Grade 3 complications were infrequent, and all such cases eventua

Grade 3 complications were infrequent, and all such cases eventually had resolution of these effects with minor surgical intervention. It is important to note that no severe GI complications were encountered in this cohort, despite having had previous very high doses of EBRT. Local recurrence after definitive EBRT is not infrequent. It has been estimated that nearly one-third of patients who undergo EBRT will have positive post-treatment biopsies of the prostate, and 15% of patients who received 8100 cGy were

found to have positive biopsies (9). The consequences of locally recurrent disease after radiotherapy can be significant. In a report of the outcomes of locally Dabrafenib price recurrent prostate cancer after EBRT, Kuban et al. reported that nearly one-third of patients suffered from major complications associated with

local recurrence (10). Locally recurrent diseases pose as well a significant risk for the development of distant metastases [1], [9] and [11]. GSK126 research buy Often patients who have developed locally recurrent disease after radiotherapy are not candidates for salvage prostatectomy due to age or coexisting medical comorbidities. Salvage prostatectomy also carries a significant risk of rectal injury (16–58%), and 68% of patients will require the use of at least one pad for urinary incontinence (12). Long-term followup suggests that up to 54% of patients who undergo salvage prostatectomy will achieve biochemical control of their disease (13). The use of other salvage modalities such as cryoablation after failed radiotherapy has been reported. In a large study of quality of life, 72% of patients reported incontinence at a median of 17 months, and two-thirds of patients

reported significant urinary symptoms (14). Rectal injury rates of 2% and incontinence rates between 4% and 8% have been reported. The fistula rate was 3.4% (15). In a large study of salvage cryotherapy, 17% of patients were noted to positive biopsies after treatment (16). Therefore, effective treatment options without significant morbidity in the setting of locally Buspirone HCl recurrent prostate cancer after radiotherapy are limited. The results of low-dose-rate salvage brachytherapy have also been reported. Reports published over 10 years ago [17] and [18] have indicated that while tumor control can be achieved with low-dose-rate salvage brachytherapy in 30–50% of patients, toxicity outcomes were increased possibly related to the use of less sophisticated planning techniques or the selection of less optimal patients based on the presence of baseline symptoms. More recently Chen et al. (7) have described preliminary outcomes of MRI-based partial prostate salvage low-dose-rate brachytherapy in 15 patients with a median followup of 23 months (8–88 months), with no cases of Grade 3 or higher GU complications. Biochemical control was achieved in 73% of patients at 3 years. Aaronson et al.

Aea-HP-1 cross-reacts with antibodies raised to the invertebrate

Aea-HP-1 cross-reacts with antibodies raised to the invertebrate peptide, FMRFamide, presumably because of the common RFamide epitope [4], [30] and [39]. We therefore used a commercially available FMRFamide antibody in an ELISA to monitor HPLC fractions for Aea-HP-1 and any other FMRFamide-like peptides that might be present in the MAGs/SVs extract (Fig. 3). A single peak of ELISA-positive material was eluted from the HPLC column in three consecutive fractions that were also positive for mass ion m/z of 1227.7. All other UV-absorbing APO866 mw fractions gave negative ELISA results, suggesting that Aea-HP-1 was the major peptide component of the extract displaying cross-reactivity to the FMRFamide antibody.

Confocal microscopy of whole mounted MAGs/SVs stained using the same antibody revealed differential distribution of the immunoreactivity with staining largely restricted GSI-IX clinical trial to the MAGs and much

of this being concentrated in the lumen of the anterior region of the gland (Fig. 4). During the course of this investigation it was noticed that dissected MAGs with SVs attached often released gland contents from the SVs by spontaneous contractions of the MAG muscle layer. It was therefore possible to collect MAG secretions into PBS using a pipette and place this material into acidified methanol. Both Aea-HP-1 and Aea-HP-3 were detected in these secretions by MALDI/TOF-MS (m/z, 1227.8 and 1211.8, respectively),

confirming the presence of these peptides as components of the MAG secretions and therefore seminal most fluid. MALDI/TOF-MS was used to analyze methanol extracts for the presence of Aea-HP-1 in the reproductive tract (uterus, spermathecae, bursa copulatrix, oviduct, but not the ovary) of individual virgin and post-mated females obtained by introducing a single female into a cage of 50 males until mating was observed (<5 min). In order to minimize clearance of any transferred Aea-HP-1 from the female reproductive tissues, post-mated females were chilled to 4 °C immediately after copulation. Mass spectrometry failed to detect any evidence for Aea-HP-1 in virgin tissues from ten individual mosquitoes. In contrast, the molecular ions for Aea-HP-1 (m/z, 1227.9) and Aea-HP-3 (m/z, 1211.9) were detected in methanol extracts of tissues from nine out of thirteen post-copulated females. Extracts were also analyzed quantitatively by ELISA using synthetic Aea-HP-1 as a standard and the results were compared to the amount of material found in extracts of MAGs dissected from virgin males. Peptide was detectable in reproductive tissues for ten out of thirteen post-copulated females with a mean value of 102 ± 14 fmol of peptide/insect (mean ± s.e.m., n = 10), whereas the level of peptide in the reproductive tract of all 10 virgin females was below the detection level of the ELISA (<10 fmol).

It is likely that other deep-sea elasmobranchs show similar patte

It is likely that other deep-sea elasmobranchs show similar patterns. Orange roughy is a deepwater demersal species with an almost

global distribution. It inhabits continental slopes and seamounts from 500–1500 m depths. It is slow-growing and reaches ages exceeding 100 years. Natural mortality in adults is low (estimated at 0.045 year−1 off New Zealand), they mature late (at about 30 years), their fecundity is low relative to most teleost species, and adults do not spawn every year. These characteristics make orange roughy much less productive than most shallower-living commercially fished species. Fishing for orange roughy started in New Zealand waters this website in the late 1970s. Subsequently other fisheries developed off southeastern Australia in the late 1980s, in the North Atlantic in 1989, off Namibia in 1995, off Chile in 1998 and in the southwest Indian Ocean (SWIO) in 1999 [80]. New Zealand catches rose steadily through

the 1980s as new populations were discovered, and when the Australian fishery found spawning fish off St Helens Seamount, global catches skyrocketed to over 100,000 t (Fig. 3). Numerous new Ku0059436 fisheries followed in the 1990s and early 2000s, the largest occurring off Namibia and SWIO. The New Zealand fishery has dominated global catches, and is the only one that has persisted over time with total catches of more than a few thousand tonnes. Much of this comes from a restricted area of the Chatham Rise east of the main New Zealand islands [81]. Stocks in most other fishing grounds around New Zealand have declined substantially [82], and mirror the global pattern on a smaller

spatial scale. Serial depletion has occurred in some of the seamount-based fisheries, and a number of areas are now closed (Fig. 4). The Australian fishery was very large between 1989 and 1993 when catch rates of spawning fish on St. Helens Seamount were high, but the stocks were rapidly depleted and quotas were progressively reduced [83]. The St. Helens fishery is now closed completely and Australia declared orange roughy a “threatened species” in 2006. A similar situation occurred off Namibia and Chile [84], [85] and [86], where, despite extensive ZD1839 manufacturer research and precautionary management objectives, catches could not be sustained, and fisheries are now very small or orange roughy are just bycatch. Similarly, in SWIO, large catches were taken for a short time, with uncontrolled increase in effort in the early 2000s with no management on the high seas, then a sharp drop in catches and catch rates [87]. Sissenwine and Mace [18] noted two patterns in these catch histories. In the first, small stocks were fished down rapidly before effective management could be implemented. In the second, with larger stocks, research initially overestimated stock size, often coupled with non-conservative management practises and “fishing-down” phases, which led to excessive depletion.

10–0 26) Similarly, treatment with erlotinib significantly impro

10–0.26). Similarly, treatment with erlotinib significantly improved the objective response rate (83% vs 36%) [27]. In the EURTAC trial, 174 chemonaive patients with EGFR mutation (Exon 19 deletion or L858R mutation) were randomly assigned to erlotinib or platinum-based chemotherapy. The primary-endpoint was progression-free survival which was significantly improved with erlotinib (median 9.7 vs 5.2 months, HR 0.37). The difference in overall survival was not statistically significant, but more than 80% of patients initially treated with chemotherapy subsequently received an EGFR tyrosine kinase inhibitor [28]. Cetuximab is an IgG1 monoclonal antibody directed against the extracellular

domain of the EGFR, which suppresses EGFR-mediated cell signaling by blocking ligand binding to the receptor. As an IgG1 antibody, cetuximab may also kill tumor cells via an immune mechanism: learn more antibody-dependent cellular cytotoxicity. Accordingly, cetuximab works differently from the TKIs. Phase III clinical trials have shown that cetuximab prolongs survival in patients with metastatic colorectal cancer (mCRC) and advanced squamous cell carcinoma of the head and neck. In lung cancer, cetuximab was evaluated in first line

setting. Phase II study of patients with EGFR positive and EGFR-negative advanced NSCLC with Eastern Cooperative Lumacaftor cell line Oncology Group performance status 0–1, assigned to receive cetuximab 400 mg/m2 intravenously (IV) on week 1 followed by weekly doses of cetuximab 250 mg/m2 IV. A cycle was considered as 4 weeks of treatment and therapy was continued until disease progression or intolerable toxicities. The response rate

for all patients (n = 66) was 4.5% (95% CI: 0.9–12.7%) and the stable disease rate was 30.3% (95% CI: 19.6–42.9%). The response rate for patients with EGFR-positive tumors (n = 60) was 5% (95% CI: 1.0–13.9%). The median time to progression for all patients was 2.3 months (95% CI: 2.1–2.6 months) and median survival time was 8.9 months Thalidomide (95% CI: 6.2–12.6 months). Although the response rate with single-agent cetuximab in this heavily pretreated patient population with advanced NSCLC was only 4.5%, the disease control rates and overall survival seem comparable to that of pemetrexed, docetaxel, and erlotinib in similar groups of patients [29]. The phase 3 FLEX (first-line treatment for patients with epidermal growth factor inhibitor [EGFR]-EXpressing advanced NSCLC) trial, of cetuximab combined with vinorelbine/cisplatin, met its primary endpoint of increasing OS when compared with chemotherapy alone; this study enrolled 1125 patients with advanced NSCLC who had evidence of EGFR expression. While median PFS was the same in both treatment groups (4.8 months), median OS was 11.3 months in the group that received cetuximab vs 10.1 months in the group that received chemotherapy alone (p = .044).

No biological or any other meaningful alterations in body weight,

No biological or any other meaningful alterations in body weight, food consumption, or physical features find more were noted. There were no significant dose-related effects in clinical laboratory examinations, and the treatment did not cause gross or microscopic changes in the tissues examined. The occasional presence of neoplasms did not reveal any consistent, dose-related trends in any group. The OECD (2004) derived from this study a NOAEL for chronic oral administration at approximately 2500 mg/kg bw/day. The NOAEL for surface-treated silica in a 6-month

dietary study was at 500 mg/kg bw/day, the only dose tested ( EPA, 2011). The toxic effects of nano- and micron-sized silica particles made from rice husk (and hence biogenic amorphous silica, not SAS) were studied by So et al. (2008). As this study is often discussed in the context of “nanosilica in food” it is nevertheless included in this review. The silica particles were about 30–90 nm

and 0.5–30 μm in size; their purity given as 99.8%. Groups of male and female Balb/c and female C57BL/6 J mice were fed the particles at 1% in the diet or given the diet alone (controls). After feeding for 10 weeks, the blood of three male and three female Balb/c or three female C57BL/6 J mice was tested biochemically and haematologically. Target Selective Inhibitor Library price There was no difference between the groups in the tested parameters except for a higher serum alanine aminotransferase (ALT) value in the Balb/c mice treated with the smaller sized particles as compared to the controls (102.5 vs. 52.50 U/L). It has to be ADP ribosylation factor noted, however, that the high value is well within the normal range of ALT values reported for Balb/C mice in the literature

(40.8 ± 6.7–226 ± 105, Hainfeld et al., 2006). Signs indicative of fatty livers were found histologically in selected animals that received the nano-sized particles, while Si contents of livers in both silica-treated groups were “almost the same”. From the results, it was suggested by the study authors that “the nano-sized silica particle might have a toxic effect on the liver” even though there was no difference on health parameters after feeding a total amount of 140 g silica/kg mouse. Further to the questionable finding of an increase in ALT values in a very small group of animals, amorphous silica from natural origin was used in this study that may have been contaminated with organic impurities or crystalline silica. The findings reported by So et al. (2008), therefore, cannot be used in the assessment of SAS health effects. In a study on mice by Isoda et al. (2011), (30) or 40 mg/kg bw of 70 nm spherical, non-porous silica particles (not specified further), injected intravenously twice per week for 4 weeks induced liver collagenosis and a 3.5-fold increase in hepatic hydroxyproline content, while 60 mg/kg bw of amino- or carboxyl-modified forms of the same particles did not cause liver fibrosis.

The 1st row was used as the medium blank The filled plates were

The 1st row was used as the medium blank. The filled plates were placed in the Bioscreen C followed by a short measurement. The OD from the non-inoculated wells was subtracted from the growth data to minimize the effect of the signal draft. The concentrations of the colony forming units (cfu) were determined by an Abbe counting chamber. On demand, additional 10-fold dilutions were prepared for counting. The honeycomb plates were prepared as described in Section 2.3.1. The incubation temperature was set to 52 °C with interval shaking, changing to medium and slow intensity for 30 s prior and after OD reading. Measurements were taken every 5 min for 32 h. At least two replicate wells were

used in one experiment for the determination buy LEE011 of maximum growth rate for each lignin concentration. Presupposing that the cell concentration increases in sigmoidal shape, different models were used to simulate the bacterial growth curve [3], [15] and [27]. Although these models had the same key parameters, they differed in shape and number of parameters. A logistic, the Gompertz and the Richards and Stannard model were used

in a modified and reparameterised shape as it had been offered by Zwietering et al. [28]. The Baranyi equation [2] was used as a two (μm, λ) and three (μm, λ, v) parametrical model [5] and [9]. • natural logarithm of the quotient of the cell concentration (N) and minimal cell concentration (Nmin) The models were implemented in MATLAB©. A simulated annealing algorithm was used to obtain the statistical global solution with standard properties. The Euclidean CH5424802 in vitro distance was used as optimization criteria. The relationship between a certain concentration of colony forming units per millilitre medium (cfu/ml) and the resulting measurable OD can be used to construct a calibration curve. The calibration curve is used to equate the concentration of the cells at a given time of the experiment. The calibration curve is shown in Fig. 1 and described with a regression of a third order binomial equation in Eq. (1). Using the calibration curve, the values of the measured OD can be directly converted

Wilson disease protein into the microbial concentration. equation(1) cfu/ml=4.3555×1012×OD3+6.9824×10−2×OD2×4.8828×10−4×ODcfu/ml=4.3555×1012×OD3+6.9824×10−2×OD2×4.8828×10−4×OD R2=0.92601R2=0.92601 The general shape of the bacterial growth curve is known and characterized by the lag phase, the exponential growth phase, and the stationary phase. In this study, the simulated annealing algorithm is used and the models are matched to the growth data already published by [15] and [13]. This step is important to check the discrepancy of the optimization results between the key parameters μm and λ compared to the mentioned published results and to each other. Table 1 constitutes a summary about the results of this test. Based on the simulation results it is decided to use the average value of μm and λ of the different models.

Data were collected using a standard protocol chart containing th

Data were collected using a standard protocol chart containing the following information: identification, clinical complaints, physical examination

and results of laboratory tests. Exclusion criteria were the following: other pathologies and infections, treatment with hormones or immunosuppressants, alcoholism, pregnancy and amenorrhea. All procedures were approved by the Ethical Committee of Hospital Universitário Edgard Santos – UFBA, BA. Age-matched normal volunteers (NV) living in the same endemic area (n = 32; 17 men and 15 women) served as controls for the study. NV had no history of cutaneous lesions characteristic of leishmaniasis and tested negative for the intradermal delayed-type hypersensitivity test (DTH) to selleck chemical the Leishmania antigen. When patients were compared with NV we evaluated only the patients age-matched with the controls (n = 32; 17 men and 15 women). These 32 patients did not show any difference in clinical and immunological markers when compared to other patients of the study. For analyses of correlations of PD0325901 nmr hormones with cytokines we used all patients. Clinical evaluation for correlations with hormone or cytokine levels was performed using three parameters: lesion size, time of disease and dose of antimoniate needed to achieve clinical

cure. Lesion size was the measurement of the largest diameter of the largest lesion in cm, time of disease was recorded based on patient information and the dose of antimoniate required was based on the number of treatment cycles received by the patient. Heparinized Dichloromethane dehalogenase peripheral blood was collected between 8 a.m. and 11 a.m., transported on ice to the laboratory and the plasma was stored at −20 °C for measurements of hormone levels. PBMCs were isolated from heparinized venous blood by passage over a Ficoll Hypaque gradient (Sigma–Aldrich). PBMCs were washed three times and resuspended at a concentration of 5 × 106 cells/mL in RPMI

1640 medium (Gibco, NY) supplemented with 2 mM l-glutamine, penicillin (100 U/mL), streptomycin (100 μg/mL) (Gibco, NY) and 10% heat inactivated human AB serum (Sigma–Aldrich). Cells were plated in 24-well tissue culture plates (Costar, Corning Incorporated, NY) at a concentration of 5 × 106 cells/mL and incubated at 37 °C at 5% CO2. Stimulation was performed by adding 10 μg/mL of SLA (soluble Leishmania antigen). The SLA was prepared as described by Carvalho et al. (1985). Briefly, stationary-phase promastigotes of L. amazonensis (MHOMBR86BA-125) were ultrasonicated and centrifuged at 20,000g for 2 h. The supernatant was used at a final concentration of 10 μg/mL. PBMC culture supernatants were harvested at 24, 48 and 96 h after in vitro stimulation and maintained at −20 °C until use.

, 1993), and that the microglia may appear in “clumps” of immunor

, 1993), and that the microglia may appear in “clumps” of immunoreactive membranes in white matter (Perry et al., 1993 and Stichel and Luebbert, 2007). Our study shows that these aggregates are not directly associated with blood vessels and are not clusters of proliferating cells. Macrophages and microglia are known to form multinucleate

giant cells through fusion under a variety of inflammatory conditions (Fendrick et al., 2007, Gasser and Most, 1999 and Suzumura et al., 1999). Whether these cells are aggregates of individual microglia or a single syncytium is not clear from our study, but the appearance of multinucleate giant cells during ageing would represent a significant alteration in microglial phenotype and function. We observed a significant increase in CD11c expression levels, predominantly in the white matter of the cerebellum. CD11c this website is a protein found at high levels on dendritic cells, but is also found on macrophages and microglia under neuroinflammatory conditions (Reichmann et al., 2002 and Remington CAL-101 cost et al., 2007). Increases in CD11c immunoreactivity with age have been reported previously with robust CD11c expression

in the aged white matter and occasional CD11c expression throughout the grey matter (Kaunzner et al., 2010 and Stichel and Luebbert, 2007). These studies describe CD11c positive cells as dendritic cells, as they express DEC-205, MIDC8, MHCII and the co-stimulatory molecules CD80 and CD86. Using immunohistochemistry we did not detect Parvulin DEC-205 or MHCII expression in the aged brain. This discrepancy may be

explained by the superior sensitivity of alternative methods of detection, such as flow cytometry, or by the strain of mice used (Henry et al., 2009). The functional consequence and mechanism underlying increased expression of CD11c in the aged brain is unknown, but increased turnover of myelin with age may be a contributing factor (Ando et al., 2003). It has been shown that engagement of low density lipoprotein receptor 1 (LRP-1) on macrophages results in increased expression of CD11c (Cho et al., 2007 and Gower et al., 2011). Ligands for LRP-1 include low density lipoprotein (Kuchenhoff et al., 1997) and the myelin component MBP-1 (Gaultier et al., 2009). Whether the CD11c + cells in our study are microglia that have taken up myelin components/breakdown products, or infiltrating dendritic cells or macrophages remains to be determined. It is well recognised that the microglia are exquisitely sensitive to neurodegeneration. However, in rodents and primates the extent to which neurodegeneration occurs in the ageing CNS varies considerably from region to region. The substantia nigra (Ma et al., 1999 and Mouton et al., 2010) and cerebellum (Sturrock, 1989 and Woodruff-Pak et al., 2010) exhibit significantly greater age-related neuronal loss than the hippocampus (Calhoun et al.

The concentration of zileuton used in the present study is able t

The concentration of zileuton used in the present study is able to completely block the synthesis of eicosanoids produced by the lipoxygenase pathway (Horizoe et al., 1998; Canetti et al., 2003). Previous observations on the reversal of the inhibitory action of venom and crotoxin by zileuton (Sampaio

et al., 2006; Nunes et al., 2010), as well as the prevention of the inhibitory effect of venom in edema by zileuton observed in the present study, strongly suggest the involvement of eicosanoids from the lipoxygenase pathway in modulating the inhibitory action of venom. We do not yet have unambiguous data on which component or components generated in the lipoxygenase pathway could be involved in the inhibitory effect of the venom. However, this set of results, in conjunction with data obtained from macrophage culture studies and models of acute inflammatory response

(Sampaio Nutlin-3a cell line et al., 2006; Nunes et al., 2010) suggest the involvement of lipoxins in this process. It is known that Cdt venom is able to induce the generation of lipoxins in cultured macrophages (Sampaio et al., 2006) and that the inhibitory activity of this venom on the acute inflammation induced by carrageenan depends on their action on formyl this website peptide receptors, which are related to lipoxins or resolvins (Nunes et al., 2010). Studies have shown that lipoxins may regulate the chronic and the acute inflammatory responses (Kantarci and van Dyke, 2003). Considering that lipoxins need to bind to G-protein coupled receptors, such as

formyl peptides receptors family, to exert their biological actions (Chiang and Serhan, 2006; Ye et al. 2009), the results obtained in the present study with animals pre-treated with Boc2, a specific inhibitor of formyl peptide receptors, reinforce a possible involvement of lipoxins in this inhibitory effect of the Cdt venom on this chronic inflammatory response. To identify which component in the Cdt venom is responsible for the toxin’s inhibitory effect on chronic edema induced by BCG, we found that crotoxin, the major component of the venom and the main toxin responsible for the observed effects in the pathophysiology of Crotalus Nintedanib (BIBF 1120) envenoming, was the only component that presented similar inhibitory results to those observed with crude venom. This result confirms previous studies showing that this toxin interferes with the biological and metabolic activities of macrophages and is responsible for the inhibition of acute inflammatory processes ( Sampaio et al., 2006; Nunes et al., 2010). In conclusion, our results show that C. durissus terrificus venom, and in particular crotoxin, significantly inhibits the chronic paw edema induced by the injection of BCG in mice and suggest that this inhibition may be due to the generation of anti-inflammatory mediator(s) from the lipoxygenase pathway, possibly by the generation of lipoxins.

In 2001, he moved his research program to the University of Misso

In 2001, he moved his research program to the University of Missouri (MU) where he was the Gilbreath-McLorn Professor of Comparative Medicine, Director of the Comparative Medicine Center, Director of the Rat Resource and Research Center, and Chairman of the Veterinary learn more Pathobiology Department. While at MU, he developed

three NIH-funded national animal resource centers which were focused, in large part, on comparative medicine and reproductive cryobiology. In collaboration with other faculty, John was instrumental in establishing the MU Mutant Mouse Resource and Research Center and the Rat Resource and Research Center both of which serve as critical repositories for valuable rodent models. John was also an active participant in establishing a similar resource for swine (National Swine Resource and Research Center). He was responsible for leadership and administration of the core groups involving novel clinical/translational methodologies, translational technologies/resources, and pilot and collaborative translational/clinical

studies. Most recently, Dr. Critser was awarded an R01 component of the Oncofertility U54 program, one of the first funded NIH Roadmap CX-5461 mouse Initiative projects. Dr. Critser contributed greatly to our Society. He served as our Society President, member of Society Committees, on the Editorial Board of Cryobiology, and Chairman of the Society Annual Conference CRYO1997 and Co-Chair of CRYO2004. Dr. Critser was also a member of many other professional societies and editorial review boards; he was continuously funded by the NIH for over 20 years; and was the past chair of the NIH National Center for Research Resources (NCRR) Comparative Medicine Study Section. Dr. Critser was a well-respected scholar and researcher in the fields of cryobiology, comparative medicine and reproductive biology. He authored or Methocarbamol co-authored over 190 publications. His vision and unique ability to forge fruitful and lasting collaborations among individuals with diverse expertise from all over the world were among his notable strengths.

More important to him than any of these other accomplishments, Dr. Critser was proud and passionate about training graduate students and post-doctoral fellows. He mentored more than 30 graduate students and 20 postdoctoral fellows, many of whom are now in professional and leadership roles in the areas of cryobiology, comparative medicine, reproductive biology, molecular biology, engineering, medicine and veterinary medicine. He not only nurtured them during their training but also continued to mentor, help, collaborate and support them as they matured professionally. John Critser was a devoted cryobiologist who contributed significantly to our field. While his career ended abruptly and far too soon, his contributions were reflective of someone with decades more time among us.