The psychosocial and emotional experiences of cancer patients during the COVID-19 pandemic: A systematic review.

BACKGROUND: COVID-19 was declared a pandemic by the World Health Organization on March 11th, 2020. Global social lockdowns were instigated to reduce spread and prevent health-services from becoming overwhelmed. People having treatment for cancer are known to have heightened psychological/emotional burden. The combined impact of managing pandemic regulations alongside this may present additional burden. The purpose of this systematic review is to examine current evidence of the psychological and emotional impact of COVID-19 on people with cancer, early in the pandemic. METHODS: Five electronic databases were searched (Embase, Global Health, HMIC, PsychINFO, CINAHL) from September 2019 to October 2021. Qualitative, quantitative and mixed-method primary research studies exploring emotional and psychological impacts of COVID-19 on cancer patients, limited to English language, were included. Quality appraisal was conducted using the MMAT. RESULTS: Fifty-one papers, with 27,356 people from 21 countries treated for cancer, were included. 43 studies were quantitative with a survey method approach, six studies qualitative and four used a mixed methods design. MMAT score was mostly two or three. Four themes were identified: Emotional aspects and Quality of Life; Psychosocial aspects; Impact of COVID-19 on self; Impact of COVID-19 on cancer, with themes overlapping. CONCLUSION: Whilst emotional/psychological impacts such as anxiety, isolation, employment fears, and uncertainty about the future were potentially universal concerns early in the pandemic, they may have been particularly acute for people living with cancer and represent complex, overlapping factors. As COVID-19 continues to impact health-services and society, it is important to focus on any ongoing impact to the experience of cancer patients. Most of the studies reviewed used tools that do not provide deeper understanding of how and why emotional states of people with cancer were affected. Further qualitative work may reveal patterns of what was unique to cancer patients during the pandemic, compared to general populations.

Real-time high dynamic range laser scanning microscopy.

In conventional confocal/multiphoton fluorescence microscopy, images are typically acquired under ideal settings and after extensive optimization of parameters for a given structure or feature, often resulting in information loss from other image attributes. To overcome the problem of selective data display, we developed a new method that extends the imaging dynamic range in optical microscopy and improves the signal-to-noise ratio. Here we demonstrate how real-time and sequential high dynamic range microscopy facilitates automated three-dimensional neural segmentation. We address reconstruction and segmentation performance on samples with different size, anatomy and complexity. Finally, in vivo real-time high dynamic range imaging is also demonstrated, making the technique particularly relevant for longitudinal imaging in the presence of physiological motion and/or for quantification of in vivo fast tracer kinetics during functional imaging.

Genetic variation in the structural pattern of osteoclast activity during post-natal growth of mouse femora.

While the spatial activity of osteoblasts has been associated with modeling of bones during development, few studies have examined if variation in the spatial activity of osteoclasts also contributes to the morphogenesis of skeletal tissues. We examined this question by histomorphometric analysis and reconstructing the three-dimensional spatial distribution of osteoclasts in the femora of three inbred strains of male mice (A/J, C57BL/6J [B6], and C3H/HeJ [C3H]) that have differing skeletal, structural, and material properties. Our data show that total osteoclast surface area and osteoclast numbers are related to the overall bone density, but not related to the development of bone diameter or overall cortical area. The analysis of the spatial distribution of the osteoclasts showed that the asymmetrical mid-diaphyseal distribution of osteoclasts in A/J and B6 compared to the more uniform distribution of these cells around the circumference in the C3H mice was consistent with the more ellipsoid shape of A/J and B6 femora compared to the more circular mid-diaphyseal shape of the femora in the C3H mice. The statistically 2- to 3-fold fewer cells on the periosteal surface in the C3H compared to either the B6 or A/J mice is also consistent with the greater cortical thickness that is seen for the C3H mice compared to either B6 or A/J strains. In vitro studies of osteoclastogenesis and the expression of numerous phenotypic properties of osteoclasts prepared from the three strains of mice showed that A/J and B6 mice developed statistically greater numbers of tartrate resistant acid phosphatase (TRAP) positive cells and expressed statistically higher levels of multiple mRNAs that are unique to differentiated osteoclasts than those isolated from the C3H strain. In summary, the 3D reconstructions and histomorphometric analysis suggest that genetic differences lead to spatial variation in the distribution of osteoclasts. These variations in spatial distribution of osteoclasts in turn contribute in part to the development of the structural variations of the femora that are seen in the three strains of mice. In vitro studies suggest that intrinsic genetic variation in osteoclastogenesis and their phenotypic expression may contribute to the differences in their functional activities that give rise to the unique spatial distributions of these cells in bones.

Retrospective analysis of 49 cases of brain abscess and review of the literature.

The case records of 49 patients discharged from St George's Hospital, London, between December 2000 and March 2004 with the diagnosis of brain abscess were reviewed in order to document the epidemiology, causes, treatment, and prognostic factors associated with brain abscess. Brain abscess occurred at all ages, more frequently in men than in women. Headache and altered mental status were common presenting symptoms. The frontal lobe was the most common site. Streptococcal infection was seen most commonly, but staphylococcal infection predominated in cases following neurosurgery. Computed tomography provided sufficient diagnostic information in most cases. All but five patients had early surgical drainage. Cefotaxime and metronidazole were used most often for empirical therapy. Thirty-nine patients recovered fully or had minimal incapacity. Five patients died. Patients with underlying cranial neoplasms or medical conditions had a worse outcome than those with a contiguous focus of infection or post-traumatic abscess. Changes in disease pattern were determined by comparison to a literature review. A PubMed search of the literature using the keywords "brain abscess" was undertaken, and identified papers and relevant citations were reviewed. Compared to earlier series, there was a marked decrease in the number of cases of brain abscess secondary to otitis media and congenital heart disease. There was an increase in the number of cases of brain abscess secondary to neurosurgery and trauma. Changes in the epidemiology of predisposing conditions for brain abscess are associated with changes in the patient population and causative organisms. Though still a potentially fatal infection, there have been recent improvements in diagnosis, treatment, and outcome.

Aneurysmal bone cyst of the spine.

The authors present the case of an 11-year-old boy with a painful, rapidly expanding lesion in the posterior triangle of the neck. There was no history of cervical trauma. Computerized tomography of the neck revealed a unicameral (single-chambered) aneurysmal bone cyst involving the C3 vertebra. Treatment was by open resection and curettage; no recurrence was seen at six months. We discuss the natural history, differential diagnosis, radiographic appearance and treatment modalities for this unusual, benign, expanding, osteolytic lesion containing blood-filled cystic cavities.

Implementation of random set-up errors in Monte Carlo calculated dynamic IMRT treatment plans.

The fluence-convolution method for incorporating random set-up errors (RSE) into the Monte Carlo treatment planning dose calculations was previously proposed by Beckham et al, and it was validated for open field radiotherapy treatments. This study confirms the applicability of the fluence-convolution method for dynamic intensity modulated radiotherapy (IMRT) dose calculations and evaluates the impact of set-up uncertainties on a clinical IMRT dose distribution. BEAMnrc and DOSXYZnrc codes were used for Monte Carlo calculations. A sliding window IMRT delivery was simulated using a dynamic multi-leaf collimator (DMLC) transport model developed by Keall et al. The dose distributions were benchmarked for dynamic IMRT fields using extended dose range (EDR) film, accumulating the dose from 16 subsequent fractions shifted randomly. Agreement of calculated and measured relative dose values was well within statistical uncertainty. A clinical seven field sliding window IMRT head and neck treatment was then simulated and the effects of random set-up errors (standard deviation of 2 mm) were evaluated. The dose-volume histograms calculated in the PTV with and without corrections for RSE showed only small differences indicating a reduction of the volume of high dose region due to set-up errors. As well, it showed that adequate coverage of the PTV was maintained when RSE was incorporated. Slice-by-slice comparison of the dose distributions revealed differences of up to 5.6%. The incorporation of set-up errors altered the position of the hot spot in the plan. This work demonstrated validity of implementation of the fluence-convolution method to dynamic IMRT Monte Carlo dose calculations. It also showed that accounting for the set-up errors could be essential for correct identification of the value and position of the hot spot.

Chaotic electron diffusion through stochastic webs enhances current flow in superlattices.

Understanding how complex systems respond to change is of fundamental importance in the natural sciences. There is particular interest in systems whose classical newtonian motion becomes chaotic as an applied perturbation grows. The transition to chaos usually occurs by the gradual destruction of stable orbits in parameter space, in accordance with the Kolmogorov-Arnold-Moser (KAM) theorem--a cornerstone of nonlinear dynamics that explains, for example, gaps in the asteroid belt. By contrast, 'non-KAM' chaos switches on and off abruptly at critical values of the perturbation frequency. This type of dynamics has wide-ranging implications in the theory of plasma physics, tokamak fusion, turbulence, ion traps, and quasicrystals. Here we realize non-KAM chaos experimentally by exploiting the quantum properties of electrons in the periodic potential of a semiconductor superlattice with an applied voltage and magnetic field. The onset of chaos at discrete voltages is observed as a large increase in the current flow due to the creation of unbound electron orbits, which propagate through intricate web patterns in phase space. Non-KAM chaos therefore provides a mechanism for controlling the electrical conductivity of a condensed matter device: its extreme sensitivity could find applications in quantum electronics and photonics.

"Anorexia saved my life": coincidental anorexia nervosa and cerebral meningioma.

OBJECTIVE: We report on a 13-year-old girl with coincidental occult intracranial tumor and early-onset anorexia nervosa. METHOD: The cerebral meningioma was discovered fortuitously as the result of a research project using SPECT imaging to locate a neurobiological substrate in patients with anorexia nervosa. Without SPECT, the meningioma would have remained undiagnosed until it had become symptomatic. The two conditions appear to have been completely unrelated. RESULTS AND DISCUSSION: The case highlights two important points. First, intracranial pathology should also be considered however certain is the diagnosis of early-onset anorexia nervosa. Second, neuroimaging plays an important part in diagnosing early-onset anorexia nervosa, both from a clinical and a research prospective.

Gliomatosis cerebri: pitfalls in diagnosis.

We report two young patients with obscure presentations of gliomatosis cerebri. Initial CT scanning was inconclusive and in one case showed intraventricular haemorrhage, a feature not previously described. Magnetic resonance imaging was required to show the lesions with greater definition; however, in both cases, a biopsy was needed to confirm the diagnosis.

Regulation of proximal tubule sodium/hydrogen antiporter with chronic volume contraction.

We developed a model of volume contraction in rabbits by using a furosemide/low-salt diet to follow changes, if any, in proximal tubule Na+/H+ exchanger 3 (NHE3) mRNA and brush-border protein. The rabbits' plasma renin, aldosterone, and urine sodium content confirmed the volume-contracted state. RNase protection assays demonstrated increases in treated-animal NHE3 mRNA as a percentage of control with 172 +/- 23, 154 +/- 15, 153 +/- 14, and 141 +/- 7 (SE) % (P < 0.05) at 1, 5, 10, and 31 days, respectively. Western analysis of brush-border membrane with NHE3 antibody revealed increased immunoreactivity in treated animals as a percentage of control with 120 +/- 30, 190 +/- 59, 307 +/- 72, and 427 +/- 41% (P < 0.05) at 1, 5, 10, and 31 days, respectively. There was no significant difference in serum potassium, bicarbonate, and cortisol in control vs. experimental animals. These data suggest that there is chronic upregulation of NHE3 in the volume-contracted state.

Molecular staging of colorectal cancer: K-ras mutation analysis of lymph nodes upstages Dukes B patients.

PURPOSE: Multiple attempts have been made to improve the clinical/pathologic staging system of Dukes to focus adjuvant therapy decisions. The purpose of this study was to determine whether K-ras mutational status of regional nodes in patients with Dukes B2 colorectal cancer could be used to stage their disease more accurately. METHODS: Using formalin-fixed, paraffin-embedded archival material, tumor samples were screened for K-ras mutations using a mutation-specific polymerase chain reaction method, followed by gel electrophoresis in a 96-well array. Patients with Dukes B2 tumors that have mutations in codon 12 or 13 of the K-ras gene were identified. RESULTS: Mutational analysis of the lymph nodes from these patients revealed an 80 percent (16/20) incidence of the same mutations in regional lymph nodes. None of the four patients with mutation-free nodes developed recurrence compared with 37.5 percent (6/16) with K-ras positive lymph nodes. CONCLUSIONS: The data suggest that patients with Dukes B2 colorectal cancers that have mutations in codon 12 or 13 of the K-ras gene are at high risk for the development of nodal metastases. Mutational analysis of the lymph nodes identifies high-risk patients who should be considered for adjuvant chemotherapy. Therefore, K-ras mutational analysis should be considered for molecular staging of colorectal cancer.

Introduction: the selenium conundrum.

Selenium was first suspected of being an essential dietary trace element in the 1950s. We now know that indeed it is an essential biological element that serves as an integral component of several enzymes, including those in the families of deiodinases and glutathione peroxidases as well as selenoproteins P and W. The multi-author review that follows this introduction concentrates on the important biological role of selenium in enzymes as well as some of the physiological aspects of selenium as either a potential anticarcinogenic agent or insulin mimetic. What should become clear from these contributed articles is the complex and dynamic role that selenium plays in many biological processes and that the investigations in these areas are at the edge of exciting new frontiers.

Selenium: an insulin-mimetic.

Insulin or agents that can mimic its action (insulin-mimetics) are necessary to promote the entry of glucose into tissues where the glucose can either be converted into energy or stored for later use. In recent years, selenium has been shown to mediate a number of insulin-like actions both in vivo and in vitro. These insulin-like actions include stimulating glucose uptake and regulating metabolic processes such as glycolysis, gluconeogenesis, fatty acid synthesis and the pentose phosphate pathway. The mechanism by which selenium is capable of mimicking insulin is not clear; however, reports indicate that selenium does activate key proteins involved in the insulin-signal cascade. Various proteins in the insulin-signal cascade have been shown to be necessary for different insulin-regulated events, and presumably data will be forthcoming soon that illustrate this similarly for selenium. This review compares the action of selenium to that of insulin and discusses the available evidence in support of selenium as an insulin-mimetic.

Inhibitory actions of synthesised polyamine spider toxins and their analogues on Ca2+-activated Cl- currents recorded from cultured DRG neurones from neonatal rats.

The whole cell variant of the patch clamp technique was used to investigate the actions of polyamine spider toxins and their analogues on high voltage-activated Ca2+ currents and Ca2+-activated Cl- currents (I(Cl(Ca))). The actions of synthesised FTX (putative natural toxin from the American funnel web spider), sFTX-3.3, Orn-FTX-3.3, Lys-FTX-3.3, and argiotoxin-636 on cultured dorsal root ganglion neurones from neonatal rats were investigated. Synthesised FTX (1 microM) inhibited I(Cl(Ca)) but did not inhibit high voltage-activated Ca2+ currents. In contrast, sFTX-3.3 (10 microM) inhibited both high voltage-activated Ca2+ currents and the associated I(Cl(Ca)) in near equal proportions. Argiotoxin-636 (1-10 microM) inhibited I(Cl(Ca)) evoked by Ca2+ entry through voltage-activated channels and by intracellular photorelease of Ca2+ from a caged precursor DM-nitrophen. This data indicates that synthesised FTX and argiotoxin-636 directly inhibit Ca2+-activated Cl- channels. In conclusion, the potency of polyamines as non-selective inhibitors of Ca2+ channels and Ca2+-activated Cl- channels is in part determined by the presence of a terminal arginine and this may involve an interaction between terminal guanidino groups and Ca2+ binding sites.

Insulin regulation of glucose-6-phosphate dehydrogenase gene expression is rapamycin-sensitive and requires phosphatidylinositol 3-kinase.

Glucose-6-phosphate dehydrogenase (G6PDH) controls the flow of carbon through the pentose phosphate pathway and also produces NADPH needed for maintenance of reduced glutathione and reductive biosynthesis. Hepatic expression of G6PDH is known to respond to several dietary and hormonal factors, but the mechanism behind regulation of this expression has not been characterized. We show that insulin similarly induces expression of endogenous hepatic G6PDH and a reporter construct containing 935 base pairs of the G6PDH promoter linked to luciferase in transient transfection assays. Using well tested and structurally distinct inhibitors of Ras farnesylation, lovastatin and B581, and a specific inhibitor of mitogen-activated protein kinase kinase activation, PD 98059, we show that the Ras/Raf/mitogen-activated protein kinase pathway is not utilized for the insulin-induced stimulation of G6PDH gene expression in primary rat hepatocytes. Similarly, using well characterized inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY 294002, we show that PI 3-kinase activity is necessary for the induction of G6PDH expression by insulin. Rapamycin, an inhibitor of FRAP protein, which is involved in the activation of pp70 S6 kinase, blocks the insulin induction of G6PDH, suggesting that S6 kinase is also necessary for the insulin induction of G6PDH expression.

Team building. Making collaborative practice work.

Collaborative practice offers great promise for maximizing the unique contributions and enhancing the satisfaction of everyone involved in health care, including the consumer. Developing collaborative relationships, however, requires much time and effort. Significant attitudinal, institutional, and behavioral barriers exist. Collaboration occurs between individuals, and each one must understand the concept of collaboration and be committed to investing the time and energy required to develop the relationship and overcome the barriers. The author describes critical attributes of collaboration and discusses how they can be developed and demonstrated.