Reviewing fair subject selection considerations for the unique case of post sequelae COVID-19 translational studies.

Fair inclusion of research subjects is necessary to ensure that post-acute sequelae COVID-19 (PASC) research results benefit all members of society. Scientists should conduct research on a broad sample of individuals who represent clinically relevant factors influencing a disease. Without demographic diversity and sociological and environmental variability, research outputs are less likely to apply to different populations and would thus increase health disparities. The goal of this narrative literature review and ethical analysis is to apply fair selection criteria to PASC research studies. We briefly highlight the importance of fair subject selection in translational research and then identify features of PASC, as well as PASC research, that hinder fair inclusion of research participants. We will demonstrate that determining an adequate and representative sample is not simply a matter of ensuring greater diversity; rather, fairness requires a broader evaluation of risks, burdens, and benefits specific to underrepresented populations. We provide recommendations to ensure fair subject selection in PASC research and promote translation toward positive health outcomes for all individuals, including the most vulnerable.

Reimagining IRB review to incorporate a clear and convincing standard of evidence.

This commentary is a critical response to the article written by David Resnik regarding the use of a standard of evidence for Institutional Review Board (IRB) decision making. Resnik suggests that IRBs should not only base decisions on evidence, but that this evidence should be sufficient to ensure a "clear and convincing" standard similar to that used by juries for legal proceedings. We agree that the increased use of evidence to meet this standard would be ideal since this provides clear guidance and could allow for a more transparent IRB review. However, to effectively meet this standard, significant modification would be required for researchers as well as for IRBs' processes. First, researchers would be required to identify, understand and include appropriate scientific and ethics evidence in support of their protocol. IRB members and IRB professionals would need to discuss the importance, value, and significance of evidence in order to come to a collective decision regarding each protocol. Such responsibilities are justifiable and could bring much needed rigor and transparency to the system but they would require time, training, research, and education. While Resnik's suggestion seems to incorporate a small change with respect to a standard, in application it would actually require a novel system.

Changes in morphology of retinal ganglion cells with eccentricity in retinal degeneration.

Ganglion cells are the output neurons of the retina and are known to remodel during the subtle plasticity changes that occur following the death of photoreceptors in inherited retinal degeneration. We examine the influence of retinal eccentricity on anatomical remodelling and ganglion cell morphology well after photoreceptor loss. Rd1 mice that have a mutation in the ß subunit of phosphodiesterase 6 were used as a model of retinal degeneration and gross remodelling events were examined by processing serial sections for immunocytochemistry. Retinal wholemounts from rd1-Thy1 and control Thy1 mice that contained a fluorescent protein labelling a subset of ganglion cells were processed for immunohistochemistry at 11 months of age. Ganglion cells were classified based on their soma size, dendritic field size and dendritic branching pattern and their dendritic fields were analysed for their length, area and quantity of branching points. Overall, more remodelling was found in the central compared with the peripheral retina. In addition, the size and complexity of A2, B1, C1 and D type ganglion cells located in the central region of the retina decreased. We propose that the changes in ganglion cell morphology are correlated with remodelling events in these regions and impact the function of retinal circuitry in the degenerated retina.

Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features.

OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.

Assessing treatment progress of individual patients using expected treatment response models.

The dosage model provides a normative estimate of the overall pattern of patient improvement in psychotherapy. The phase model further specifies patterns of change in the domains of subjective well-being, symptom remediation, and functioning. The expected treatment response (ETR) approach uses patient characteristics to predict an expected path of progress for each patient. With repeated measures of mental health status, the treatment progress of an individual patient can be assessed against the patient's ETR to support decisions that would enhance the quality of a clinical service while it is being delivered.

Loss of p53 in benzene-induced thymic lymphomas in p53+/- mice: evidence of chromosomal recombination.

The purpose of this study was to examine the role of chromosomal recombination in mediating p53 loss in benzene-induced thymic lymphomas in C57BL/6-Trp53 haploinsufficient (N5) mice (p53+/- mice). We characterized loss of heterozygosity (LOH) on chromosome 11 using seven microsatellite markers in 27 benzene-induced and 6 spontaneous thymic lymphomas. Eleven patterns of LOH were found between the induced and spontaneous tumors, with only one pattern being in common between the tumor groups. Nearly 90% (24 of 27) of benzene-induced tumors exhibited loss of the functional p53 allele locus, and 83% (20 of 24) of these tumors retained two copies of the disrupted p53 allele. The results indicate that benzene induces a high frequency of LOH on chromosome 11 in p53+/- mice, likely mediated by aberrant chromosomal recombination.

Early onset baldness and prostate cancer risk.

Prostatic carcinoma is the leading cancer among American men, yet few risk factors have been established. Although increased androgen levels have long been associated with both prostatic carcinoma and baldness, to date no studies have shown an association between hair patterning and prostate cancer risk. A lack of standardized instruments to assess baldness or the assessment of hair patterning during uninformative periods of time may have precluded the ability of previous studies to detect an association. We hypothesized that baldness, specifically vertex baldness, should be assessed using standardized instruments and during early adulthood if an association with prostate cancer risk is to be found. To test this hypothesis, we included identical items related to hair patterning in surveys that were administered in two distinct prostate cancer case-control studies (Duke-based study, n = 149; 78 cases; 71 controls and community-based study, n = 130; 56 cases; 74 controls). In each, participants were provided with an illustration of the Hamilton Scale of Baldness and asked to select the diagrams that best represented their hair patterning at age 30 and again at age 40. From these data, the following five categories were created and compared: not bald (referent group); vertex bald early onset (by age 30); vertex bald later onset (by age 40); frontal bald early onset (by age 30); frontal bald later onset (by age 40); and frontal (at age 30) to vertex bald (at age 40). Separate analyses of the two studies are consistent and suggest an association between vertex baldness and prostate cancer [vertex bald early onset odds ratios, 2.44 [confidence interval (CI), 0.57-10.46)] and 2.11 (CI, 0.66-6.73), respectively; vertex bald later onset odds ratios, 2.10 (CI, 0.63-7.00) and 1.37 (CI, 0.47-4.06), respectively]. Although statistical significance was not achieved in either one of these studies, the concordance between the data suggests a need for future studies to determine whether early onset vertex baldness serves as a novel biomarker for prostate cancer and whether androgen production, metabolism, or receptor status differs among these men when compared to those who exhibit other types of hair patterning.

Issues surrounding record keeping in district nursing practice.

This article examines some aspects of nursing documentation following the publication of the document 'Guidelines for Records and Record Keeping' (UKCC, 1998). The importance of nursing documentation in patient care, in guiding practice and in providing information for members of the interprofessional healthcare team is highlighted. Record keeping forms an important part of the clinical governance initiative in terms of quality improvement and risk management. The issues surrounding the legal requirements of record keeping in district nursing practice are discussed. Suggestions are made for assessing the quality of nursing documentation by audit and research, in order to establish the suitability of using the present systems in the community setting.

Anthropometric risk factors for prostate cancer.

Cancer of the prostate is the leading cancer among American men, yet few risk factors are known. Anthropometry may help uncover potential risk factors for prostate cancer, since fat distribution, skeletal structure, and musculature may differ between men with this hormonally linked cancer and those without it. A case-control study was undertaken to determine whether anthropometric differences exist between prostate cancer cases and controls and whether such differences are associated with specific hormonal profiles. The study accrued 315 men stratified for race, age, and case/control status. Weight, height (sitting/standing), skinfold thicknesses (triceps, biceps, subscapular, suprailiac, thigh), circumferences (midarm, waist, hip, thigh), breadths (elbow, biacromial, biiliac), hormonal levels (total and free testosterone, dihydrotestosterone, sex hormone-binding globulin), bone density, and body composition were measured. Measures of upper body robustness [i.e., biacromial breadth-to-height ratio (p = 0.02) and biacromial (p = 0.05) and bideltoid (p = 0.04) breadths] were greater among controls. Strong negative associations were found uniformly between sex hormone-binding globulin levels and measures of body adiposity and musculature. Data show that prostate cancer cases exhibit a propensity toward a slight upper body skeleton, which may in itself serve as a risk factor or provide a benchmark of past nutritional and/or hormonal status and help elucidate the etiology of this disease.

Vesical endometriosis: report of two cases and review of the literature.

Endometriosis is a common gynecologic disease in which endometrial tissue is deposited outside the normal confines of the uterine cavity. In rare instances, endometriosis involves the urinary tract, with the bladder the most frequent organ affected. Classic presenting symptoms include cyclic irritative voiding symptoms and suprapubic discomfort with or without hematuria. Both medical and surgical management have been advocated, but surgical extirpation is probably more efficacious. Two cases of endometriosis involving the the bladder are presented and contrasted in terms of pathophysiology. Contemporary management of this condition is reviewed, and guidelines for diagnosis and treatment are proposed.

Pheochromocytoma of urinary bladder: contemporary methods of diagnosis and treatment options.

Two patients with vesical pheochromocytoma are presented with a review of the literature. Imaging modalities for localizing extra-adrenal pheochromocytomas are reviewed with an overview of the commonly accepted treatment options. Successful treatment of this lesion requires a high index of suspicion based upon the patient's symptom complex, allowing preoperative preparation prior to surgical manipulation.

Sclerosing lipogranulomatosis: a case report of scrotal injection of automobile transmission fluid and literature review of subcutaneous injection of oils.

For nearly a century, physicians and laypersons have attempted to repair, reconstruct, and embellish the human body in numerous ways by injecting various oils beneath the skin. Soon after Gersuny's first reported subcutaneous injection of oil, the local and systemic complications became apparent. Despite this, the practice of oil injections continues. "Medical grade" silicone injection was investigated in the 1960s to 1980s with varied success and complications. While few physicians practice oil injection therapy, some laypersons continue to subject themselves or their clients to the risk of the disfiguring complications of sclerosing lipogranulomata. Accidental high-pressure injection injury of liquids, so-called grease gun injuries, continues to provide a therapeutic challenge for the hand surgeon. Our case of a man who injected automobile transmission fluid into his scrotum illustrates the classical course and proper management of sclerosing lipogranulomata. A subcutaneous inflammatory and fibrosing reaction occurred with regional lymphadenopathy. The need for complete excision of all involved tissue to treat the condition successfully is illustrated. This case also illustrates the tendency of patients to conceal from their doctors the history of self-injection of foreign bodies. In cases of self-injection, psychological counseling might certainly be appropriate.

Successful management of bilateral xanthogranulomatous pyelonephritis by bilateral partial nephrectomy.

Bilateral xanthogranulomatous pyelonephritis is a rare condition with 7 previously reported cases, all of which required dialysis and/or resulted in death of the patient. We report a case in which bilateral partial nephrectomy was performed successfully for bilateral xanthogranulomatous pyelonephritis. The etiology, symptomatology, radiographic findings and treatment of this rare inflammatory condition are discussed with a brief review of the previously reported cases.

Squamous cell carcinoma of the prostate: 2 cases of a rare malignancy and review of the literature.

Primary squamous cell carcinoma of the prostate is an extremely uncommon malignancy, accounting for less than 1% of all prostatic cancers. We report on 2 patients with primary squamous cell carcinoma of the prostate: 1 with organ-confined disease and 1 with metastatic disease. Both patients presented with urinary obstructive symptoms and carcinoma was not suspected on digital rectal examination. Serum acid phosphatase and prostate specific antigen levels were normal. From a review of the literature and our 2 cases it is apparent that squamous cell carcinoma of the prostate is biologically more aggressive than adenocarcinoma.

Accuracy in staging of renal cell carcinoma involving vena cava.

Accurate preoperative staging of renal cell carcinoma is necessary to determine patient prognosis and surgical approach, particularly when tumor thrombus invades the vena cava. The pathologically-confirmed tumor stage was compared with the radiographic preoperative stage in 44 patients undergoing surgery for renal cell carcinoma invading the vena cava (T3cNxMx). Nine patients (20%) were upstaged as the result of extracapsular tumor extension. Twelve patients (27%) were upstaged due to unrecognized regional lymphadenopathy, and 1 patient was downstaged. Only 1 patient was upstaged as the result of unrecognized metastases. The level of tumor thrombus extension for surgical approach was accurately determined in all but 2 patients. Overall, 15 patients (34%) were upstaged as a result of pathologic studies, 28 patients (64%) were correctly staged, and 1 patient was downstaged. Radiographic staging of extracapsular tumor extension and regional lymphadenopathy is unreliable, but current radiographic techniques delineate the level of thrombus extension for surgical approach with high accuracy.