Investigation of saliva, tongue swabs and buccal swabs as alternative specimen types to nasopharyngeal swabs for SARS-CoV-2 testing.

Throughout the ongoing SARS-CoV-2 pandemic, the recommended sample type for initial diagnostic testing for SARS-CoV-2 infection has been a nasopharyngeal swab. Shortages in swabs and difficulties in obtaining nasopharyngeal swabs in certain patient groups has prompted research into alternative specimen types for the diagnosis of COVID-19. The aim of this study was to assess how 'simply collected' saliva along with tongue swabs and buccal swabs preformed as an alternative specimen type for SARS-CoV-2 detection. It was observed that saliva samples allowed for the detection of 85.3% of positive patients, tongue swabs allowed for the detection of 67.6% of positive patients and buccal swabs allowed for detection of 20.8% of positive patients, when compared to nasopharyngeal swabs. From this data, it could be concluded that using simple saliva collection can provide a less invasive and reliable alternative method for the detection of SARS-CoV2 particularly in those patients where invasive sampling is difficult and where regular repeat testing is required.

6450 nm wavelength tissue ablation using a nanosecond laser based on difference frequency mixing and stimulated Raman scattering.

A four-stage laser system was developed, emitting at a wavelength of 6450 nm with a 3-5 ns pulse duration, < or = 2 mJ pulse energy, and 1/2 Hz pulse repetition rate. The laser system successfully ablated rat brain tissue, where both the collateral damage and the ablation rate compare favorably with that previously observed with a Mark-III Free-Electron Laser.

Increased level of chromosomal damage after irradiation of lymphocytes from BRCA1 mutation carriers.

Deleterious mutations in the BRCA1 gene predispose women to an increased risk of breast and ovarian cancer. Many functional studies have suggested that BRCA1 has a role in DNA damage repair and failure in the DNA damage response pathway often leads to the accumulation of chromosomal aberrations. Here, we have compared normal lymphocytes with those heterozygous for a BRCA1 mutation. Short-term cultures were irradiated (8Gy) using a high dose rate and subsequently metaphases were analysed by 24-colour chromosome painting (M-FISH). We scored the chromosomal rearrangements in the metaphases from five BRCA1 mutation carriers and from five noncarrier control samples 6 days after irradiation. A significantly higher level of chromosomal damage was detected in the lymphocytes heterozygous for BRCA1 mutations compared with normal controls; the average number of aberrations per mitosis was 3.48 compared with 1.62 in controls (P=0.0001). This provides new evidence that heterozygous mutation carriers have a different response to DNA damage compared with noncarriers and that BRCA1 has a role in DNA damage surveillance. Our finding has implications for treatment and screening of BRCA1 mutation carriers using modalities that involve irradiation.

Long-term survival of intratesticular porcine islets in nonimmunosuppressed beagles.

BACKGROUND: The testis is an immunoprivileged organ, and at 37 degrees C, the intratesticular microenvironment supports the survival of allogeneic islets. The objective of this study was to determine whether the immunoprotection afforded by the intratesticular environment is potent enough to prevent the rejection of xenogeneic porcine islets in a large-animal model. METHODS: A bilateral cryptorchid condition was surgically created in sexually mature beagle dogs. Porcine islets were prepared from neonatal pigs by collagenase digestion and 9 days of culture, after which they were injected into each of the cryptorchid testes. Control dogs received liver subcapsular space transplants of porcine islets and autologous islets. After 100 days, the testes and relevant portions of liver were studied immunohistochemically for the presence of islet tissue. RESULTS: The testicular interstitial space of all dogs contained abundant islet tissue. No evidence of lymphocytic infiltration or inflammation was observed. In contrast, porcine islets transplanted to the liver subcapsular space do not survive, although autologous islets engraft well in that position. This occurs even though the recipient's serum contains preformed cytotoxic antibodies to porcine islets that persist after transplantation. CONCLUSIONS: These results demonstrate that the microenvironment existing within the surgically repositioned intra-abdominal testis supports the survival of xenogeneic tissue. The survival of xenogeneic tissue in the absence of immunosuppression in this large-animal model raises the possibility that xenogeneic porcine islet tissue will also survive in humans if transplanted into a similar environment.

Toward a biologically based dose-response model for developmental toxicity of 5-fluorouracil in the rat: acquisition of experimental data.

Biologically based dose-response (BBDR) models represent an emerging approach to improving the current practice of human health-risk assessment. The concept of BBDR modeling is to incorporate mechanistic information about a chemical that is relevant to the expression of its toxicity into descriptive mathematical terms, thereby providing a quantitative model that will enhance the ability for low-dose and cross-species extrapolation. Construction of a BBDR model for developmental toxicity is particularly complicated by the multitude of possible mechanisms. Thus, a few model assumptions were made. The current study illustrates the processes involved in selecting the relevant information for BBDR modeling, using an established developmental toxicant, 5-fluorouracil (5-FU), as a prototypic example. The primary BBDR model for 5-FU is based on inhibition of thymidylate synthetase (TS) and resultant changes in nucleotide pools, DNA synthesis, cell-cycle progression, and somatic growth. A single subcutaneous injection of 5-FU at doses ranging from 1 to 40 mg/kg was given to pregnant Sprague-Dawley rats at gestational day 14; controls received saline. 5-FU was absorbed rapidly into the maternal circulation, and AUC estimates were linear with administered doses. We found metabolites of 5-FU directly incorporated into embryonic nucleic acids, although the levels of incorporation were low and lacked correlation with administered doses. On the other hand, 5-FU produced dose-dependent inhibition of thymidylate synthetase in the whole embryo, and recovery from enzyme inhibition was also related to the administered dose. As a consequence of TS inhibition, embryonic dTTP and dGTP were markedly reduced, while dCTP was profoundly elevated, perhaps due to feedback regulation of intracellular nucleotide pools. The total contents of embryonic macromolecules (DNA and protein) were also reduced, most notably at the high doses. Correspondingly, dose-related reductions of fetal weight were seen as early as GD 15, and these deficits persisted for the remainder of gestation. These detailed dose-response parameters involved in the expression of 5-FU developmental toxicity were incorporated into mathematical terms for BBDR modeling. Such quantitative models should be instrumental to the improvement of high-to-low dose and cross-species extrapolation in health-risk assessment.

Toward a biologically based dose-response model for developmental toxicity of 5-fluorouracil in the rat: a mathematical construct.

Biologically based dose-response (BBDR) models comprise one way to incorporate mechanistic information into a dose-response assessment to be used for risk assessments. The chemotherapeutic drug 5-fluorouracil (5-FU) has been used as a prototypic compound for the construction of a BBDR model for developmental toxicity. Previous work has provided data and a general mechanistic framework for the developmental toxicity of 5-FU when it was administered to pregnant rats subcutaneously on gestation day 14. In this paper, a mathematical model relating maternally administered treatment with 5-FU to embryonal thymidylate synthetase inhibition and thymidylate synthetase inhibition to various measures of deoxyribonucleotide triphosphate (dNTP) pool perturbation is developed, and parameters are estimated using the data collected. The strategy used was to develop semi-empirical submodels for each of the intervening steps, and to estimate model parameters from previously described data. The models developed predict that there is no practical threshold for dNTP pool perturbation; that is, even minimal doses of 5-FU should result in some perturbation of dNTP pools. In particular, the relationship between dNTP pool perturbation and fetal weight deficit suggests that if there is a biological threshold for the effect of 5-FU on fetal weight, the responsible repair or compensation mechanism must be downstream of dNTP pool perturbation, and saturable at 5-FU doses lower than 10 mg/kg (the lowest dose examined for developmental effects in these studies).

What recovery means to us: consumers' perspectives.

In this article two consumer leaders use their own experiences to explain the meaning and significance of recovery. They emphasize the importance of hope, personal responsibility, education, advocacy, and peer support. They also address controversial issues, such as the nature of the therapeutic relationship, the place of medications in symptom control, and the need for attitudinal changes in mental health professionals.

Predicting conversion to Alzheimer disease using standardized clinical information.

OBJECTIVE: To identify aspects of a standardized clinical assessment that can predict which individuals within the category of "questionable" Alzheimer disease (AD) have a high likelihood of converting to AD over time. DESIGN: Detailed semistructured interviews were performed at baseline and annually for 3 years. SETTING: University-based gerontology research program. PATIENTS: The patient population consisted of 165 individuals 65 years and older: 42 of the participants had a Clinical Dementia Rating (CDR) of normal cognition (CDR rating, 0.0) and 123 had a rating of questionable AD (CDR rating, 0.5). After 3 years of follow-up, 23 of the 123 subjects with questionable AD were diagnosed with probable AD. MAIN OUTCOME MEASURES: The interview was used to generate a summary measure based on the sum of 6 CDR categories, known as the Total Box Score. The responses to 32 selected questions from the interview also were examined. RESULTS: Likelihood of progression to AD during the follow-up period was strongly related to the Total Box Score. For example, more than 50% of individuals with a Total Box Score of 2.0 or higher at baseline developed AD during the follow-up interval, whereas about 10% of individuals with a Total Box Score of 1.0 or lower developed AD during this same period. Selected questions from the standardized clinical interview also were highly predictive of subsequent conversion to AD among the study population. Eight selected questions from the clinical interview at baseline, combined with the CDR Total Box Score, identified 88.6% of such individuals accurately (questionable group, 82/91; converter group, 19/23). CONCLUSIONS: A standardized clinical assessment can be used to identify the subgroup of individuals within the category of questionable AD who have a high likelihood of converting to AD over time. Subjects who met the criteria for questionable AD had a variety of trajectories during a 3-year follow-up, suggesting that diverse factors may influence the functional changes observed in this population.

Molecular linkage underlying microtubule orientation toward cortical sites in yeast.

Selective microtubule orientation toward spatially defined cortical sites is critical to polarized cellular processes as diverse as axon outgrowth and T cell cytotoxicity. In yeast, oriented cytoplasmic microtubules align the mitotic spindle between mother and bud. The cortical marker protein Kar9 localizes to the bud tip and is required for the orientation of microtubules toward this region. Here, we show that Kar9 directs microtubule orientation by acting through Bim1, a conserved microtubule-binding protein. Bim1 homolog EB1 was originally identified through its interaction with adenomatous polyposis coli (APC) tumor suppressor, raising the possibility that an APC-EB1 linkage orients microtubules in higher cells.

Recovery-oriented psychopharmacology: redefining the goals of antipsychotic treatment.

The traditional goals of psychopharmacology stem from the medical model. Rehabilitation interventions attempt to improve aspects of functioning in patients with chronic illnesses that are not responsive to biological intervention. Recovery is a concept emanating from the consumer self-help movement. It describes a move away from the patient role defined by a diagnostic label toward community membership defined by relationships and responsibilities in the community. Comprehensive care for people with psychotic disorders can include attention to each realm. This article provides an overview of the 3 models of care and describes a role for the psychopharmacologist in each as well as his or her unique potential to incorporate all 3. We outline potential synergistic benefits of integrating recovery-, rehabilitation-, and medical-model thinking into the practice of psychopharmacology and explore implications for the goals and outcomes of treatment for people with psychotic disorders.

Pigmented schwannoma of the ventral spinal cord.

Pigmented schwannomas of the spinal canal are rare entities. We present a case of such in an unusual, ventral intradural, extramedullary location in a 27-year-old man. Imaging and histopathologic findings, including electron microscopy, showed an intradural, extramedullary pigmented schwannoma, densely adherent to the leptomeninges of the anterior median septum. This lesion is demonstrative of the neuroectodermal origin of these lesions and represents a rare location of these tumors.

Stereotactic ventriculoperitoneal shunt for idiopathic intracranial hypertension: technical note.

OBJECTIVE: Lumboperitoneal shunting is the bastion of neurosurgical management for idiopathic intracranial hypertension (IIH). However, recent studies document a high failure rate for this procedure. The present study was designed to explore the feasibility of placing ventriculoperitoneal shunts under stereotactic control into patients with IIH as an alternative to lumboperitoneal shunting. METHODS: Seven patients with IIH for whom medical management had failed underwent stereotactic implantation of ventriculoperitoneal shunts. RESULTS: Shunt placement was successful and uncomplicated in each case. Five of seven patients experienced complete resolution of papilledema. The remaining two patients showed resolving papilledema. Six of seven patients experienced resolution of headache. The remaining patient continued to have headaches despite a radionuclide study demonstrating normal shunt function. CONCLUSION: Our results suggest that stereotactic ventriculoperitoneal shunting may be a reasonable alternative to lumboperitoneal shunting in those patients with IIH who require surgical intervention.

Silicone breakdown and capsular synovial metaplasia in textured-wall saline breast prostheses.

Saline-filled prostheses are currently the only type of prostheses available for cosmetic use in the United States because of concerns raised about the possibility of systemic toxicity of silicone-filled artificial mammary implants. Although the approved implants are saline-filled, their potential to release silicone particles from the shells has not been systematically evaluated. We performed microscopic examination of the pericapsular tissue of 54 patients with textured-surface implants and compared these with 51 patients with smooth-walled implants over a 2-year period. The capsules that had formed around virtually all textured-surface implants had silicone fragments present either in extracellular spaces, in vacuolated histiocytes, or in the form of foreign-body granulomas in surrounding fibroadipose tissue but not in capsules associated with smooth-walled implants. In 87 percent of samples of pericapsular tissue from textured saline implants, the contact surface displayed exuberant reactive synovial metaplasia, a histologic pattern not previously described with these devices. Our findings suggest that smooth-walled prostheses are associated with less silicone fragmentation than textured devices in the peri-implant tissue capsules that tend to form around artificial surfaces used for this purpose.

Tissue ablation by a free-electron laser tuned to the amide II band.

Efforts to ablate soft tissue with conventional lasers have been limited by collateral damage and by concern over potential photochemical effects. Motivated by the thermal-confinement model, past infrared investigations targeted the OH-stretch mode of water with fast pulses from lasers emitting near 3,000 nm (refs 1, 7-9). What does a free-electron laser offer for the investigation of tissue ablation? Operating at non-photochemical single-photon energies, these infrared sources can produce trains of picosecond pulses tunable to the vibrational modes of proteins, lipids and/or water. We report here that targeting free-electron laser radiation to the amide II band of proteins leads to tissue ablation characterized by minimal collateral damage while maintaining a substantial ablation rate. To account for these observations we propose a novel ablation mechanism based on compromising tissue through resonant denaturation of structural proteins.

Breast size as a risk factor for sternal wound complications following cardiac surgery.

OBJECTIVE: To determine if macromastia is associated with risk for deep sternal wound infection following cardiac surgery via median sternotomy incision. DESIGN: Case-control study. SETTING: Private urban teaching hospital. PARTICIPANTS: Women who developed deep sternal wound infection after undergoing cardiac surgery via median sternotomy incision and a random sample of women who did not develop infection following the same surgery. OUTCOME MEASURES: Odds ratios (ORs) were used to compare the development of deep sternal wound infection in women who wore large bra cups (size D or DD) with women who wore small bra cups (size A or B) and to compare women who wore medium bra cups (size C) with those who wore small bra cups. RESULTS: For women who wore large bra cups, the OR for deep sternal wound infection was 38.5 (95% confidence interval [CI], 5.6 to 265.8) compared with women who wore small bra cups. For women who wore medium bra cups, the OR for deep sternal wound infection was 12.3 (95% CI, 2.2 to 68.7). The multivariate adjusted ORs, controlling for body mass index, internal mammary artery grafting, diabetes, and age, were 42.1 (95% CI, 3.7 to 477.3) for women who wore large bra cups compared with women who wore small bra cups and 14.9 (95% CI, 1.7 to 129.7) for women who wore medium bra cups compared with women who wore small bra cups. CONCLUSIONS: Large and medium bra cups sizes are associated with an increased risk for deep sternal wound infection after undergoing cardiac surgery via median sternotomy incision.

Systemic inflammatory disorder related to fibrous breast capsules after silicone implant removal.

Silicone breast implants have been associated with connective-tissue inflammatory syndromes such as systemic sclerosis, and as with other artificial breast prostheses, fibrous capsules tend to form around the implants. The capsular tissue is generally considered inert and typically is left in situ when the prostheses are explanted. We report a patient who formed symptomatic bilateral submammary cysts associated with pain, swelling, arthralgia, fever, axillary lymphadenopathy, accelerated erythrocyte sedimentation rate, and antinuclear antibody following removal of intact silicone breast implants without capsulectomy. Clinical improvement followed removal of the capsules, which histologically displayed fragments of silicone, fibrous tissue, and inflammatory cells. Our experience suggests that when silicone breast implants are thought to be the cause of a clinical inflammatory syndrome characterized by mammary pain, swelling, arthralgia, or serologic abnormalities, consideration should be given to removing the capsules entirely so that the chance of a perpetuating reaction will be reduced.