A novel schistosome species hosted by Planorbella (Helisoma) trivolvis is the most widespread swimmer's itch-causing parasite in Michigan inland lakes.

Cercarial dermatitis ('swimmer's itch'; SI), characterized by small itchy bumps caused by schistosome parasites of birds and mammals, is a common problem in Michigan. Research on avian schistosomes began nearly 100 years ago in Michigan inland lakes, yet scientists are still uncovering basic biological information including the identification of local snail and parasite species that cause SI. Previous research primarily focused on lakes in the northern half of Michigan's lower peninsula, although SI occurs throughout the state. We surveyed snails and snail-borne trematodes in lakes across Michigan's lower peninsula and used quantitative polymerase chain reaction analysis of filtered water samples to identify parasites to the species level, including a recently discovered parasite species that uses the snail Planorbella (Helisoma) trivolvis as its intermediate host. Most SI mitigation efforts have focused on a parasite species hosted by the snail Lymnaea catescopium ( = Stagnicola emarginata); however, lymnaeid snails and their associated schistosome species were largely restricted to northern lakes. In contrast, P. trivolvis and its associated parasite species were common in both northern and southern Michigan lakes. A third schistosome species associated with physid snails was also present at low levels in both northern and southern lakes. These results indicate that the recently discovered parasite species and its planorbid snail intermediate host may be more important drivers of Michigan SI than previously thought, possibly due to increased definitive host abundance in recent decades. These results have potentially important implications for SI mitigation and control efforts.

A hedgehog pathway-dependent gene signature is associated with poor clinical outcomes in Luminal A breast cancer.

PURPOSE: High expression of glioma-associated oncogene homolog-1 (GLI1) is associated with poor prognosis in estrogen receptor (ER) positive breast cancers. We sought to define a GLI1-dependent gene signature in ER-positive tumors that could further stratify patients at higher risk for disease recurrence and potentially lead to novel combination therapies. METHODS: We identified an inverse correlation between GLI1 expression and distant disease-free survival (DFS) using a dataset developed at MD Anderson Cancer Center (Hatzis dataset) containing clinical data from 508 breast cancer patients. Using a qPCR-based microarray platform, we identified genes differentially regulated by GLI1 in MCF7 cells and then determined if expression of these genes correlated with GLI1 expression in patient tumor samples. Statistical comparison between the groups was performed by ANOVA. Direct comparison of two groups was done by a two-tailed t test. Correlations between variables were done by Pearson's method. RESULTS: Expression of GLI1 and its target genes correlated significantly with worse distant DFS in breast cancer patients with Luminal A molecular subtype. Particularly, co-expression of GLI1 with EGFR and/or SNAI1, two of the identified GLI1 targets, was predictive of worse distant DFS in this subtype. Furthermore, patients with Luminal A tumors with a high GLI1 signature had a shorter distant DFS compared to the Luminal B subtype and the outcome for this group was comparable to patients with HER2-positive or basal-like tumors. CONCLUSION: We have identified a novel GLI1 gene signature that is associated with worse clinical outcomes among the patients with Luminal A subtype of breast cancer.

Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials.

Gut microbiota is important for maintaining body weight. Modulation of gut microbiota by probiotics may result in weight loss and thus help in obesity treatment. The aim of this systematic review was to evaluate the effects of Lactobacillus on weight loss and/or fat mass in overweight adults. A search was performed on the Medline (PubMed) and Scopus electronic databases using the search terms: 'probiotics', 'Lactobacillus, 'obesity', 'body weight changes', 'weight loss', 'overweight', 'abdominal obesity', 'body composition', 'body weight', 'body fat' and 'fat mass'. In the total were found 1567 articles, but only 14 were included in this systematic review. Of these nine showed decreased body weight and/or body fat, three did not find effect and two showed weight gain. Results suggest that the beneficial effects are strain dependent. It can highlight that Lactobacillus plantarum and Lactobacillus rhamnosus when combined with a hypocaloric diet, L. plantarum with Lactobacillus curvatus, Lactobacillus gasseri, Lactobacillus amylovorus, Lactobacillus acidophilus and Lactobacillus casei with phenolic compounds, and multiple species of Lactobacillus.

HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Estimation of mating system parameters in an evolving gynodioecous population of cultivated sunflower (Helianthus annuus L.).

Cultivated plants have been molded by human-induced selection, including manipulations of the mating system in the twentieth century. How these manipulations have affected realized parameters of the mating system in freely evolving cultivated populations is of interest for optimizing the management of breeding populations, predicting the fate of escaped populations and providing material for experimental evolution studies. To produce modern varieties of sunflower (Helianthus annuus L.), self-incompatibility has been broken, recurrent generations of selfing have been performed and male sterility has been introduced. Populations deriving from hybrid-F1 varieties are gynodioecious because of the segregation of a nuclear restorer of male fertility. Using both phenotypic and genotypic data at 11 microsatellite loci, we analyzed the consanguinity status of plants of the first three generations of such a population and estimated parameters related to the mating system. We showed that the resource reallocation to seed in male-sterile individuals was not significant, that inbreeding depression on seed production averaged 15-20% and that cultivated sunflower had acquired a mixed-mating system, with ∼50% of selfing among the hermaphrodites. According to theoretical models, the female advantage and the inbreeding depression at the seed production stage were too low to allow the persistence of male sterility. We discuss our methods of parameter estimation and the potential of such study system in evolutionary biology.

The Arterial Anastomosis Between Deep Inferior Epigastric Artery and Small Polar Renal Artery in Kidney Transplantation: A Case Report.

The presence of multiple renal arteries is the most common form of vascular anomalies found in donor kidneys. In rare cases, small renal polar arteries may be found. They can be anastomosed with deep inferior epigastric arteries, resulting in vascular augmentation of transplanted kidneys and contributing to better graft function. Renal perfusion may be increased via 2 types of vascular reconstruction known as "turbocharging" and "supercharging". Turbocharging uses vascular sources within the same organ area, whereas supercharging uses distant vascular sources. Using additional vessels can either complicate the surgery or, contradictorily, ease the way of procedure. This case study presents a kidney transplant during which arterial anastomosis between deep inferior epigastric artery and small polar renal artery was performed.

Outcomes of Kidney Transplant During the SARS-CoV-2 Pandemic at 1 Center in Poland.

The SARS-CoV-2 pandemic has significantly affected the number of transplanted organs worldwide. The rules and restrictions related to transplantation activities in Poland are included in the updated guidelines of the Polish Organizational and Coordination Centre for Transplantation. Our clinic faces the same problems as the rest of the hospitals in the country. Not only are the number of recipients falling, but there are also numerous restrictions concerning, among other things, qualification of donors and recipients and even preparation of centers for long-term care in the event of infection of organ recipients with the SARS-CoV-2 virus. Statistics showed, after an initial fall in the number of kidneys transplanted, a temporary normalization during the summer months, only to record a fall again with an increase in new cases of COVID-19. A total of 29 kidneys were transplanted at our center between March and December 2020. Kidney transplantation is not only linked to the operation itself, but also to the follow-up care of the recipients. Reduced immunity among recipients due to immunosuppressive treatment as well as comorbidities among recipients contribute to this group being at increased risk of symptomatic SARS-CoV-2 infection. The number of cases of SARS-CoV-2 infection among kidney transplant recipients at our center was 7, of which we recorded 2 deaths due to COVID-19 in the period after kidney transplant. Postoperative complications probably related to previous SARS-CoV-2 infection occurred in 1 patient.

Higher-order optical resonance node detection of integrated disk microresonator.

We have demonstrated higher-order optical resonance node detection by using an integrated disk microresonator from through port of the coupling bus waveguide. In addition to the fundamental mode, the disk resonator has higher-order whispering gallery modes. The excited second-order higher-order mode has a node at the position where the electromagnetic energy of the fundamental mode is close to a maximum. This high resolution measurement of optical resonance mode profile has a variety of applications for optical sensing and detection. The self-referencing characteristics of the two optical resonance modes have potential to achieve optical detection independent of external perturbation, such as temperature change.

Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy.

We examined the pathogenic significance of the latent viral reservoir in the resting CD4+ T cell compartment of HIV-1-infected individuals as well as its involvement in the rebound of plasma viremia after discontinuation of highly active anti-retroviral therapy (HAART). Using heteroduplex mobility and tracking assays, we show that the detectable pool of latently infected, resting CD4+ T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued. In the majority of patients examined, the rebounding plasma virus was genetically distinct from both the cell-associated HIV RNA and the replication-competent virus within the detectable pool of latently infected, resting CD4 + T cells. These results indicate the existence of other persistent HIV reservoirs that could prompt rapid emergence of plasma viremia after cessation of HAART and underscore the necessity to develop therapies directed toward such populations of infected cells.

Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes.

The receptor for macrophage colony stimulating factor (CSF-1), the c-fms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-fms proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-1, c-ets-2, and the macrophage-specific factor PU.1, but not the ets-factor PEA3, trans-activated the c-fms proximal promoter. On the other hand c-myb repressed proximal promoter activity in macrophages and blocked the action of c-ets-1 and c-ets-2. Basal c-fms promoter activity was almost undetectable in the M1 leukaemia line, which expressed high levels of c-myb, but was activated as cells differentiated in response to leukemia inhibitory factor and expressed c-fms mRNA. The repressor function of c-myb depended on the COOH-terminal domain of the protein. We propose that ets-factors are necessary for the tissue-restricted expression of c-fms and that c-myb acts to ensure correct temporal expression of c-fms during myeloid differentiation.

Using linked markers to estimate the genetic age of a volunteer population: a theoretical and empirical approach.

Volunteers deriving from unharvested seeds of a crop can lead to persistent feral populations and participate in genetic exchanges across the agro-ecosystem, both between crop varieties and between crops and their wild relatives. A first step to understand the importance of volunteers is to characterize their capacity to reproduce autonomously for several generations. For that purpose, we constructed and evaluated a maximum-likelihood method to estimate the genetic age of a population deriving from one of the most common field crop type: an F1-hybrid variety. The method estimates the number of reproduction cycles that occurred since the cultivation of that variety. It makes use of genotypic data at a number of linked microsatellite loci pairs, thus exploiting the recombination of parental haplotypes, which is expected to occur as the population is reproducing. Estimates with moderate bias and variance were found for a broad range of parameter values in simulations, and the method revealed robust to some deviations from the assumptions of the underlying model. We propose a specific procedure to test the hypothesis of persistence, that is has a given volunteer population experienced more than one cycle of reproduction since the F1-hybrid state? The method was applied to both an experimental and a natural sunflower volunteer population and revealed promising, considering these ideal case studies. Possible further developments toward more complex natural systems are discussed.

Simulation of wastewater treatment plant within integrated urban wastewater models.

In the federal state of Hesse in Germany the application of an integrated software modelling framework is becoming part of the planning process to attain legal approval for the operation of combined sewer systems. The software allows for parallel simulation of flow and water quality routing in the sewer system and in receiving rivers. It combines existing pollution load model approaches with a simplified version of the River Water Quality Model No. 1 (RWQM1). Comprehensive simulation of the wastewater treatment plant (WWTP) is not considered yet. The paper analyses alternatives for the implementation of a WWTP module to model activated sludge plants. For both primary and secondary clarifiers as well as for the activated sludge process concepts for the integration into the existing software framework were developed. The activated sludge concept which uses a linearized version of the well known ASM1 model is presented in detail.

Transplantation of a Kidney With Duplicated Ureter Harvested From a Donor With Vascular Anomaly in the Form of Double Inferior Vena Cava: A Case Report.

During the organ procurement procedure, a surgeon encounters anatomic anomalies not very often but also not uncommonly. These changes may put the success of the transplant into question. Despite the thorough diagnosis of the potential donor, these anomalies are often diagnosed during organ donation. In our paper we present a case of kidney transplantation with duplicated ureter. The organ was collected from a donor with duplicated inferior vena cava. After transplantation, the kidney functioned immediately. Taking into consideration the well-being of the recipient, organs with anatomic abnormalities should be carefully considered for transplantation. This is especially important when there is a constant shortage of organs for transplantation.

Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.

Are we taking proper care of living donors? A follow-up study of living kidney donors in Poland and further management proposal.

OBJECTIVE: The first kidney transplantation was performed in Poland in 1966. Since that time approximately 11,000 patients have undergone the procedure, but most of them have received the kidney from deceased donors; only 342 procedures utilized living donors (LD; 2.7%). The aim of this study was to review the results of a LD follow-up in Poland. PATIENTS AND METHODS: A questionnaire was sent to 11 centers that had performed 197 LD kidney transplantations during the last 10 years. The donors, who were all genetically or emotionally related, were 23 to 61 years old. No donor showed an abnormality regarding cardiovascular function or metabolic abnormalities. RESULTS: The 6 centers that responded reported data on 118 donors. In 2 centers no donor follow-up was available. Eleven of 118 donors did not attend the control visits. Follow-up of the remaining donors ranged from 2 to 8 years. Four donors died at 4 to 5 years after nephrectomy due to cerebral hemorrhage, brain tumor, stomach cancer, or car accident. The overall mean serum creatinine had increased from 0.8 to 1.25 mg/dL, but 2 patients displayed a value >2 mg/dL. The calculated creatinine clearance (MDRD formula) had decreased from 95 to 65 mL/min (P < .05). In 3 donors proteinuria (>0.6 g/24 h) was observed at 3 to 5 years after donation. Of 3 patients who experienced mild hypertension, 2 required treatment. The remaining donors showed normal blood pressures. CONCLUSIONS: Since 2007, when the Living Donor Registry was introduced by law, transplant centers have been obliged to report data on each LD procedure together with follow-up data. All donors are life-insured (by Alianz SA) for 3 months from the time of transplantation. Stepwise interventional reno- and cardioprotection programs have been introduced after nephrectomy for LD, especially those with metabolic abnormalities at the time of donation.

Circulating adhesion molecules and purine nucleotides during kidney allograft reperfusion.

The impairment of organ function due to ischemia-reperfusion injury is still an important problem in solid organ transplantation. Numerous experimental and clinical studies of native organs have shown that ischemia-reperfusion constitutes an acute inflammatory process involving cell surface adhesion molecule expression. These markers are crucial for the recruitment and infiltration of effector cells into the postischemic tissue. Purines released by the postischemic tissue as the products of the degradation of high-energy nucleotides can be regarded as markers of disturbed energy metabolism. The aim of this study was to examine the correlation between circulating adhesion molecules and purine metabolites in graft renal vein plasma during 49 cases of kidney reperfusion. E-selectin, ICAM-1, and VCAM-1 concentrations correlated positively with hypoxanthine concentrations during reperfusion, whereas the concentrations of ICAM-1 correlated negatively with xanthine concentrations. The results of the present study suggested that the concentrations of adhesion molecules in the renal vein during reperfusion correlated with purine metabolites, reflecting metabolic changes in renal tissue.

Experience with autosomal dominant polycystic kidney disease in patients before and after renal transplantation: a 7-year observation.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of multiple cysts in both kidneys. Symptoms of the disease may arise either from the presence of cysts or from increasing loss of kidney function. First symptoms usually appear in the third decade of life: lumbar pain, urinary tract infections, arterial hypertension, or renal colic due to cyst rupture or coexistent nephrolithiasis. An early diagnosis, male gender, large kidneys by sonography, arterial hypertension, hematuria, and urinary tract infections are predictive factors of a faster progression of the disease. Our aim was to establish the indications for nephrectomy among symptomatic ADPKD patients before kidney transplantation and to assess the risks of posttransplantation complications among ADPKD patients without nephrectomy. PATIENTS AND METHODS: The observed group consisted of 183 patients with ADPKD among whom 50 (27.3%) underwent kidney transplantation during a 7-year observation period (2000-2007). Among those subjects were 3 groups: (I) nephrectomy preceding transplantation; (II) nephrectomy during kidney transplantation; and (III) without nephrectomy. RESULTS: Among group I before transplantation we observed: arterial hemorrhage, wound infections, and splenectomy 4 weeks after ADPKD nephrectomy; afterward we observed: urinary tract infections and contralateral cyst infection. Among group II we only observed 1 case of wound infection. Among group III we observed: ascending urinary tract infections, cyst infections, and cyst hemorrhage. Cyst hemorrhage and cyst infections led mainly to ADPKD kidney nephrectomy. During the observation time, 80.95% of grafts were functioning. CONCLUSIONS: Unilateral nephrectomy is a well-founded preliminary surgical treatment before kidney transplantation. Bilateral nephrectomy before or during transplantation eliminates ADPKD complications and does not significantly increase general complications. The greatest numbers of complications and of graft losses were observed among the group without pretransplantation nephrectomy.

Stage migration and pilot studies of reduced chemotherapy supported by positron-emission tomography findings suggest new combined strategies for stage 2 nonseminoma germ cell tumour.

OBJECTIVE: To examine the nodal (N+) vs extranodal (M+) staging in each of the International Germ Cell Consensus Classification Group (IGCCCG) subgroups in an audit of 437 patients treated in The Anglian Germ Cell Cancer Group, where chemotherapy was the primary management, as there is an increasingly earlier presentation of patients with less advanced disease who thus face potentially unnecessary treatment. PATIENTS AND METHODS: Clinicians from seven centres prospectively registered patients in a central database, and the follow-up was coordinated by one of the authors. RESULTS: Between 1982 and 2002, 436 patients (median follow-up 60 months) were registered; 63% of IGCCCG good risk (298), 42% of intermediate (62) and 8% poor risk (77) were stage II; 79% of N+M0 intermediate and poor risk cases (29) were alive, vs only 60% of M+ stage IV cases (92, P < 0.05). The trend was similar in IGCCCG good risk patients, with 92% of N+ stage II (156) alive vs only 85% (94) of stage IV M+ (not significant). The frequency of retroperitoneal lymph node dissection after chemotherapy increased from 26% (1983-1993) to 34% (1994-2002), and survival from 89% to 94%. There were no relapses in eight patients who elected to stop treatment after two courses. Four of six patients with positive findings on positron emission tomography had a durable complete response, assessed by standard uptake values, when tested at 72-96 h. CONCLUSION: Extra-lymphatic spread, although prognostically important within the IGCCCG subgroups, is only statistically significant for intermediate and poor risk combined. The observation that there might be N+ patients cured by two chemotherapy courses alone suggests that there might be opportunities to reduce the morbidity of treatment.

Does calcium channel blocker improvement of perfusion impact the functioning of kidney graft in early period after transplantation?

The aim of the study was to evaluate the influence of reduced vascular resistance following calcium channel blocker verapamil administration on kidney function at 3 months after transplantation. A group of 48 kidneys received 100 microg verapamil by injection directly into renal artery before starting perfusion. The control group included 48 paired kidneys without verapamil addition. Calcium channel blocker therapy with verapamil greatly decreased renal vascular resistance but it did not affect graft function. Administration of calcium channel blockers improved kidney function in the early period after transplantation. A better-functioning graft seems to be based more on metabolic than hemodynamic effects.

The Importance of New Generation Sequencing (NGS) HLA Typing in Renal Transplantation-Preliminary Report.

INTRODUCTION: Thanks to new generation sequencing (NGS) and expansion of HLA typing with additional loci, it will be possible to increase the effectiveness of graft survival and to avoid complications related to the immune system. New pharmacogenetic factors are still being researched to develop better immunosuppressive treatment. MATERIAL AND METHODS: The incidence of polymorphic HLA loci variants was established, based on a high-resolution NGS method in kidney graft recipients. Furthermore, haplotypic analysis between examined loci was conducted to type additional loci that may influence the transplantation result. A total of 120 kidney recipients were enrolled in the study. A commercial DNA extraction kit in Tubes (QIAamp DNA Blood Mini Kit Qiagen, Germany) was used to isolate DNA from the blood. Sequencing library preparation was done with TruSight HLA set. The Conexio computer program was used to analyse the results of HLA typing. RESULTS: The patients with alleles A*02:01:01, B*44:02:01, C*03:03:01, C*01:02:01, C*05:01:01, C*07:02:01, DQB1*03:03:02, DQB1*06:04:01, or with haplotypic variation A*25:01:01-B*18:01:01- C*15:01:01 were taking the highest doses of cyclosporine (CsA), in contrast to patients with allele B*18:01:01, DQB1*06:02:01, DQB1*02:02:01, or haplotypic variation A*02:01:01- B*44:02:01-C*01:01:01, who were taking the lowest doses. The highest dose of tacrolimus (TAC) was administered to patients with alleles A*68:01:02, A*29:01:01, B*07:02:01, B*35:02:01, B*38:01:01, DRB1*12:01:01, DQB1*05:03:01, or haplotypic variations A*02:01:01-B*57:01:01-C*07:01:01, A*03:01:01-B*07:02:01-C*13:01:01, A*29:02:01-B*44:03:01- C*07:01:01, and A*01:01:01-B*08:01:01-C*03:01:01. Additionally, it was established that HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPA1, and HLA-DQA1 show very slight polymorphism, which suggests that there is no need for their typing for transplantation purposes. Moreover, loci HLA-C, HLA-DQB1, and HLA-DPB1, which are not routinely examined in recipient-donor matching, show genetic variability that may increase the risk of transplant rejection or shortened graft life. CONCLUSIONS: Expanding the qualification procedure to include allele genotyping could allow clinicians to establish immunosuppressive treatment schemes that would be optimally suited for recipients' phenotype.