Design of a compact off-axis four-mirror objective system for a thermal camera.

The optical design of a compact off-axis four-mirror objective system (OFOS) of a thermal camera for a syndromic surveillance system that captures bioclinical signals, like temperature, directly related to the physical symptoms of the COVID-19 disease through thermal images is presented. The OFOS design works on wavelengths of 7.5-14 µm, with an f-number of 4, and a field of view (FOV) of 24×4 deg.

Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss.

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.

Leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages.

Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1ß, IL-12p70 and IL-10 in human macrophages.

Population-based comparison of prognostic factors in invasive micropapillary and invasive ductal carcinoma of the breast.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a variant of breast carcinoma with a higher propensity for lymph node metastases compared with invasive ductal carcinoma (IDC). METHODS: Retrospective analysis of 636 IMPC and 297 735 IDC cases in the Surveillance, Epidemiology and End RESULTS database comparing disease-specific survival (DSS) and overall survival (OS) between IMPC and IDC. RESULTS: A higher percentage of IMPC cases (52.0%) had nodal metastases compared with IDC cases (34.6%). The 5-year DSS and OS for IMPC was 91.8% and 82.9%, respectively compared with 88.6% and 80.5% for IDC, respectively. For both IMPC and IDC, oestrogen-receptor positivity was associated with better survival, while having four or more positive lymph nodes or larger tumour size correlated with worse survival. Radiotherapy provided a survival benefit for both histological types. CONCLUSIONS: Despite IMPC's higher propensity for lymph node metastasis, IMPC has DSS and OS that compare favourably with IDC.

Graph-based symbolic technique and its application in the frequency response bound analysis of analog integrated circuits.

A new graph-based symbolic technique (GBST) for deriving exact analytical expressions like the transfer function H(s) of an analog integrated circuit (IC), is introduced herein. The derived H(s) of a given analog IC is used to compute the frequency response bounds (maximum and minimum) associated to the magnitude and phase of H(s), subject to some ranges of process variational parameters, and by performing nonlinear constrained optimization. Our simulations demonstrate the usefulness of the new GBST for deriving the exact symbolic expression for H(s), and the last section highlights the good agreement between the frequency response bounds computed by our variational analysis approach versus traditional Monte Carlo simulations. As a conclusion, performing variational analysis using our proposed GBST for computing the frequency response bounds of analog ICs, shows a gain in computing time of 100x for a differential circuit topology and 50x for a 3-stage amplifier, compared to traditional Monte Carlo simulations.

Predictors of overload in parents of children with neuromuscular diseases.

Introduction: Parents of children with neuromuscular diseases experience multiple difficulties in their daily lives that affect their physical and psychological health. The risk factors for these health issues have not been sufficiently investigated. Therefore, the aim of this study was to analyze the potential predictors of overload in these parents, including QoL, somatic symptomatology, life satisfaction, psychological adjustment and certain sociodemographic variables. Methods: A cross-sectional research study was conducted among parents who are caregivers for children with NMD in Spain. A convenience sample of 110 parents who were contacted by associations and hospitals was used. Variables were evaluated using the sociodemographic questionnaire, CarerQol-7D, PHQ-15, Barthel Index, Psychological Adaptation Scale, Zarit Overload Scale and Satisfaction with Life Scale. Results: One of the most relevant findings of the present study is the identification of 3 overload groups (mild to moderate, moderate to severe, and severe overload) based on life satisfaction and somatic symptom scores within the predictive model of the discriminate analysis. Wilk's lambda of the discriminant function was 0.568, χ2 (2, n = 55) = 8.815, p < 0.001. Discussion: This study presents a model that reveals the influence of unemployment, having a child with a severe level of dependency, the presence of somatic symptomatology and life satisfaction on caregiver overload. Likewise, the caregiver's self-esteem could be a protective factor against overload.

Cognitive Functioning in Adults with Phenylketonuria in a Cohort of Spanish Patients.

The early introduction of a low phenylalanine (Phe) diet has been demonstrated to be the most successful treatment in subjects with phenylketonuria (PKU), especially for preventing severe cognitive and neurological damages. However, it still concerns that even if treated in the first months of life with supplements and following a diet, they can show slight scores below people without PKU in neuropsychological assignments. We investigated 20 adults with classical PKU aged 19-48 years (mean age 29 years) and 20 heathy controls matched by age, gender, and years of education. Patients and controls were assessed with an extended neuropsychological battery, as well as psychological aspects and quality of life, also the last Phe level result was obtained. Results showed that the most affected cognitive domains are processing speed, executive functioning, memory, and also theory of mind, but very well-preserved verbal fluency, language, and visuospatial functioning. In quality of life, some significant results were seen specially in anxiety of Phe levels, anxiety of Phe levels during pregnancy, guilt if poor adherence to supplements, and if dietary protein restriction not followed. No significant results were obtained for the psychological variables. In conclusion, it has been shown that a combination of a low Phe diet, supplement intake, and keeping Phe levels in a low range seems appropriate to have the most normal and alike cognitive performance to persons without PKU.

Music therapy and Sanfilippo syndrome: an analysis of psychological and physiological variables of three case studies.

INTRODUCTION: Mucopolysaccharidosis type III (MPS III) or Sanfilippo syndrome is a neurodegenerative disease caused by the accumulation of mucopolysaccharides in the body. As the symptoms are wide ranging, it is a challenge to provide a diagnosis and psychological treatment for affected children. METHOD: The main objective of this study was to describe a form of music therapy treatment applied to three children diagnosed with MPS III. The psychological variables were evaluated by an ad hoc observation recording template, and the physiological variables were measured with a digital meter before and after each session. The perception of the parents was also considered through a semi-structured interview. RESULTS: An improvement in the psychological variables was shown in all cases. Changes in the physiological variables were also noted, although they varied according to each child. The parents report some benefit of music therapy and they share difficulty in assessing the extent of benefits of the music therapy. DISCUSSION: Findings indicate that music therapy can be a useful form of treatment with multiple benefits for children with conditions such as MPS III or similar conditions. However, further research is needed in this area and in the development of specific ways of evaluating music therapy.

Ketogenic diet and cognition in neurological diseases: a systematic review.

CONTEXT: In recent years, the ketogenic diet has gained special relevance as a possible therapeutic alternative to some neurological and chronic diseases. OBJECTIVE: The aim of this systematic review was to answer the following question: Does a ketogenic diet improve cognitive skills in patients with Alzheimer's disease, Parkinson's disease, refractory epilepsy, and type 1 glucose deficiency syndrome? To define the research question, the PICOS criteria were used, following the guidelines of the PRISMA method. DATA SOURCES: Medline/PubMed, Elsevier Science Direct, Dialnet, EBSCOhost, Mediagraphic, Sage Journals, ProQuest, and Wiley Online Library databases were used. DATA EXTRACTION: After applying inclusion and exclusion criteria in accordance with the PRISMA method, a total of 63 entries published between 2004 and 2019 were used. DATA ANALYSIS: The records extracted were analyzed from a qualitative approach, so no statistical analysis was carried out. CONCLUSION: Although scientific literature on the subject is scarce and there has tended to be a lack of scientific rigor, the studies reviewed confirmed the effectiveness of this diet in improving the cognitive symptomatology of the aforementioned diseases.

DNA repair signature is associated with anthracycline response in triple negative breast cancer patients.

We hypothesized that a subset of sporadic triple negative (TN) breast cancer patients whose tumors have defective DNA repair similar to BRCA1-associated tumors are more likely to exhibit up-regulation of DNA repair-related genes, anthracycline-sensitivity, and taxane-resistance. We derived a defective DNA repair gene expression signature of 334 genes by applying a previously published BRCA1-associated expression pattern to three datasets of sporadic TN breast cancers. We confirmed a subset of 69 of the most differentially expressed genes by quantitative RT-PCR, using a low density custom array (LDA). Next, we tested the association of this DNA repair microarray signature expression with pathologic response in neoadjuvant anthracycline trials of FEC (n = 50) and AC (n = 16), or taxane-based TET chemotherapy (n = 39). Finally, we collected paraffin-fixed, formalin-embedded biopsies from TN patients who had received neoadjuvant AC (n = 28), and tested the utility of the LDA to discriminate response. Correlation between RNA expression measured by the microarrays and 69-gene LDA was ascertained. This defective DNA repair microarray gene expression pattern was significantly associated with anthracycline response and taxane resistance, with the area under the ordinary receiver operating characteristic curve (AUC) of 0.61 (95% CI = 0.45-0.77), and 0.65 (95% CI = 0.46-0.85), respectively. From the FFPE samples, the 69-gene LDA could discriminate AC responders, with AUC of 0.79 (95% CI = 0.59-0.98). In conclusion, a promising defective DNA repair gene expression signature appears to differentiate TN breast cancers that are sensitive to anthracyclines and resistant to taxane-based chemotherapy, and should be tested in clinical trials with other DNA-damaging agents and PARP-1 inhibitors.

Experimental and theoretical analysis of the reorientational dynamics of fullerene C70 in various aromatic solvents.

A previous study of C70 in deuterated chlorobenzene generated evidence suggesting C70 was experiencing unique reorientational behavior at given temperatures. The present study explores the possibility that this behavior is present across other solvents. The 13C spin-lattice relaxation rates for four carbon resonances in C70 were analyzed in benzene-d6, chlorobenzene-d5, and o-dichlorobenzene-d4, and as a function of temperature, to probe the reorientational dynamics of this fullerene. Anisotropic behavior was observed at the lowest (283 K) and highest temperatures (323 K), isotropic diffusion was seen between 293 and 303 K, and quasi-isotropic at 313 K. When anisotropic motion was present, diffusion about the figure axis was seen to be higher than diffusion of the figure axis. Experimentally obtained diffusion coefficients generated reorientational correlation times that were in excellent agreement with experimental values. Theoretical predictions generated by a modified Gierer-Wirtz model provided acceptable predictions of the diffusion constants; with DX usually being more closely reproduced and DZ values generally being underestimated. Overall, the results indicate that the factors affecting rotational behavior are complex and that multiple solvent factors are necessary to characterize the overall motion of C70 in these solvents. Although a solvent's viscosity is normally sufficient to characterize the tumbling motion, the spinning motion is less sensitive to solvent viscosity but more responsive to solvent structure. The balance and collective influence of these factors ultimately determines the overall rotational behavior.

Patterns of venous insufficiency in patients with varicose veins.

The nature and distribution of venous disease surrounding the development of varicose veins and its treatment is controversial. Using duplex ultrasonography, we evaluated 54 lower extremities in 32 patients with varicose veins who were symptomatic and had obvious varicose veins by clinical examination. Twenty-eight percent had greater saphenous trunk incompetence, 2% had lesser saphenous trunk incompetence, and 96% had branch disease. Deep valvular incompetence was seen in 41%, saphenofemoral junction incompetence in 46%, and incompetence of one or more perforators in 46% of the extremities. Thirty-three percent demonstrated no evidence of associated saphenofemoral junction, deep vein, or perforating vein incompetence, while 20% had concurrent saphenofemoral junction, deep vein, and perforating vein incompetence. These data support the heterogeneity of venous disease seen in patients with varicose veins and suggest that surgical therapy be directed to a patient's specific pattern of incompetence rather than routine saphenofemoral junction ligation or stripping of the greater saphenous trunk.

Liver viability after ischemia-reperfusion.

Lack of a reproducible model to quantitatively assess hepatocellular injury following ischemia has made it difficult to assess new strategies for minimizing hepatic injury. We studied the progression of hepatocellular injury after ischemia and ischemia with reperfusion in rats. Irreversible injury was quantitated using a triphenyltetrazolium chloride assay that was shown to correlate with ultrastructural changes. Adenosine triphosphate decreased to 36% of basal values after 30 minutes, but returned to normal with reperfusion with no decrease in viability. In contrast, viability fell by 30% after 60 minutes of ischemia, and by 64% when 60 minutes of ischemia was followed by reperfusion. We conclude that reperfusion of ischemic liver increases the degree of irreversible damage. The model employed here seems to be useful for studying ischemic and reperfusion injury in the liver.

Antimicrobial susceptibility of Listeria monocytogenes isolated from meningoencephalitis in sheep.

The antimicrobial susceptibility to different antimicrobial agents of 41 Listeria monocytogenes strains isolated from sheep with meningoencephalitis and from feedstuff was tested by both microdilution and disk diffusion methods. Both sets of isolates of L. monocytogenes were susceptible to penicillin G, amoxicillin, cephalothin, erythromycin, vancomycin, rifampicin, gentamicin, kanamycin, trimethoprim, sulfisoxazole, chloramphenicol and ciprofloxacin, but resistant to tetracycline and doxycycline (7.3 and 4.9%, respectively). Tetracycline was the most frequent resistance trait in L. monocytogenes strains of animal origin. Four strains (9.8%) also exhibited reduced susceptibility (MIC 4 mg/l) to doxycycline suggesting the need of surveillance studies to monitor the antimicrobial resistance of Listeria strains of animal origin.

Evaluation of the perforating veins of the lower extremity using high resolution duplex imaging.

The purpose of this study was to evaluate duplex imaging as a means of assessing perforating veins in patients with longstanding venous stasis ulceration. Thirty patients with nonhealing venous stasis ulcers and twenty normal volunteers serving as controls were evaluated with a standard 8-MHz imaging probe and integrated pulsed Doppler. The internal diameter of perforating veins was measured and perforators were grouped into one of four categories based on functional criteria: competent perforator with venous flow (C); incompetent perforator with venous flow (IC); competent perforator with arteriovenous flow (C-AVC); incompetent perforator with arteriovenous flow (IC-AVC). Sixteen of the patients with ulcers were subsequently studied by ascending venography and in 11 patients, intraoperative identification of perforating veins was made during the Rob procedure. In this subset of patients the vessel was categorized as competent or incompetent regardless of flow signal. There were significant differences in mean perforator diameter between ulcer patients and normal volunteers. Duplex imaging identified 93 perforators and venography a total of 70. In all 16 extremities, duplex imaging made the diagnosis of significant perforating vein incompetence, verified by venography. Intraoperative findings demonstrated an excellent correlation with duplex imaging. We believe duplex imaging to be a promising new modality for evaluation of the perforating veins of the lower extremity.

Nuclear imaging in Coccidioidal osteomyelitis.

Six cases of osteomyelitis due to Coccidioides immitis are presented. The cases reported demonstrate the importance of performing both bone and gallium imaging to avoid missing the osseous coccidioidal lesions.

One-dose technetium-99m pertechnetate imaging in acute testicular torsion followed by manual detorsion.

The role of technetium-99m pertechnetate imaging in acute testicular torsion is well appreciated. Manual testicular detorsion under local anesthesia may be performed in the nuclear medicine clinic by the urology service immediately following initial diagnostic scintigraphy. Following manual testicular detorsion, continued images of the testes are obtained up to 30 minutes without having to reinject the patient with technetium-99m pertechnetate. Reperfusion of the affected testicle will be dramatically noted if the manual detorsion is successful. Four cases are presented to illustrate this.

Serendipitous finding of transitional cell carcinoma of the kidney on bone and gallium imaging.

A 50-year-old woman presented with low back pain. Bone scintigraphy showed a focus of increased activity in the upper pole of the left kidney. Subsequent Ga-67 citrate scintigraphy demonstrated this same abnormal focus as a region of increased activity. Ultrasonography showed a renal mass in the upper pole of the left kidney. At surgery a transitional cell carcinoma of the upper pole of the left kidney was found.

Adenomyosis as seen on blood flow and blood pool imaging during bone scintigraphy.

A 42-year-old woman presented with intermittent low back and left lower extremity pain. The blood flow and blood pool images of bone scintigraphy showed a large focus of increased activity in the right lower abdomen. Computed tomography showed an enlarged uterus displaced to the right side of the pelvis. At surgery, the uterus was found to be involved with adenomyosis. Three-phase bone scintigraphy consisting of blood flow and blood pool images over the anterior pelvis may be a valuable diagnostic aid in the evaluation of lower back or pelvic pain of a woman.