Comparing impacts of the COVID-19 pandemic on training of public health Specialty Registrars starting before or after its onset.

Objectives: To capture and compare the differences in experiences of public health Specialty Registrars who commenced training prior to the COVID-19 pandemic (pre-pandemic Registrars) and those who commenced training during the pandemic (post-pandemic Registrars). Study design: This is a mixed methods study comprising a cross-sectional survey and participatory action research. Methods: A questionnaire of 10 open and 5 closed questions exploring participants experience of training during the pandemic was sent to East Midlands Specialty Registrars. Thematic analysis and double coding were undertaken, coded based on pre- or post-pandemic Registrar status. Participatory action research was then undertaken in 2 rounds with 2 groups, based on pre/post-pandemic status to consolidate themes. Results: The survey was completed by 17 Registrars (8 pre-pandemic, and 9 post-pandemic) and 19 Registrars took part in participatory action research. The findings showed pre-pandemic Registrars noted the importance of negative impacts on their mental health whilst post-pandemic Registrars were more positive and felt well supported in their training. Conclusions: There is a stark difference in the impact of the pandemic for Registrars who started training before compared to during the pandemic. The training programme was not resilient to the impact of the pandemic. Robustness could be increased by encouraging early leadership experience and providing wellbeing support, particularly for post pandemic Registrars now and in future.

The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery.

UNLABELLED: Vital healthcare resources are devoted to caring for patients with prolonged hospitalization after routine, moderate-risk surgery. Despite the significant cost, little is known about the overall incidence and pattern of complications in these patients. Four hundred thirty-eight patients undergoing a diverse group of routine, moderate-risk, elective surgical procedures were enrolled into a prospective, blinded, cohort study. Complications were assessed using a postoperative morbidity survey. The main outcome was postoperative complication, defined as either in-hospital death or prolonged postoperative hospitalization (> 7 days). The mortality rate was 1.6%. Postoperative complications occurred in 118 patients (27% [95% CI 23-31]). Complications frequently observed in these patients included: gastrointestinal 51% (42-60), pulmonary 25% (17-33), renal 21% (14-28), and infectious 13% (7-19). Most complications were not directly related to the type/site of surgery. Indices of tissue trauma (blood loss [P < 0.001], surgical duration [P = 0.001]) and tissue perfusion (arterial base deficit [P = 0.008], gastric pHi [P = 0.02]) were the strongest intraoperative predictors of complications. Despite a low mortality rate, we found that complications after routine, moderate-risk, elective surgery are common and involve multiple organ systems. Our 9-point survey can be used by healthcare providers and payers to characterize post-operative morbidity in their respective settings. IMPLICATIONS: Little is known about the overall incidence and pattern of complications in patients with prolonged hospitalization after routine, elective surgery. We prospectively assessed these complications using a novel postoperative morbidity survey. The postoperative morbidity survey can be used in future clinical outcome trials, as well as in routine hospital-based quality assurance.

The effects of hyperoxic and hypercarbic gases on tumour blood flow.

Carbogen (95% O2 and 5% CO2) has been used in preference to 100% oxygen (O2) as a radiosensitizer, because it is believed that CO2 blocks O2-induced vasoconstriction. However, recent work suggests that both normal and tumour arterioles of dorsal flap window chambers exhibit the opposite: no vasoconstriction vs constriction for O2 vs carbogen breathing respectively. We hypothesized that CO2 content might cause vasoconstriction and investigated the effects of three O2-CO2 breathing mixtures on tumour arteriolar diameter (TAD) and blood flow (TBF). Fischer 344 rats with R3230Ac tumours transplanted into window chambers breathed either 1%, 5%, or 10% CO2 + O2. Intravital microscopy and laser Doppler flowmetry were used to measure TAD and TBF respectively. Animals breathing 1% CO2 had increased mean arterial pressure (MAP), no change in heart rate (HR), transient reduction in TAD and no change in TBF. Rats breathing 5% CO2 (carbogen) had transiently increased MAP, decreased HR, reduced TAD and a sustained 25% TBF decrease. Animals exposed to 10% CO2 experienced a transient decrease in MAP, no HR change, reduced TAD and a 30-40% transient TBF decrease. The effects on MAP, HR, TAD and TBF were not CO2 dose-dependent, suggesting that complex physiologic mechanisms are involved. Nevertheless, when > or = 5% CO2 was breathed, there was clear vasoconstriction and TBF reduction in this model. This suggests that the effects of hypercarbic gases on TBF are site-dependent and that use of carbogen as a radiosensitizer may be counterproductive in certain situations.

Preoperative oral naproxen for pain relief after day-case laparoscopic sterilization.

Analgesia with preoperative naproxen after laparoscopic sterilization was assessed in a prospective, double-blind, randomized study of 80 women; 42 women received oral naproxen 1 g, approximately 90 min before surgery, and 38 received placebo. Preoperative naproxen did not significantly influence postoperative pain scores, but was associated with a reduction in parenteral opioid administration (P = 0.04).

Structure of the 5' flanking region of class 3 aldehyde dehydrogenase in the rat.

Class 3 aldehyde dehydrogenase (ALDH-3) is induced by exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and during chemical carcinogenesis. These inductions as well as the basal expression of ALDH-3 vary significantly in different organs. In order to identify DNA elements controlling ALDH-3 expression, we have cloned and analyzed approximately 5.5 kb of the 5' flanking region of the ALDH-3 gene. Deletion analysis showed that the 5' flanking region contains at least three functional domains: a strong promoter proximal to the transcription start site, inhibitory regions upstream of the promoter, and TCDD-responsive enhancers. The TCDD-responsive enhancers in the ALDH-3 gene were functionally similar to xenobiotic responsive elements in the cytochrome P450IA1 gene. These results indicate that transcription of the ALDH-3 gene is controlled by cooperation of at least three functional domains.

Organization and characterization of the rat class 3 aldehyde dehydrogenase gene.

Expression of class 3 aldehyde dehydrogenase (ALDH-3) is constitutive or inducible, depending on the tissue. ALDH-3 induction occurs both during neoplastic development and after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to study the regulation of ALDH-3 gene expression, ALDH-3 genomic sequences have been obtained from normal rat genomic DNA. Two overlapping genomic fragments (ALDH-UTR-1 and ALDH-NL2) contain the entire ALDH-3 gene along with considerable 5'- and 3'-flanking sequences. The rat ALDH-3 gene spans approximately 9 kilobases in length and consists of eleven exons; ten coding and one 5'-noncoding. The region 5' to exon one contains several putative transcription factor binding elements which may be important in the TCDD inducibility of this gene. These include a xenobiotic response element (XRE), a drug response element (DRE), LAP and Ap1 binding sites, and one Sp1 site. There are considerable differences in organization between the rat and human class 3 ALDH genes. Primer extension and RNase protection analysis indicate that both basal and TCDD-inducible expression of the ALDH-3 gene utilize the same multiple transcription start sites.

Efficient high repetition rate synchronous amplification of a passively mode-locked femtosecond dye laser.

We demonstrate reliable operation of a stable synchronously pumped dye amplifier for femtosecond pulses from a passively mode-locked dye laser. Conversion efficiencies of 8% are obtained with output powers of 40 mW and 50-fs pulse widths at repetition rates of up to 10 kHz with pulse energy stability of 3% rms. Synchronization is achieved by driving the frequency-modulated mode-locked seed oscillator for the regenerative amplifier pump laser directly from the dye laser oscillator. Low timing jitter between the dye oscillator and seed laser of less than 1 ps leads to efficient amplification and low amplified spontaneous emission (1%) from the amplifier.

Phenobarbital-inducible aldehyde dehydrogenase in the rat. cDNA sequence and regulation of the mRNA by phenobarbital in responsive rats.

In the rat, a cytosolic isozyme of aldehyde dehydrogenase, designated ALDH-PB, can be induced in the liver by administration of phenobarbital (PB). ALDH-PB activity and mRNA are induced in Long-Evans rats that possess a responsive (R) allele but are not induced in homozygous nonresponsive rats (rr), although the rr genotype is competent to induce other PB-responsive mRNAs. ALDH-PB mRNA is expressed in the basal state (without PB administration) in hepatic tissue in both RR and rr genotypes. We report the complete nucleotide sequence of the rat ALDH-PB mRNA. The protein encoded by the ALDH-PB mRNA is 501 amino acids in length and has a predicted molecular mass of 54,540 daltons. The amino acid sequence predicted from the mRNA demonstrates a strong conservation between the rat ALDH-PB and the human cytosolic aldehyde dehydrogenase hALDH-1. We demonstrate the ALDH-PB, cytochrome P-450b, cytochrome P-450e, and glutathione S-transferase Ya subunit mRNA levels in the liver are altered noncoordinately by administration of PB in RR and rr genotypes. The strikingly different responses to PB administration between the various mRNA species in each of the genotypes suggest that the regulation of specific gene expression by PB may involve multiple pathways.

Human gamma-glutamyl transpeptidase cDNA: comparison of hepatoma and kidney mRNA in the human and rat.

gamma-Glutamyl transpeptidase (GGT) is a glutathione-metabolizing enzyme that has been extensively studied in relation to hepatocarcinogenesis. Using a cDNA for rat kidney GGT as a probe, we have isolated a full-length cDNA for human GGT from a hepatoma cell-line library. Nucleotide sequence analysis of the clone revealed a 2326-bp insert that includes a 5'-untranslated region of 487 nucleotides (nt), an open reading frame (ORF) of 1707 nt, and a 3'-untranslated region of 132 nt. The ORF encodes a protein with an amino acid sequence that is highly similar to that of the rat GGT precursor peptide, with an overall identity of 79%. The cDNA clone was used to probe Northern blots of hepatoma and kidney RNA from both human and rat. In both species, the GGT mRNA is longer in hepatoma than in kidney. In addition, the human mRNAs were longer than their counterparts in the rat. None of three human hepatocellular carcinomas examined showed a marked elevation in GGT mRNA levels relative to surrounding liver tissue.

Differential gene expression in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Noncoordinate regulation of a TCDD-induced aldehyde dehydrogenase and cytochrome P-450c in the rat.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) regulates the transcription of a specific subset of genes through a receptor-mediated mechanism. We have isolated a cDNA to a TCDD-inducible rat liver aldehyde dehydrogenase and have shown that its induction by TCDD differs from that of another TCDD-induced gene, cytochrome P-450c, with regard to dose-response relationship, induction kinetics, and tissue specificity. At least a 10-fold higher dose of TCDD was required for half-maximal induction of TCDD-inducible rat liver aldehyde dehydrogenase in rat liver than the dose that half-maximally induced cytochrome P-450c. Further, the kinetics of induction of TCDD-inducible rat liver aldehyde dehydrogenase by TCDD in rat liver was delayed compared with that of cytochrome P-450c. Striking discrepancies were found in the capacity of various organs to induce both TCDD-inducible rat liver aldehyde dehydrogenase and cytochrome P-450c in a coordinated manner in response to TCDD. Organs that were able to evoke one of these responses to TCDD were not necessarily able to evoke coordinately the other response. The capacity of an organ to exhibit either of these two responses to TCDD did not correlate stringently with reported Ah receptor abundance. Our data suggest that TCDD can modulate the expression of specific genes in different ways and that regulatory pathways in addition to the classically defined Ah receptor may be involved.