern, and a negligible level of synchrony is observed between pairs of neurons. This holds even for neighboring cells, despite their higher probability to receive common inputs and to innervate each other via lateral connectivity. In the parkinsonian primate, this changes drastically, and many pairs of GP cells show synchronous oscillations. To address the relation between distance and synchrony in the parkinsonian state, we compared the synchrony of discharge of close pairs of neurons, recorded by the same electrode, with remote pairs, recorded by different ones. However, spike trains of neighboring cells recorded by the same extracellular electrode exhibit the shadowing effect; i.e., lack of detection of spikes that occur within a few milliseconds of each other.Here, we demonstrate that the shadowing artifact can both induce apparent correlations between non-correlated neurons, as well as conceal existing correlations between neighboring ones. We therefore introduced artificial shadowing in the remote pairs, similar to the effect we observed in the close ones. After the artificial shadowing, neighboring cells did not show a higher tendency to oscillate synchronously than remote ones. On the contrary, the average percentage (over all sessions) of artificially shadowed remote pairs exhibiting synchronous oscillations was 35.4% compared to 17.2% in the close ones. Similar trend was found when the unshadowed remote pairs were separated according to the estimated distance between electrode tips: 29.9% of pairs at approximate distance of less than 750 µm were significantly synchronized, in comparison with 28.5% of the pairs whose distance was more than 750 µm.We conclude that the synchronous oscillations in the GP of MPTP treated primates are homogenously distributed.

Background: Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients., Methods: Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization., Results: 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO 2 /FiO 2 was similar between men and women (228 [IQR, 134-273] vs 238 mmHg [150-281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan-Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687)., Conclusion: Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.

Introduction: The aim of the present investigation was to retrospectively evaluate the utilization of Swan-Ganz catheter during orthotopic liver transplantation as opposed to FloTrac/Vigileo in selected cases, comparing a number of clinical outcomes across postoperative hospitalization., Materials and Methods: Before 2015 all recipients received pulmonary artery catheter (Swan-Ganz group, n = 109). After 2015 Swan-Ganz was used only if coronary artery disease or high-grade portal hypertension or Child-Pugh C were present; the remaining recipients were assigned to FloTrac/Vigileo monitoring (Mini group, n =100). A number of clinical outcomes were considered., Results: Donor's Risk Index was similar between groups (median value 1.7, P = .27). Anthropometric characteristics of the recipients were similar in the 2 groups. There were no significant differences in the proportion of patients with Child-Pugh C (P = .873), coronary artery disease (P = .18), and grade of portal hypertension (P = .733). The Model for End-Stage Liver Disease score was slightly higher in the Mini group: (9 [7-11] vs 9 [8-12], Swan-Ganz vs Mini, respectively, P < .035). Swan-Ganz utilization decreased over time (92% vs 26%, Swan-Ganz vs Mini, P < .001). Upon admission to the intensive care unit, patients of the Mini group presented a higher SAPS II score with similar values of Sequential Organ Failure Assessment score. Days on mechanical ventilation were similar between groups. The incidence of graft failure was similar between groups (2% vs 5%, Swan-Ganz and Mini group respectively, P = .376). Recipients' hospital length of stay was similar (13 days [11-19] vs 14 [11-20], P < .083)., Conclusions: Our data suggest that the intraoperative utilization of FloTrac/Vigileo for oncologic patients with low grade end stage liver disease is reasonably safe., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Dental implants and bone augmentation are well-established procedures used for oral rehabilitation. There is an increasing interest in biological mediators used topically for prevention of bone resorption maybe enhancement of osseointegration of dental implants. The purpose of the manuscript is to describe preliminarily the effect of bisphosphonates on the ossification pattern of bone grafts in a rat model., Material and Methods: Twenty Wistar-derived male rats were divided into 2 groups study and control. Bone substitute was added to mandibular defects and was covered by a resorbable collagen membrane. In the study group, the membrane was soaked with bisphosphonates suspension. In the control group, the membrane was soaked with saline solution. Radiographic and histomorphometric evaluation were performed., Results: Radiographically, it was found that bone density was significantly higher in the study group. Histomorphometric analysis revealed a trend of higher bone volume fraction along with reduced bone substitute volume fraction in the study group, and increased number of osteoclasts and blood vessels in the control group., Conclusions: Within the limitations of our study it was found that there is a trend of increasing bone quantity and radiographic bone density by application of bisphosphonates.