[Catatonia de novo, report on a case: immediate vital prognosis and psychiatric prognosis in longer term].
We report on the case of a 20 year old woman with no previous psychiatric history, who displayed a first episode of catatonia with acute onset. Symptoms started plainly with sudden general impairment, intense asthenia, headache, abdominal pain and confusion. After 48 hours, the patient was first admitted to an emergency unit and transferred to an internal medicine ward afterwards. She kept confused. Her behaviour was bizarre with permanent swinging of pelvis, mannerism, answers off the point and increasingly poor. The general clinical examination was normal, except for the presence of a regular tachycardia (120 bpm). The paraclinical investigations also showed normal: biology, EEG, CT Scan, lumbar puncture. Confusion persisted. The patient remained stuporous, with fixed gazing and listening-like attitudes. She managed to eat and move with the help of nurses but remained bedridden. The neurological examination showed hypokinaesia, extended hypotonia, sweating, urinary incontinence, bilateral sharp reflexes with no Babinski's sign and an inexhaustible nasoorbicular reflex. The patient was mute and contrary, actively closed her eyes, but responded occasionally to simple instructions. For short moments, she suddenly engaged in inappropriate behaviors (wandering around) while connecting back to her environment answering the telephone and talking to her parents. The patient's temperature rose twice in the first days but with no specific etiology found. During the first 8 days of hospitalization, an antipsychotic treatment was administered: haloperidol 10 mg per os daily and cyamemazine 37.5 mg i.m. daily. Despite these medications, the patient worsened and was transferred to our psychiatric unit in order to manage this catatonic picture with rapid onset for which no organic etiology was found. On admission, the patient was stuporous, immobile, unresponsive to any instruction, with catalepsy, maintenance of postures, severe negativism and refusal to eat. A first treatment by benzodiazepine (clorazepate 20 mg i.v.) did not lead to any improvement. The organic investigations were completed with cerebral MRI and the ruling out of a Wilson's disease. Convulsive therapy was then decided. It proved dramatically effective from the first attempt; 4 shocks were carried out before the patient's relatives ask for her discharge from hospital. The patient revealed she had experienced low delirium during her catatonic state. The clinical picture that followed showed retardation with anxiety. She was scared with fear both for the other patients and the nursing team. She kept distant and expressed few affects. The treatment at the time of discharge was olanzapine 10 mg per os. She was discharged with a diagnosis of catatonia but with no specific psychiatric etiological diagnosis associated. She discontinued her follow-up a few weeks later. After one year, we had no information about her. Catatonia has now become rare but remains a problem for clinicians. We reviewed data concerning short term vital prognosis and psychiatric long term prognosis in catatonia. Lethal catatonia is associated with acute onset, both marked psychomotor and neurovegetative symptoms. In the light of literature, there is no proband clinical criterion during the episode that is of relevant diagnostic value to ascertain the psychiatric etiology.


Phase-Locking Requires Efficient Ca2+ Extrusion at the Auditory Hair Cell Ribbon Synapse.
Proper perception of sounds in the environment requires auditory signals to be encoded with extraordinary temporal precision up to tens of microseconds, but how it originates from the hearing organs in the periphery is poorly understood. In particular, sound-evoked spikes in auditory afferent fibers in vivo are phase-locked to sound frequencies up to 5 kHz, but it is not clear how hair cells can handle intracellular Ca2+ changes with such high speed and efficiency. In this study, we combined patch-clamp recording and two-photon Ca2+ imaging to examine Ca2+ dynamics in hair cell ribbon synapses in the bullfrog amphibian papilla of both sexes. We found that Ca2+ clearance from single synaptic ribbons followed a double exponential function, and the weight of the fast component, but not the two time constants, was significantly reduced for prolonged stimulation, and during inhibition of the plasma membrane Ca2+ ATPase (PMCA), the mitochondrial Ca2+ uptake (MCU), or the sarcolemma/endoplasmic reticulum Ca2+ ATPase (SERCA), but not the Na+/Ca2+ exchanger (NCX). Furthermore, we found that both the basal Ca2+ level and the Ca2+ rise during sinusoidal stimulation were significantly increased by inhibition of PMCA, MCU, or SERCA. Consistently, phase-locking of synaptic vesicle releases from hair cells was also significantly reduced by blocking PMCA, MCU, or SERCA, but not NCX. We conclude that, in addition to fast diffusion mediated by mobile Ca2+ buffer, multiple Ca2+ extrusion pumps are required for phase-locking at the auditory hair cell ribbon synapse.SIGNIFICANCE STATEMENT Hair cell synapses can transmit sound-driven signals precisely in the kHz range. However, previous studies of Ca2+ handling in auditory hair cells have often been conducted in immature hair cells, with elevated extracellular Ca2+ concentration, or through steady-state stimulation that may not be physiologically relevant. Here we examine Ca2+ clearance from hair cell synaptic ribbons in a fully mature preparation at physiological concentration of external Ca2+ and at physiological temperature. By stimulating hair cells with sinusoidal voltage commands that mimic pure sound tones, we recapitulated the phase-locking of hair cell exocytosis with an in vitro approach. This allowed us to reveal the Ca2+ extrusion mechanisms that are required for phase-locking at auditory hair cell ribbon synapses.


Testing differential use of payoff-biased social learning strategies in children and chimpanzees.
Various non-human animal species have been shown to exhibit behavioural traditions. Importantly, this research has been guided by what we know of human culture, and the question of whether animal cultures may be homologous or analogous to our own culture. In this paper, we assess whether models of human cultural transmission are relevant to understanding biological fundamentals by investigating whether accounts of human payoff-biased social learning are relevant to chimpanzees (Pan troglodytes). We submitted 4- and 5-year-old children (N = 90) and captive chimpanzees (N = 69) to a token-reward exchange task. The results revealed different forms of payoff-biased learning across species and contexts. Specifically, following personal and social exposure to different tokens, children's exchange behaviour was consistent with proportional imitation, where choice is affected by both prior personally acquired and socially demonstrated token-reward information. However, when the socially derived information regarding token value was novel, children's behaviour was consistent with proportional observation; paying attention to socially derived information and ignoring their prior personal experience. By contrast, chimpanzees' token choice was governed by their own prior experience only, with no effect of social demonstration on token choice, conforming to proportional reservation. We also find evidence for individual- and group-level differences in behaviour in both species. Despite the difference in payoff strategies used, both chimpanzees and children adopted beneficial traits when available. However, the strategies of the children are expected to be the most beneficial in promoting flexible behaviour by enabling existing behaviours to be updated or replaced with new and often superior ones.


The wide-ranging clinical implications of the short telomere syndromes.
There is an increasing number of inherited disorders in which excessive telomere shortening underlies the molecular defect, with dyskeratosis congenita (DC) being the archetypal short telomere syndrome. DC is classically described as a mucocutaneous triad of oral leukoplakia, nail dystrophy and abnormal skin pigmentation. However, excessive telomere shortening can affect almost any organ system, so the clinical manifestations are protean, including developmental delay, cerebellar hypoplasia, exudative retinopathy, aplastic anaemia, acute myeloid leukaemia, idiopathic pulmonary fibrosis, idiopathic hepatic cirrhosis, head and neck cancer and dental abnormalities, and may be multi-systemic. Undiagnosed patients may be seen by essentially any medical subspecialist. Correct diagnosis is important to ensure appropriate management, and for initiating investigations to identify affected family members. Treatment is often supportive, with transplantation offering cure for pulmonary fibrosis or bone marrow failure. Higher rates of mortality and morbidity with transplantation often require regimen alterations, underscoring the need for correct diagnosis. Short telomeres result from mutations in genes essential for telomere maintenance (e.g. genes encoding subunits of the telomerase enzyme complex). Disease severity reflects not only the severity of the defect, but also the inheritance of short telomeres, giving rise to incomplete penetrance and genetic anticipation. Attendees of the inaugural Australian Short Telomere Syndrome Conference were updated on the current scientific and clinical understanding of these disorders, and discussed the best approach for management of these patients in the Australian context. This review will include recommendations from the conference and aims to increase awareness of short telomere disorders.


Looking Under the Hood of the Cadillac Tax.
One effect of the Affordable Care Act's "Cadillac tax" (now delayed until 2020) is to undo part of the existing federal tax preference for employer-sponsored insurance. The specific features of this tax on high-cost health plans--notably, the inclusion of tax-favored savings vehicles such as health savings accounts (HSAs) in the formula for determining who is subject to the tax--are designed primarily to maximize revenue and minimize coverage disruptions, not to reduce health spending. Thus, at least initially, these savings accounts, rather than enrollee cost-sharing or other plan features, are likely to be affected most by the tax as employers act to limit their HSA contributions. Because high earners are the ones benefiting most from tax-preferred accounts, the high-cost plan tax will probably be more progressive than prior analyses have suggested, while having only a modest impact on total health spending.


Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer.
Triple-negative breast cancer (TNBC) accounts for ∼20% of cases and contributes to basal and claudin-low molecular subclasses of the disease. TNBCs have poor prognosis, display frequent mutations in tumor suppressor gene p53 (TP53), and lack targeted therapies. The MET receptor tyrosine kinase is elevated in TNBC and transgenic Met models (Met(mt)) develop basal-like tumors. To investigate collaborating events in the genesis of TNBC, we generated Met(mt) mice with conditional loss of murine p53 (Trp53) in mammary epithelia. Somatic Trp53 loss, in combination with Met(mt), significantly increased tumor penetrance over Met(mt) or Trp53 loss alone. Unlike Met(mt) tumors, which are histologically diverse and enriched in a basal-like molecular signature, the majority of Met(mt) tumors with Trp53 loss displayed a spindloid pathology with a distinct molecular signature that resembles the human claudin-low subtype of TNBC, including diminished claudins, an epithelial-to-mesenchymal transition signature, and decreased expression of the microRNA-200 family. Moreover, although mammary specific loss of Trp53 promotes tumors with diverse pathologies, those with spindloid pathology and claudin-low signature display genomic Met amplification. In both models, MET activity is required for maintenance of the claudin-low morphological phenotype, in which MET inhibitors restore cell-cell junctions, rescue claudin 1 expression, and abrogate growth and dissemination of cells in vivo. Among human breast cancers, elevated levels of MET and stabilized TP53, indicative of mutation, correlate with highly proliferative TNBCs of poor outcome. This work shows synergy between MET and TP53 loss for claudin-low breast cancer, identifies a restricted claudin-low gene signature, and provides a rationale for anti-MET therapies in TNBC.


Adequate return to sports and sports activities after treatment of Lisfranc injury: a meta-analysis.
Although a large number of Lisfranc injuries occur during sports, data on sports outcomes, such as return to sport (RTS) rates and times as well as level of sports activities after treatment of this injury remain limited. The aim is to assess the RTS rates, times and the sports activity levels after different treatments of Lisfranc injuries. The electronic databases PubMed (MEDLINE), EMBASE, CDSR, DARE and CENTRAL were searched to identify relevant articles from January 1985 to July 2020. The mean RTS rates (to any level and preinjury level of sports) and times were extracted per study, and pooled wherever methodologically possible. Methodological quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies criteria (MINORS). Fifteen studies were included in this review. Methodological quality of the studies was poor. The treatments reported in the studies were conservative treatment, surgical fixation and primary partial arthrodesis. For conservative treatment, the RTS rate regardless of sports level was 93% (95% CI 81% to 98%; n=42) and for return to preinjury level of sports was 88% (95% CI 75% to 95%; n=42). The fixation group showed a RTS percentage of 94% (95% CI 91% to 97%; n=270) to each level of sports and for return to the level before injury was 86% (95% CI 80% to 90%; n=188). In the primary partial arthrodesis group, the return to any level of sports was 94% (95% CI 85% to 98%; n=65) and for return to preinjury level was 74% (95% CI 62% to 83%; n=65). Mean time to RTS ranged from 7 to 33 weeks across all treatment groups. No data pooling was possible for this outcome measure. From the different studies, a total of 43 different sports and 440 physical activities were reported before treatment. After treatment, patients participated in 37 different sports (88%) and 391 different physical activities (89%). The different treatment options for Lisfranc injuries allow for good sport-specific outcomes with 93% to 94% of athletes returning to any level of sports, and 74% to 88% of athletes returning to their preinjury level of sport. These sport-specific outcomes can be used to inform patients about their expected sport-specific outcomes after different treatments of Lisfranc injuries. Systematic review and meta-analysis.


Routine Clinical-Pathologic Correlation of Pigmented Skin Tumors Can Influence Patient Management.
Several studies have demonstrated the benefit of integrating clinical with pathologic information, to obtain a confident diagnosis for melanocytic tumors. However, all those studies were conducted retrospectively and no data are currently available about the role of a clinical-pathologic correlation approach on a daily basis in clinical practice. In our study, we evaluated the impact of a routine clinical-pathologic correlation approach for difficult skin tumors seen over 3 years in a tertiary referral center. Interestingly, a re-appraisal was requested for 158 out of 2015 (7.7%) excised lesions because clinical-pathologic correlation was missing. Of note, in 0.6% of them (13 out of 2045) the first histologic diagnosis was revised in the light of clinical information that assisted the Pathologist to re-evaluate the histopathologic findings that might be bland or inconspicuous per se. In conclusion, our study demonstrated that an integrated approach involving clinicians and pathologists allows improving management of selected patients by shifting from a simply disease-focused management (melanoma versus nevus) to a patient-centered approach.


Interleukin 8, a Biomarker to Differentiate Guillain-Barré Syndrome From CIDP.
To determine whether CSF interleukin 8 (IL-8) concentration can help to distinguish Guillain-Barré syndrome (GBS) from chronic inflammatory demyelinating polyneuropathy (CIDP) at the initial stage of the disease. We performed retrospective immunoassay of IL-8 in CSF, collected at the University Hospitals of Geneva between 2010 and 2018, from patients diagnosed with GBS (n = 45) and with CIDP (n = 30) according to the Brighton and European Federation of Neurological Societies/Peripheral Nerve Society criteria by a physician blinded to biological results. CSF IL-8 was higher in GBS (median: 83.9 pg/mL) than in CIDP (41.0 pg/mL) (p < 0.001). Receiver operating characteristic analyses indicated that the optimal IL-8 cutoff was 70 pg/mL. Above this value, patients were more likely to present GBS than CIDP (specificity 96.7%, sensitivity 64.4%, positive predictive value [PPV] 96.7%, and negative predictive value [NPV] 64.4%). Among GBS subcategories, IL-8 was higher in acute inflammatory demyelinating polyneuropathy (AIDP, median: 101.8 pg/mL) than in other GBS variants (median: 53.7 pg/mL). In addition, with CSF IL-8 above 70 pg/mL, patients were more likely to present AIDP than acute-onset CIDP (p < 0.001; specificity 100%, sensitivity 78.8%, PPV 100%, and NPV 46.2%) or other CIDP with nonacute presentation (p < 0.0001; specificity 95.8%, sensitivity 78.8%, PPV 96.3%, and NPV 76.7%). CSF IL-8 levels can help to differentiate AIDP variant of GBS from CIDP, including acute-onset CIDP, with high specificity and PPV. This may improve early and appropriate treatment. This study provides Class II evidence that CSF IL-8 levels accurately distinguish patients with GBS from those with CIDP.


Giant intraosseous lipoma of the rib.
Lipoma is defined as a benign tumor consisting of a circumscribed mass of adipose tissue. Intraosseous lipomas represent fewer than 0.08% of all primary bone tumors. We present an unusual case of intraosseous lipoma arising from the left 10th and 11th ribs and extending to the subdiaphragmatic area and abdomen. Lipoma of the rib is an extremely rare disorder presenting diagnostic challenges.


Lessons from Israel's COVID-19 Green Pass program.
As of the beginning of March 2021, Israeli law requires the presentation of a Green Pass as a precondition for entering certain businesses and public spheres. Entitlement for a Green Pass is granted to Israelis who have been vaccinated with two doses of COVID-19 vaccine, who have recovered from COVID-19, or who are participating in a clinical trial for vaccine development in Israel. The Green Pass is essential for retaining immune individuals' freedom of movement and for promoting the public interest in reopening the economic, educational, and cultural spheres of activity. Nonetheless, and as the Green Pass imposes restrictions on the movement of individuals who had not been vaccinated or who had not recovered, it is not consonant with solidarity and trust building. Implementing the Green Pass provision while advancing its effectiveness on the one hand, and safeguarding equality, proportionality, and fairness on the other hand may imbue this measure with ethical legitimacy despite involving a potential breach of trust and solidarity.


Systemic antibiotics for treating diabetic foot infections.
Foot infection is the most common cause of non-traumatic amputation in people with diabetes. Most diabetic foot infections (DFIs) require systemic antibiotic therapy and the initial choice is usually empirical. Although there are many antibiotics available, uncertainty exists about which is the best for treating DFIs. To determine the effects and safety of systemic antibiotics in the treatment of DFIs compared with other systemic antibiotics, topical foot care or placebo. In April 2015 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library); Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE, and EBSCO CINAHL. We also searched in the Database of Abstracts of Reviews of Effects (DARE; The Cochrane Library), the Health Technology Assessment database (HTA; The Cochrane Library), the National Health Service Economic Evaluation Database (NHS-EED; The Cochrane Library), unpublished literature in OpenSIGLE and ProQuest Dissertations and on-going trials registers. Randomised controlled trials (RCTs) evaluating the effects of systemic antibiotics (oral or parenteral) in people with a DFI. Primary outcomes were clinical resolution of the infection, time to its resolution, complications and adverse effects. Two review authors independently selected studies, assessed the risk of bias, and extracted data. Risk ratios (RR) were estimated for dichotomous data and, when sufficient numbers of comparable trials were available, trials were pooled in a meta-analysis. We included 20 trials with 3791 participants. Studies were heterogenous in study design, population, antibiotic regimens, and outcomes. We grouped the sixteen different antibiotic agents studied into six categories: 1) anti-pseudomonal penicillins (three trials); 2) broad-spectrum penicillins (one trial); 3) cephalosporins (two trials); 4) carbapenems (four trials); 5) fluoroquinolones (six trials); 6) other antibiotics (four trials).Only 9 of the 20 trials protected against detection bias with blinded outcome assessment. Only one-third of the trials provided enough information to enable a judgement about whether the randomisation sequence was adequately concealed. Eighteen out of 20 trials received funding from pharmaceutical industry-sponsors.The included studies reported the following findings for clinical resolution of infection: there is evidence from one large trial at low risk of bias that patients receiving ertapenem with or without vancomycin are more likely to have resolution of their foot infection than those receiving tigecycline (RR 0.92, 95% confidence interval (CI) 0.85 to 0.99; 955 participants). It is unclear if there is a difference in rates of clinical resolution of infection between: 1) two alternative anti-pseudomonal penicillins (one trial); 2) an anti-pseudomonal penicillin and a broad-spectrum penicillin (one trial) or a carbapenem (one trial); 3) a broad-spectrum penicillin and a second-generation cephalosporin (one trial); 4) cephalosporins and other beta-lactam antibiotics (two trials); 5) carbapenems and anti-pseudomonal penicillins or broad-spectrum penicillins (four trials); 6) fluoroquinolones and anti-pseudomonal penicillins (four trials) or broad-spectrum penicillins (two trials); 7) daptomycin and vancomycin (one trial); 8) linezolid and a combination of aminopenicillins and beta-lactamase inhibitors (one trial); and 9) clindamycin and cephalexin (one trial).Carbapenems combined with anti-pseudomonal agents produced fewer adverse effects than anti-pseudomonal penicillins (RR 0.27, 95% CI 0.09 to 0.84; 1 trial). An additional trial did not find significant differences in the rate of adverse events between a carbapenem alone and an anti-pseudomonal penicillin, but the rate of diarrhoea was lower for participants treated with a carbapenem (RR 0.58, 95% CI 0.36 to 0.93; 1 trial). Daptomycin produced fewer adverse effects than vancomycin or other semi-synthetic penicillins (RR 0.61, 95%CI 0.39 to 0.94; 1 trial). Linezolid produced more adverse effects than ampicillin-sulbactam (RR 2.66; 95% CI 1.49 to 4.73; 1 trial), as did tigecycline compared to ertapenem with or without vancomycin (RR 1.47, 95% CI 1.34 to 1.60; 1 trial). There was no evidence of a difference in safety for the other comparisons. The evidence for the relative effects of different systemic antibiotics for the treatment of foot infections in diabetes is very heterogeneous and generally at unclear or high risk of bias. Consequently it is not clear if any one systemic antibiotic treatment is better than others in resolving infection or in terms of safety. One non-inferiority trial suggested that ertapenem with or without vancomycin is more effective in achieving clinical resolution of infection than tigecycline. Otherwise the relative effects of different antibiotics are unclear. The quality of the evidence is low due to limitations in the design of the included trials and important differences between them in terms of the diversity of antibiotics assessed, duration of treatments, and time points at which outcomes were assessed. Any further studies in this area should have a blinded assessment of outcomes, use standardised criteria to classify severity of infection, define clear outcome measures, and establish the duration of treatment.


Uncommon configuration of intercostobrachial nerves, lateral roots, and absent medial cutaneous nerve of arm in a cadaveric study.
The intercostobrachial nerve (ICBN) originates from the second intercostal nerve's lateral cutaneous branch, while the median nerve (MN) typically arises from the brachial plexus's lateral and medial roots. The medial cutaneous nerve of the arm, a branch of the medial cord of the brachial plexus, often connects with the ICBN. Variations were observed during the dissection of a 50-year-old male cadaver, including MN having two lateral roots (LR), LR1 and LR2, joining at different levels. Three ICBNs innervated the arm in this case, with the absence of the medial cutaneous nerve of the arm compensated by branches from the medial cutaneous nerve of the forearm. Understanding these anatomical variations is crucial for surgical procedures like brachioplasty, breast augmentation, axillary lymph node dissection, and orthopedic surgery. Surgeons and medical professionals must be aware of these variations to enhance preoperative planning, minimize complications, and improve patient outcomes in these procedures.


Timelines in the insect brain: fates of identified neural stem cells generating the central complex in the grasshopper Schistocerca gregaria.
This study employs labels for cell proliferation and cell death, as well as classical histology to examine the fates of all eight neural stem cells (neuroblasts) whose progeny generate the central complex of the grasshopper brain during embryogenesis. These neuroblasts delaminate from the neuroectoderm between 25 and 30 % of embryogenesis and form a linear array running from ventral (neuroblasts Z, Y, X, and W) to dorsal (neuroblasts 1-2, 1-3, 1-4, and 1-5) along the medial border of each protocerebral hemisphere. Their stereotypic location within the array, characteristic size, and nuclear morphologies, identify these neuroblasts up to about 70 % of embryogenesis after which cell shrinkage and shape changes render progressively more cells histologically unrecognizable. Molecular labels show all neuroblasts in the array are proliferative up to 70 % of embryogenesis, but subsequently first the more ventral cells (72-75 %), and then the dorsal ones (77-80 %), cease proliferation. By contrast, neuroblasts elsewhere in the brain and optic lobe remain proliferative. Apoptosis markers label the more ventral neuroblasts first (70-72 %), then the dorsal cells (77 %), and the absence of any labeling thereafter confirms that central complex neuroblasts have exited the cell cycle via programmed cell death. Our data reveal appearance, proliferation, and cell death proceeding as successive waves from ventral to dorsal along the array of neuroblasts. The resulting timelines offer a temporal blueprint for building the neuroarchitecture of the various modules of the central complex.


The Israeli law for the rehabilitation in the community of persons with psychiatric disabilities: Achievements and challenges.
The Community Rehabilitation of Persons with Mental Health Disability Law (2000a) is one of Israel's most important pieces of social legislation. It grants persons with psychiatric disabilities the right to receive rehabilitation in the community. This article is a case study of the development and implementation of a policy that led to the Rehabilitation Reform and that has become an important component in Israel's comprehensive mental health reform. The purpose of the study was to review and analyze the law and its elements, examine its implementation during its first two decades of operation, and to identify the issues it faces entering its third decade of application. The study examined the key components of the reform such as intended beneficiaries, financing, workforce, and services provided. It used Israel's official statistical data and drew upon a series of interviews with officials and experts on rehabilitation, mental health and social services. In 2020, 30,000 persons were receiving community psychiatric rehabilitation services, constituting about one fifth of the estimated eligible population. In addition to the reform's achievements, this article also identifies a number of issues. Toward the end of the second decade, problems between the psychiatric Rehabilitation Unit and the mental health services became apparent. As the Rehabilitation Law enters its third decade, it is recommended to establish an independent committee of experts to examine needed modifications in light of the conclusions drawn about the first two decades of its implementation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Recurrent human 16p11.2 microdeletions in type I Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients in Chinese Han population.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a severe congenital malformation of the female genital tract, is a highly heterogeneous disease which has no clear etiology. Previous studies have suggested that copy number variations (CNVs) and single-gene mutations might contribute to the development of MRKH syndrome. In particular, deletions in 16p11.2, which are suggested to be involved in several congenital diseases, have been reported in Chinese type II MRKH patients and European MRKH patients. However, few CNVs including 16p11.2 microdeletions were identified in Chinese type I MRKH cases although it accounted for the majority of MRKH patients in China. Thus, we conducted a retrospective study to identify whether CNVs at human chromosome 16p11.2 are risk factors of type I MRKH syndrome in the Chinese Han population. We recruited 143 patients diagnosed with type I MRKH between 2012 and 2014. Five hundred unrelated Chinese without congenital malformation were enrolled in control group, consisting of 197 from the 1000 Genomes Project and 303 from Fudan University. Quantitative PCR, array comparative genomic hybridization, and sanger sequencing were conducted to screen and verify candidate variant. Our study identified recurrent 16p11.2 microdeletions of approximately 600 kb in two out of the 143 type I MRKH syndrome patients using high-density array-based comparative genomic hybridization (aCGH), while no 16p11.2 deletion was found in the control group. We did not find any mutations in TBX6 gene in our samples. The results of the study identify 16p11.2 deletion in Chinese MRKH I patients for the first time, as well as support the contention that 16p11.2 microdeletions are associated with MRKH syndrome in both types across populations. It is suggested that 16p11.2 microdeletions should be included in molecular diagnosis and genetic counseling of female reproductive tract disorders.


[Inflammatory lung pseudotumor].
We report a 63 years old man presenting with a history of persistent cough and blood streaked sputum. Chest X rays and CAT scans showed a tumoral lesion between the superior and inferior right lobes. The tumor was resected and its pathological examination revealed an inflammatory pseudotumor. It is concluded that this type of tumors must be born in mind in patients with nodular lesions of the lung.


Quantum critical Kondo quasiparticles probed by ESR in β-YbAlB₄.
Electron spin resonance (ESR) can probe conduction electrons (CE) and local moment (LM) spin systems in different materials. A CE spin resonance (CESR) is observed in metallic systems based on light elements or with enhanced Pauli susceptibility. LM ESR can be seen in compounds with paramagnetic ions and localized d or f electrons. Here we report a remarkable and unprecedented ESR signal in the heavy-fermion superconductor β-YbAlB₄ [S. Nakatsuji et al., Nature Phys. 4, 603 (2008)] which behaves as a CESR at high temperatures and acquires characteristics of the Yb³⁺ LM ESR at low temperature. This dual behavior strikes as an in situ unique observation of the Kondo quasiparticles in a quantum critical regime. The proximity to a quantum critical point may favor the appearance of this dual character of the ESR signal in β-YbAlB₄.


MRI of articular cartilage in OA: novel pulse sequences and compositional/functional markers.
Osteoarthritis (OA) is a leading cause of disability worldwide. Magnetic resonance imaging (MRI), with its unique ability to image and characterize soft tissue non-invasively, has proven valuable in assessing cartilage in OA. The development of new, fast imaging methods with high contrast show promise to improve the magnetic resonance (MR) evaluation of this disease. In addition to morphologic MRI methods, MRI contrast mechanisms under development may reveal detailed information about the physiology of cartilage. It is anticipated that these and other MRI techniques will play an increasingly important role in assessing the success or failure of therapies for OA. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) held a workshop in Bethesda, MD aiming at providing a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies in the use of MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to novel MRI pulse sequences for evaluating articular cartilage of the knee in OA and notes any additional advances that have been made since.


Evaluation of potential organ culture media for eye banking using a human corneal endothelial cell growth assay.
To evaluate the ability of different commercially available cell culture media to induce proliferation and morphological changes in primary cultures of human corneal endothelial cells (HCEC). This screening model was used in an attempt to establish a rational basis for the development of well-defined, serum-free preservation media for long-term organ culture of human donor corneas. A total of 11 different culture media enriched with 0%, 2%, 5%, and 10% fetal calf serum (FCS) were compared. The test media were divided into three groups: Group 1: Media based on minimal essential medium (MEM), currently used for long-term corneal organ culture in European eye banks; Group 2: F99-based media, enriched for growth of corneal endothelial cells at serum-reduced conditions; and Group 3: Media designed for growth of special cell types or for short-term corneal organ culture. The growth-promoting capacity of each test medium was quantified using an HCEC proliferation assay, whereas changes in cell morphology were evaluated by phase-contrast microscopy. The morphological characteristics of HCEC were best maintained in the group of F99-based media, which also induced the highest level of cell proliferation under serum-reduced conditions. Specifically, the medium F99-Sr (F99 enriched with ascorbic acid, insulin, bFGF, transferrin, selenium, and lipids) induced a two- to three-fold higher HCEC density at both 0% and 2% FCS when compared to all other test media, and it also maintained the most endothelial cell-like morphology. Also, at higher serum concentrations (5% and 10% FCS), the cell growth was most prominent in F99-Sr, as well as in the medium SFM that originally was designed for serum-free growth of vascular endothelial cells. This study suggests that the media F99-Sr and SFM should be further tested and refined as potential new storage solutions for long-term corneal organ culture at physiological temperatures.


Perfluorooctane sulfonate (PFOS) distribution and effect factors in the water and sediment of the Yellow River Estuary, China.
The distribution of perfluorooctane sulfonate (PFOS) was investigated in a total of 15 water and sediment samples from the Yellow River Estuary, China in April 2011. The results indicated that the concentrations of PFOS in the water and sediment samples averaged 157.5 ng/L and 198.8 ng/g and ranged from 82.30 to 261.8 ng/L and 75.48 to 457.0 ng/g, respectively. The concentrations of PFOS in the sediment column increased from 45.32 to 379.98 ng/g with the decrease of the sampling depth, which showed that the increased PFOS pollution in the sediment appeared in this region in over recent years. The distribution coefficient (K d) of PFOS between water and sediment linearly increased from 0.37 to 4.80 L/g as the salinity (S‰) increased from 0.18 to 4.47. Correlation analysis revealed that K d was significantly and positively correlated to the contents of total organic carbon and clay of the sediment, and salinity. Therefore, salinity was an important parameter in controlling the sediment-water interactions and the fate or transport of PFOS in the aquatic environment. The results of this study showed that the estuary was an important sink for PFOS and suggested that PFOS might be carried with the river water and transported for long distances before it reached to the sea and largely scavenged to the sediment in the estuaries due to the change in salinity.


COVID-19 cases and testing in 53 prison systems.
COVID-19 has entered United States prison systems at alarming rates. Disparities in social and structural determinants of health disproportionately affect those experiencing incarceration, making them more vulnerable to COVID-19. Additionally, prisons are sites of congregate living, making it impossible to practice social distancing, and most prisons have relied only on incremental measures to reduce risk and spread of COVID-19. To more fully understand the impact that COVID-19 is having on incarcerated populations, it is critical to have systematic data on testing, test positivity, cases, and case fatality. Using data from the COVID Prison Project, we present data on 53 prison systems COVID-19 testing, test positivity, case, and case fatality by state and compare these data with each state's general population. We do this for the early stages of the pandemic, utilizing data through July 15, 2020. Many states are not reporting full information on COVID testing with some also not reporting on case fatality. Among those reporting data, there is a wide variation between testing, test positivity, and case rates within prison systems and as compared to the general population. However, when more tests are deployed more cases are identified with the majority of state prisons having higher case rates than their general population. These findings underscore the need for the implementation and study of COVID-19 mitigation and surveillance strategies to flatten the COVID-19 curve in prisons across the country. We call for future research to build on these data from the COVID Prison Project to protect the health of our nations' often forgotten residents.


Readmission rates of South Korean psychiatric inpatients by inpatient volumes per psychiatrist.
Readmission rates of psychiatric inpatients are higher in South Korea than other Organization for Economic Co-operation and Development (OECD) countries. In addition, the solution for readmission control is deficient based on the characteristics of the South Korean National Health Insurance (NHI) system. Therefore, it is necessary to identify ways to reduce psychiatric inpatient readmissions. This study investigated the relationship between inpatient volume per psychiatrist and the readmission rate of psychiatric inpatients in South Korea. We used NHI claim data (N = 37,796) from 53 hospitals to analyze readmission within 30 days for five diagnosis (organic mental disorders, mental and behavioral disorders due to psychoactive substance use, schizophrenia, mood disorders, neurotic disorders, and stress-related and somatoform disorders) between 2010 and 2013. We performed χ2 and analysis of variance tests to investigate associations between patient and hospital-level variables and readmission within 30 days. Finally, generalized estimating equation (GEE) models were analyzed to examine possible associations with readmission. Readmissions within 30 days accounted for 1,598 (4.5 %) claims. Multilevel analysis demonstrated that inpatient volume per psychiatrist were inversely related with readmission within 30 days (low odds ratio [OR]: 0.38, 95 % confidence interval [CI]: 0.28-0.51; mid-low OR: 0.48, 95 % CI: 0.36-0.63; mid-high OR: 0.55, 95 % CI: 0.44-0.69; Q4 = ref). The subgroup analysis by diagnosis revealed that both "schizophrenia, schizotypal, and delusional disorders" and "mood disorders" had inverse relationships with readmission risk for all volume groups. We observed an inverse association between inpatient volume per psychiatrist and the 30-day readmission rate of psychiatric inpatients, suggesting that it could be a useful quality indicator in mental health care.


The evidence for soybean products as cancer preventive agents.
There is much evidence suggesting that compounds present in soybeans can prevent cancer in many different organ systems. The evidence for specific soybean-derived compounds having a suppressive effect on carcinogenesis in animal model systems is limited, however. There is evidence that the following isolated soybean derived products suppress carcinogenesis in vivo: a protease inhibitor, the Bowman-Birk inhibitor, inositol hexaphosphate (phytic acid) and the sterol beta-sitosterol. Other compounds that may be able to suppress carcinogenesis in animals are the soybean isoflavones. Soybean compounds reported to have other types of anticarcinogenic activity include soybean trypsin inhibitor, saponins and genistein. There is much evidence to suggest that diets containing large amounts of soybean products are associated with overall low cancer mortality rates, particularly for cancers of the colon, breast and prostate. It is believed that supplementation of human diets with certain soybean products shown to suppress carcinogenesis in animals could markedly reduce human cancer mortality rates.


Out of Rhythm: Compromised Precision of Theta-Gamma Coupling Impairs Associative Memory in Old Age.
Episodic memory declines with advancing adult age. This decline is particularly pronounced when associations between items and their contexts need to be formed. According to theories of neural communication, the precise coupling of gamma power to the phase of the theta rhythm supports associative memory formation. To investigate whether age differences in associative memory are related to compromised theta-gamma coupling, we took EEG recordings during the encoding phase of an item-context association task. Fifty-eight younger (33 females) and 55 older (24 females) adults studied pictures of objects superimposed on background scenes. In a recognition test, objects were presented on old or new backgrounds, and participants responded if they had seen (1) the object and (2) the object/scene pair. Theta-gamma coupling supported pair memory formation in both age groups. Whereas pair memory was associated with coupling closer to the peak of the theta rhythm, item-only memory was associated with a deviation in phase angle relative to pair memory. Furthermore, a stable relation between coupling phase and pair memory performance demonstrated that coupling closer to the peak is beneficial for associative memory. Critically, older adults' lower pair memory was accompanied by a shift in coupling phase relative to that of younger adults. In concert, the present results are consistent with the hypothesis that decrements in the temporal precision with which gamma power is coupled to a specific theta phase underlie the decline of associative memory in normal cognitive aging.SIGNIFICANCE STATEMENT According to prominent theories of neural communication, the precise coordination of oscillatory activity enables the formation of associative memories. We propose that normal cognitive aging impairs associative memory formation by compromising the temporal precision of neural communication. We show that the coupling of high-frequency gamma power to low-frequency theta phase supports associative memory formation in both younger and older adults, with coupling closer to the theta peak benefitting memory performance. However, compared with younger adults, the coupling phase angle is shifted in time and is more variable in the older adults. We conclude that alterations in the precise timing of theta-gamma coupling contribute to adult age differences in associative memory.


Takayasu arteritis: challenges in diagnosis and management.
Takayasu arteritis (TA) is a rare disease affecting chiefly young women, although it can affect both men and women and persons of many different ethnicities. TA carries a high morbidity rate, but importantly, overall mortality has declined over time such that the 15-year survival rate has increased from 82.9% for patients diagnosed between 1957 and 1975 to 96.5% for those diagnosed from 1976 to 1990. Severity of presenting arterial complications and delay to diagnosis have also decreased over the past decade owing to advances in non-invasive diagnostic imaging and the development of medical therapies. Despite these advances, there still remain significant gaps in the diagnosis and management of these complex patients. These gaps encompass the basic, yet extremely complex, tasks of defining a universally accepted diagnostic criterion, accurate assessment of disease activity and development of clinically meaningful and accurate outcome measures to guide necessary clinical trials for the management of these complex patients.


[Operable breast cancer without axillary node involvement: current therapeutic concepts].
Although the majority of women with node-negative breast cancer will be disease-free at 10 years, 25 to 30 percent will have a recurrence and die from their disease. Therapeutic concepts for these patients are changing rapidly as a result of recently published randomized clinical trials showing a small but significant disease-free survival advantage at 4 years when adjuvant chemo- or hormonal therapy is given following surgery. This paper reviews these important trials as well as the literature pertaining to potentially new prognostic factors capable of selecting from the entire population of node-negative patients those who are truly at risk of relapsing and who are most likely to benefit from adjuvant therapy. Issues such as treatment toxicity and future directions for clinical research are also briefly discussed.


Extra-cardiac and complex Fontan baffle fenestration using radio frequency current via surgical electrocautery.
Fontan baffle punctures and creation of Fontan fenestration for cardiac catheterisation procedures remain challenging especially due to the heavy calcification of prosthetic material and complex anatomy. We sought to evaluate our experience using radiofrequency current via surgical electrocautery needle for Fontan baffle puncture to facilitate diagnostic, electrophysiology, and interventional procedures. A retrospective chart review of all Fontan patients (pts) who underwent Fontan baffle puncture using radiofrequency energy via surgical electrocautery from three centres were performed from January 2011 to July 2021. A total of 19 pts underwent 22 successful Fontan baffle puncture. The median age and weight were 17 (3-36 years) and 55 (14-88) kg, respectively. The procedural indications for Fontan fenestration creation included: diagnostic study (n = 1), atrial septostomy and stenting (n = 1), electrophysiology study and ablation procedures (n = 8), Fontan baffle stenting for Fontan failure including protein-losing enteropathy (n = 7), and occlusion of veno-venous collaterals (n = 2) for cyanosis. The type of Fontan baffles included: extra-cardiac conduits (n = 12), lateral tunnel (n = 5), classic atrio-pulmonary connection (n = 1), and intra-cardiac baffle (n = 1). A Fontan baffle puncture was initially attempted using traditional method in 6 pts and Baylis radiofrequency trans-septal system in 2 pts unsuccessfully. In all pts, Fontan baffle puncture using radiofrequency energy via electrocautery needle was successful. The radiofrequency energy utilised was (10-50 W) and required 1-5 attempts for 2-5 seconds. There were no vascular or neurological complications. Radiofrequency current delivery using surgical electrocautery facilitates Fontan baffle puncture in patients with complex and calcified Fontan baffles for diagnostic, interventional, and electrophysiology procedures.


Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence.
Cellular senescence acts as a potent barrier for tumour initiation and progression. Previous studies showed that the PML tumour suppressor promotes senescence, although the precise mechanisms remain to be elucidated. Combining gene expression profiling with chromatin-binding analyses and promoter reporter studies, we identify TBX2, a T-box transcription factor frequently overexpressed in cancer, as a novel and direct PML-repressible E2F-target gene in senescence but not quiescence. Recruitment of PML to the TBX2 promoter is dependent on a functional p130/E2F4 repressor complex ultimately implementing a transcriptionally inactive chromatin environment at the TBX2 promoter. TBX2 repression actively contributes to senescence induction as cells depleted for TBX2 trigger PML pro-senescence function(s) and enter senescence. Reciprocally, elevated TBX2 levels antagonize PML pro-senescence function through direct protein-protein interaction. Collectively, our findings indicate that PML and TBX2 act in an autoregulatory loop to control the effective execution of the senescence program.


Topoisomerase IV can support oriC DNA replication in vitro.
Escherichia coli has two type II topoisomerases, DNA gyrase and topoisomerase IV (Topo IV). Topo IV is required for the decatenation of the linked daughter chromosomes at the terminal stages of DNA replication, whereas gyrase, because of its ability to convert to negative supercoils the positive supercoils generated by replication fork progression in a circular chromosome, is required to support nascent chain elongation. Using an oriC DNA replication system in vitro, we show that Topo IV, which can relax positive supercoils, can also support replication fork progression. This activity is only observed at substoichiometric ratios of Topo IV to template, at higher ratios, the template becomes relaxed and initiation of DNA replication cannot occur. Topo IV was capable of supporting bidirectional DNA replication from oriC, although, unlike the case with gyrase, some templates apparently replicated unidirectionally. This suggests that either gyrase itself or a certain minimum superhelical density is required for proper initiation of DNA replication from oriC.


Modulation of protein composition of nuclear lamina. Reduction of lamins B1 and B2 in livers of griseofulvin-treated mice.
Chronic griseofulvin (GF) intoxication of mice leads to severe alterations of the hepatocytic intermediate filament cytoskeleton similar to that found in alcoholic hepatitis in humans (i.e., derangement and diminution of the keratin filament network and appearance of cytoplasmic aggregates of keratin-containing material, termed Mallory bodies). To investigate eventual alterations of nuclear lamins under these pathologic situations monoclonal antibodies were produced. One of these, GL-35, was directed to lamin B1 and lamin B2. Immunofluorescence microscopy revealed in GF-treated livers, in comparison to normal mouse livers, a highly reduced immunoreaction for lamins B1 and B2, whereas the staining for lamins A and C was unchanged. This reduction of both B-type lamins occurred before detectable alterations of keratin filaments and was reversible after cessation of GF intoxication. A diminished content of both B-type lamins in relation to lamins A and C in GF-intoxicated livers was also revealed by analysis of isolated nuclear envelopes on two-dimensional gels. Moreover, there was a clear predominance of more acidic isoelectric variants of lamins B1 and B2. In contrast to the reduced amount of B-type lamin proteins no reduction in the concentration of the mRNA for lamin B1 was found. For lamin B2 even an increase of mRNA was detected in GF-treated livers. These results indicate that GF not only interferes with expression of the keratin intermediate filament skeleton of hepatocytes but also leads to selective alterations of the nuclear lamins, most likely by posttranslational modifications of intermediate filament proteins.


Post prostatectomy urinary incontinence.
The specific incidence rate of post prostatectomy incontinence is difficult to ascertain. However, regardless of the type of prostatectomy, whether it be transurethral, radical retropubic or radical perineal prostatectomy, or the nature of the prostatic disease, several risk factors are common to all. The most significant risk factors include pre-existing detrusor and/or sphincter dysfunction, increasing age, and surgical expertise. Management options include behavioral techniques, pharmacologic therapy, surgical intervention, and other supportive measures. While no definitive preventive measures can be recommended at this time, reducing the incidence of post prostatectomy urinary incontinence should be the goal.


[Transvaginal echography in the diagnosis of endometrioid cysts of the ovaries].
Research into the value of transvaginal echography in the diagnosis of endometrioid ovarian cysts has shown that this pathology is characterized by the presence of a round or oblong formation, filled with small-dotted suspension of mean or high echogeneity, by a dense hyperechogenic component of small sizes and wall thickening up to 0.2-0.3 cm. The accuracy of diagnosis of endometrioid ovarian cysts was 92.3%.


A two-edged role for the transposable element Kiddo in the rice ubiquitin2 promoter.
Miniature inverted repeat transposable elements (MITEs) are thought to be a driving force for genome evolution. Although numerous MITEs are found associated with genes, little is known about their function in gene regulation. Whereas the rice ubiquitin2 (rubq2) promoter in rice (Oryza sativa) line IR24 contains two nested MITEs (Kiddo and MDM1), that in line T309 has lost Kiddo, providing an opportunity to understand the role of MITEs in promoter function. No difference in endogenous rubq2 transcript levels between T309 and IR24 was evident using RT-PCR. However, promoter analysis using both transient and stably transformed calli revealed that Kiddo contributed some 20% of the total expression. Bisulfite genomic sequencing of the rubq2 promoters revealed specific DNA methylation at both symmetric and asymmetric cytosine residues on the MITE sequences, possibly induced by low levels of homologous transcripts. When methylation of the MITEs was blocked by 5-azacytidine treatment, a threefold increase in the endogenous rubq2 transcript level was detected in IR24 compared with that in T309. Together with the observed MITE methylation pattern, the detection of low levels of transcripts, but not small RNAs, corresponding to Kiddo and MDM1 suggested that RNA-dependent DNA methylation is induced by MITE transcripts. We conclude that, although Kiddo enhances transcription from the rubq2 promoter, this effect is mitigated by sequence-specific epigenetic modification.


Intraperitoneal Chemotherapy in Patients Pretreated for Ovarian Cancer Matched with Patients Treated with Parenteral Chemotherapy.
Our aim was to analyze the impact of intraperitoneal chemotherapy (IPC), administered with direct peritoneal puncture, on the survival of patients with pretreated ovarian cancer in a real-life setting. This was a retrospective study comparing patients with advanced ovarian cancer treated with IPC (N=33) and patients treated with standard intravenous (i.v.) chemotherapy matching cases for known prognostic factors (age, platinum sensitivity, histological subgroup and grade). Data were then analyzed for survival with nested Cox multivariate regression. The case matching resulted in two homogeneous cohorts by age, platinum sensitivity, resistance to therapy and histology. When analyzed by hazard ratio (HR), the number of previous treatments and IPC vs. i.v. therapy were significant (HR=1.97 for i.v. and HR=1.90 for each incremental previous treatment line, multivariate p<0.001). When analyzing the patients with fewer than three previous treatment lines, IPC conferred a survival advantage of about 2.2 months (IPC=10.0 vs. i.v.=7.8 months, p=0.011). However, the survival advantage in heavily pre-treated patients (with three or more previous treatments) was not significant. One case, pre-treated with more lines of chemotherapy, with renal failure after intraperitoneal cisplatin was followed by death. None of the patients had bowel sub-occlusions and we recorded a lower incidence of local toxicity, such as cellulite, with IPC (two out of 33 cases). Two patients thereafter refused IPC due to abdominal pain. Our findings confirm that IPC is an effective approach compared to systemic chemotherapy for advanced ovarian cancer, even in pre-treated patients, including platinum-resistant cases. The survival benefit appears to be confined to non-heavily treated patients. Overall, direct intraperitoneal drug injection (without permanent devices) appears to be feasible, safe and possibly advantageous.


[A Case of Locally Advanced, Unresectable Pancreatic Cancer with Superior Mesenteric Artery Invasion Treated with FOLFIRINOX plus Radiation Therapy, followed by Conversion Surgery].
We report a case of a woman in her 70s who underwent conversion surgery after FOLFIRINOX, followed by radiation therapy for initially locally advanced unresectable pancreatic cancer. She visited her local doctor with a chief complaint of upper abdominal pain. Contrast-enhanced CT scan of the abdomen revealed an irregular mass invading the superior mesenteric artery, and the first and second jejunal arteries(>180°)in the pancreatic uncinate region. Based on imaging, she was diagnosed as UR-LA(sm), cT4N0M0, cStage Ⅲ pancreatic cancer, and underwent 5 courses of modified FOLFIRINOX. Radiation therapy of 50.4 Gy was added for local control, and CA19-9 decreased from 394.1 U/mL to 10.5 U/mL. The treatment effect was judged as RECIST: partial response. The tumor was considered to be potentially curative, and a subtotal stomach preserving pancreaticoduodenectomy was performed 8 months after the initial treatment. The tumor was found to be 3× 2 mm in size, pStage ⅠA, R0, and the response to preoperative chemotherapy: Evans Grade Ⅲ. The patient is alive at 5 months postoperatively without recurrence.


Effects of Adding Different Levels of Hydroponic Barley Fodder on the Productive Performance and Economic Value of Broiler Chickens.
The present study was conducted to disclose the impact of adding different levels of hydroponic barley fodder (HBF) on some productive features of the economic value of broilers chickens. One hundred forty-four one-day-old Ross 308 chicks were used in this study. Birds were randomly distributed into four treatments, with three replicates per each treatment (12 birds per replicate): The first treatment had no addition (T1:control). As for T2 and T3 treatments, 10% and 20% of HBF were added to the feed pellet. In T4, fresh HBF was chopped and fed as an additional free fodder. Results reflected an increase in the weekly live body weight (BW), body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) of T2 birds; along with an improvement in the cumulative BWG, FI, and FCR of T2 and T4 during the 3rd to 5th weeks compared with the other treatments. Bacteriology and gut morphology demonstrated a decrease in total fungi, bacteria, and E. coli count with an increase in Lactobacillus count, in conjunction with an increase in the villus height and crypt depth of the jejunum of T2 birds. Economic value measures showed an increase in the production index and economic marker for broilers treated with T2 and T4. It can be concluded that there is an opportunity to include HBF by 10% or present it as freshly chopped HBF to ameliorate production performance, improve economic indicators and reduce broiler production costs by 9%.


A case of cerebrotendinous xanthomatosis with massive xanthomas but without a considerable increase in serum cholestanol levels.
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by mutations in the sterol 27-hydroxylase gene (CYP27A1). Due to the deficiency of 27-hydroxylase, the synthesis of bile acids from cholesterol is impaired and excessive cholestanol accumulates in various tissues, such as the central nervous system, tendons, and lenses. Patients with CTX typically manifest intellectual decline, pyramidal tract symptoms, cerebellar symptoms, tendon xanthomas, juvenile cataracts, neonatal jaundice, chronic diarrhea, osteoporosis, and premature cardiovascular disease. Here, we report the atypical case of a 35-year-old female with CTX having massive xanthomas but without a considerable increase in serum cholestanol levels (3.9 µg/mL). In the differential diagnosis of xanthoma, CTX should not be ruled out even if the serum levels of cholestanol are not high, and genetic testing is necessary to make the appropriate diagnosis.


Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis.
There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis. A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modeling was conducted using Pmetrics. Nine patients were recruited, and a two-compartment model adequately described the data. The piperacillin clearance (CL), volume of distribution of the central compartment (Vc), and distribution rate constants from the central to the peripheral compartment and from the peripheral to the central compartment were 5.6 ± 3.2 liters/h, 14.5 ± 6.6 liters, 1.5 ± 0.4 h-1, and 1.8 ± 0.9 h-1, respectively, where CL and Vc were found to be described by creatinine clearance (CLCR) and total body weight, respectively. In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CLCR was found to be the most important determinant of piperacillin pharmacokinetics.


Characterization of calcium carbonate polymorphs with Ca K edge X-ray absorption fine structure spectroscopy.
Ca K edge X-ray absorption fine structure (XAFS) spectroscopy was utilized for the characterization and quantification of calcium carbonate polymorphs and their mixtures. The advantage of the XAFS is the small sample quantity required for measurements, and a flexible sample environment. The near-edge XAFS spectra of calcite, aragonite and vaterite were measured with the conversion electron yield (CEY) method, and the obtained spectra showed characteristic features that can be utilized as fingerprints. The quantification of mixed polymorphs was examined by using a linear combination fitting of reference XAFS spectra. Though the quality of the fits was satisfactory, discrepancies in the evaluated values were observed between those with X-ray diffraction (XRD) and XAFS. The nonuniformity of samples may be enhanced by the surface sensitivity of the CEY method.


Curb the spread: Leveraging intensive longitudinal data to unravel within- and between-person processes in adherence to nonpharmaceutical interventions during COVID-19.
Adhering to behavioral recommendations and nonpharmaceutical interventions (NPIs) is a key to control COVID-19 infection rates. However, rates have decreased globally, and potentially modifiable determinants of ongoing adherence and their interaction with social and physical momentary environments are still poorly understood. Here, we comprehensively examine within-person variations and between-person differences in known behavioral determinants (capability and motivation), as well as the moderating role of situational variable environmental factors (opportunity) in predicting adherence to hygiene and social distancing behaviors. Ecological momentary assessment study over 6 months with monthly assessment bouts (4 days each and five daily assessments) in 623 German adults. Repeated daily assessments of capability, opportunity, motivation, and behavior (COM-B) model factors. Bayesian multilevel logistic regression models were estimated to examine main effects of COM-B factors and moderating effects of momentary environmental factors. Momentary adherence to NPIs was predicted by within-person changes in COM-B factors (motivation: intentions, goal conflict, and control beliefs; opportunities: regulations and norms). Between-person differences in capabilities (habit strength) and motivation (intentions and control beliefs) predicted adherence across situations. Situation-specific environmental factors moderated the motivation-behavior association (regulation measures increased; goal conflict and nonadherent others decreased the association). Individual momentary (within-person) and stable (between-person) motivation indicators predicted adherence. However, situational environmental factors such as regulations or norms have strong main effects and moderate the motivation-behavior translation. These findings have policy implications, supporting recent claims to not rely on the narrative of "personal responsibility," but instead combine health education measures to increase individual motivation with consistent regulation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Fluorescence detection, enumeration and characterization of single circulating cells in vivo: technology, applications and future prospects.
There are many diseases and biological processes that involve circulating cells in the bloodstream, such as cancer metastasis, immunology, reproductive medicine, and stem cell therapies. This has driven significant interest in new technologies for the study of circulating cells in small animal research models and clinically. Most currently used methods require drawing and enriching blood samples from the body, but these suffer from a number of limitations. In contrast, 'in vivo flow cytometry' (IVFC) refers to set of technologies that allow study of cells directly in the bloodstream of the organism in vivo. In recent years the IVFC field has grown significantly and new techniques have been developed, including fluorescence microscopy, multi-photon, photo-acoustic, and diffuse fluorescence IVFC. In this paper we review recent technical advances in IVFC, with emphasis on instrumentation, contrast mechanisms, and detection sensitivity. We also describe key applications in biomedical research, including cancer research and immunology. Last, we discuss future directions for IVFC, as well as prospects for broader adoption by the biomedical research community and translation to humans clinically.


A cross-sectional study to evaluate hypovitaminosis C prevalence and risk factors in an acute geriatric unit in Lyon, France: the HYPO-VIT-C protocol.
Vitamin C is an essential micronutrient playing crucial roles in human biology. Hypovitaminosis C is defined by a plasmatic ascorbemia below 23 µmol/L and is associated with numerous outcomes such as cardiovascular diseases, cancers or neurocognitive disorders. Numerous risk factors are common among older adults making them particularly susceptible to hypovitaminosis C. These risk factors include reduced vitamin intakes, higher vitamin metabolism related to polypathology, and iatrogeny because of polypharmacy. However, the precise prevalence of hypovitaminosis C and its risk factors are poorly documented within the geriatric population.A better knowledge of hypovitaminosis C prevalence and risk factor may lead to improving the vitamin C status among older people and prevent its consequences. To answer these questions, we designed a monocentric cross-sectional study in a population of older hospitalised patients in Lyon, France. A sample size of 385 patients was needed to estimate hypovitaminosis C prevalence. The study was proposed to all eligible patient aged more than 75 years old entering the participating acute geriatric unit. The plasmatic vitamin C status was systematically assessed for participating patients, and variables part of the medical and geriatric evaluation were collected. For patients with severe vitamin C depletion, an oral supplementation and a follow-up phone call were organised to ensure treatment completion and tolerance. The protocol has been approved by an independent national ethics committee and meets the methodological requirements. Final outcomes will be published in a peer-reviewed journal and disseminated through conferences. NCT05668663.


Mice with targeted mutations of glucocorticoid and mineralocorticoid receptors: models for depression and anxiety?
Impaired corticosteroid receptor signaling is a key mechanism in the pathogenesis of stress-related psychiatric disorders such as depression and anxiety. Since in vivo expression and functional studies of corticosteroid receptors are not feasible in the human central nervous system, such analyses have to be done in animal models. Transgenic mice with mutations of corticosteroid receptors are promising tools, which allow us to investigate the role of these proteins in the pathogenesis of symptoms characteristic for depression and anxiety. This review summarizes the neuroendocrinological and behavioral findings that have been obtained in six different mouse strains with specific mutations that influence the expression or the function of the glucocorticoid or the mineralocorticoid receptor (MR). The analyses of these mice helped to define molecular concepts of how corticosteroid receptors regulate the activity of the hypothalamic-pituitary-adrenal (HPA) system. Furthermore, some of these mutant mice exhibited characteristic alterations in behavioral tests for anxiety and despair. However, so far, none of the mouse strains described here can be viewed as an animal model of a specific psychiatric disease defined by common diagnostic criteria. Using high throughput technologies for the identification of genes regulated by glucocorticoid receptor (GR) and MR in brain areas responsible for specific symptoms of stress-related disorders will yield potential new drug targets for the treatment of depression and anxiety.


Attenuation of soft-tissue sarcomas resistance to the cytotoxic action of TNF-α by restoring p53 function.
Isolated limb perfusion with TNF-α and melphalan is used with remarkable efficiency to treat unresectable limb sarcomas. Here we tested the ability of TNF-α to directly induce apoptosis of sarcoma cells. In addition, we investigated the impact of p53 in the regulation of such effect. We first analysed the ability of TNF-α to induce apoptosis in freshly isolated tumour cells. For this purpose, sarcoma tumours (n = 8) treated ex vivo with TNF-α were processed for TUNEL staining. It revealed substantial endothelial cell apoptosis and levels of tumour cell apoptosis that varied from low to high. In order to investigate the role of p53 in TNF-α-induced cell death, human sarcoma cell lines (n = 9) with different TP53 and MDM2 status were studied for their sensitivity to TNF-α. TP53(Wt) cell lines were sensitive to TNF-α unless MDM2 was over-expressed. However, TP53(Mut) and TP53(Null) cell lines were resistant. TP53 suppression in TP53(Wt) cell lines abrogated TNF-α sensitivity and TP53 overexpression in TP53(Null) cell lines restored it. The use of small molecules that restore p53 activity, such as CP-31398 or Nutlin-3a, in association with TNF-α, potentiated the cell death of respectively TP53(Mut) and TP53(Wt)/MDM2(Ampl). In particular, CP-31398 was able to induce p53 as well as some of its apoptotic target genes in TP53(Mut) cells. In TP53(Wt)/MDM2(Ampl) cells, Nutlin-3a effects were associated with a decrease of TNF-α-induced NF-κB-DNA binding and correlated with a differential regulation of pro- and anti-apoptotic genes such as TP53BP2, GADD45, TGF-β1 and FAIM. More effective therapeutic approaches are critically needed for the treatment of unresectable limb sarcomas. Our results show that restoring p53 activity in sarcoma cells correlated with increased sensitivity to TNF-α, suggesting that this strategy may be an important determinant of TNF-α-based sarcomas treatment.


EGF receptor and p185erbB-2-specific single-chain antibody toxins differ in their cell-killing activity on tumor cells expressing both receptor proteins.
Many human tumors over-express erbB-2 and EGF receptors. The membrane localization of these receptor tyrosine kinases make them appropriate targets for directed tumor therapy. We have used recombinant DNA technology to produce single-chain antibody exotoxin A (scFv-ETA) fusion proteins which specifically bind the erbB-2 and EGF receptors. The scFv portion is composed of the heavy- and light-chain variable domains of monoclonal antibodies which recognize the extracellular portion of each receptor. We have previously described the anti-tumor activity of the bacterially produced scFv(FRP5)-ETA directed to the erbB-2 receptor. In this paper we describe the characteristics of scFv(225)-ETA, a protein which binds the EGF receptor. The bacterially produced recombinant protein binds to the receptor with high affinity and inhibits the in vitro growth of the EGF receptor over-expressing tumor cell lines A431 and MDA-MB468. Combination treatment with scFv-(FRP5)-ETA and scFv(225)-ETA led to an additive inhibitory effect on the in vitro growth of A431 cells. SKBR3 cells expressing low levels of EGF receptor but high levels of p185erbB-2 were not affected by scFv(225)-ETA treatment but were sensitive to scFv(FRP5)-ETA. Stimulation of SKBR3 cells and HCII RI#11 mouse mammary epithelial cells expressing the human erbB-2 with EGF led to an increase in scFv(FRP5)-ETA activity, showing that the EGF-induced activation of erbB-2 can potentiate the action of the erbB-2-directed toxin. Treatment of athymic nude mice with scFv(FRP5)-ETA and the combination of both scFv-ETA proteins led to the transient arrest of growth of established A431 tumors. scFv(225)-ETA treatment alone was the most effective, leading to tumor shrinkage during the course of treatment, whereas treatment with the parental monoclonal antibody 225 led to retarded tumor growth.


HHS Expands Rules for Clinical Trial Reporting.
The HHS and NIH have adopted new policies aimed at clarifying and expanding the reporting requirements for clinical trials and more quickly disseminating data to researchers and the public. Among the changes: requiring registration of trials that test experimental and early-stage therapies, and posting results for trials of unapproved drugs. The policies take effect January 18, 2017.


Is the European pediatric medicine regulation working for children and adolescents with cancer?
The European Pediatric Medicine Regulation was launched in 2007 to provide better medicines for children. Five years later, the number of new anticancer drugs in early development in the pediatric population remains low, and most children with cancer are still largely denied access to innovative drugs in Europe, as compared with the United States. We analyzed individual pediatric investigation plan (PIP) and waiver decisions for oncology drugs and all oncology drugs that have been approved for marketing authorization since 2007 in Europe. Among the 45 approved PIPs, 33% concern leukemias and lymphomas, 29% solid tumors, 13% brain tumors, and 20% a drug for supportive care. No specific PIP exists for life-threatening diseases such as high-risk neuroblastoma, whereas there are several PIPs in extremely rare malignancies in children and adolescents such as gastrointestinal stromal tumor, melanoma, thyroid cancer, and chronic myeloid leukemia. This paradoxical situation is due to approval of a PIP being driven by the adult indication. Twenty-six of 28 authorized new oncology drugs have a potentially relevant mechanism of action for pediatric malignancies, but 50% have been waived because the adult condition does not occur in children. The most striking example is crizotinib. Implementation of the pediatric regulation should no longer be driven by the adult indication but should be guided instead by the biology of pediatric tumors and the mechanism of action of a drug. This change will be achievable through voluntary PIPs submitted by Pharma or revocation of the oncology class waiver list.


What are effective strategies to respond to the psychological impacts of working on the frontlines of a public health emergency?
The COVID-19 pandemic has disrupted the healthcare and public health sectors. The impact of working on the frontlines as a healthcare or public health professional has been well documented. Healthcare organizations must support the psychological and mental health of those responding to future public health emergencies. This systematic review aims to identify effective interventions to support healthcare workers' mental health and wellbeing during and following a public health emergency. Eight scientific databases were searched from inception to 1 November 2022. Studies that described strategies to address the psychological impacts experienced by those responding to a public health emergency (i.e., a pandemic, epidemic, natural disaster, or mass casualty event) were eligible for inclusion. No limitations were placed based on study design, language, publication status, or publication date. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Joanna Briggs Institute critical appraisal tools. Discrepancies were resolved through discussion and a third reviewer when needed. Results were synthesized narratively due to the heterogeneity of populations and interventions. Outcomes were displayed graphically using harvest plots. A total of 20,018 records were screened, with 36 unique studies included in the review, 15 randomized controlled trials, and 21 quasi-experimental studies. Results indicate that psychotherapy, psychoeducation, and mind-body interventions may reduce symptoms of anxiety, burnout, depression, and Post Traumatic Stress Disorder, with the lowest risk of bias found among psychotherapy interventions. Psychoeducation appears most promising to increase resilience, with mind-body interventions having the most substantial evidence for increases in quality of life. Few organizational interventions were identified, with highly heterogeneous components. Promoting healthcare workers' mental health is essential at an individual and health system level. This review identifies several promising practices that could be used to support healthcare workers at risk of adverse mental health outcomes as they respond to future public health emergencies.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=203810, identifier #CRD42020203810 (PROSPERO).


Prenatal exposure to persistent organic pollutants and child overweight/obesity at 5-year follow-up: a prospective cohort study.
Prenatal exposure to persistent organic pollutants (POPs), may influence offspring weight gain. More prospective epidemiological studies are needed to compliment the growing body of evidence from animal studies. Serum from 412 pregnant Norwegian and Swedish women participating in a Scandinavian prospective cohort study were collected in 1986-88, and analyses of two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) were conducted. We used linear and logistic regression models with 95% confidence intervals (CIs) to evaluate the associations between maternal serum POP concentrations at 17-20 weeks of gestation and child overweight/obesity (body mass index (BMI) ≥ 85th percentile) at 5-year follow-up. Results were further stratified by country after testing for effect modification. We also assessed potential non-monotonic dose-response (NMDR) relationships. In adjusted linear models, we observed increased BMI-for-age-and-sex z-score (β = 0.18, 95% CI: 0.01-0.35), and increased triceps skinfold z-score (β = 0.15, 95% CI: 0.02-0.27) in children at 5-year follow-up per ln-unit increase in maternal serum perfluorooctane sulfonate (PFOS) concentrations. We observed increased odds for child overweight/obesity (BMI ≥ 85th percentile) for each ln-unit increase in maternal serum PFOS levels (adjusted OR: 2.04, 95% CI: 1.11-3.74), with stronger odds among Norwegian children (OR: 2.96, 95% CI: 1.42-6.15). We found similar associations between maternal serum perfluorooctanoate (PFOA) concentrations and child overweight/obesity. We found indications of NMDR relationships between PFOS and polychlorinated biphenyl (PCB) 153 and child overweight/obesity among Swedish children. We found positive associations between maternal serum PFAS concentrations and child overweight/obesity at 5-year follow-up, particularly among Norwegian participants. We observed some evidence for NMDR relationships among Swedish participants.


Metagenomic signatures of 86 microbial and viral metagenomes.
Previous studies have shown that dinucleotide abundances capture the majority of variation in genome signatures and are useful for quantifying lateral gene transfer and building molecular phylogenies. Metagenomes contain a mixture of individual genomes, and might be expected to lack compositional signatures. In many metagenomic data sets the majority of sequences have no significant similarities to known sequences and are effectively excluded from subsequent analyses. To circumvent this limitation, di-, tri- and tetranucleotide abundances of 86 microbial and viral metagenomes consisting of short pyrosequencing reads were analysed to provide a method which includes all sequences that can be used in combination with other analysis to increase our knowledge about microbial and viral communities. Both principal component analysis and hierarchical clustering showed definitive groupings of metagenomes drawn from similar environments. Together these analyses showed that dinucleotide composition, as opposed to tri- and tetranucleotides, defines a metagenomic signature which can explain up to 80% of the variance between biomes, which is comparable to that obtained by functional genomics. Metagenomes with anomalous content were also identified using dinucleotide abundances. Subsequent analyses determined that these metagenomes were contaminated with exogenous DNA, suggesting that this approach is a useful metric for quality control. The predictive strength of the dinucleotide composition also opens the possibility of assigning ecological classifications to unknown fragments. Environmental selection may be responsible for this dinucleotide signature through direct selection of specific compositional signals; however, simulations suggest that the environment may select indirectly by promoting the increased abundance of a few dominant taxa.


Bioactive recombinant human oncostatin M for NMR-based screening in drug discovery.
Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 μM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening.


Expression of a TNF inhibitor in transgenic mice.
We previously reported that a chimeric protein consisting of the human p55 TNF receptor covalently linked to a murine IgG1 Fc heavy chain acts as an efficient TNF inhibitor, as a result of its high binding affinity for native TNF trimers of both murine and human origin. A transgenic mouse line constitutively expressing the inhibitor from a cytomegalovirus promoter was established. All organs examined expressed the transgene. TNF inhibitory activity was easily detected in plasma of transgenic animals but not in plasma of nontransgenic littermates. This founder line was not found to have any obvious phenotype. Specifically, transgenic mice born to wild-type or transgenic females were indistinguishable from nontransgenic littermates with respect to their size at birth, at three months and at six months of age, with respect to the size and morphology of their lymphoid organs and with respect to their hematocrit, white blood cell count, and differential. Although TNF is known to be constitutively expressed by cells of the thymus and trophoblast, the lack of a clear phenotype in association with the constitutive expression of a TNF inhibitor suggests that TNF may be dispensable in early development.


Ruminal protozoal contribution to the duodenal flow of fatty acids following feeding of steers on forages differing in chloroplast content.
Ruminant products are criticised for their SFA content relative to PUFA, although n-6:n-3 PUFA is desirable for human health ( < 4). Rumen protozoa are rich in unsaturated fatty acids due to engulfment of PUFA-rich chloroplasts. Increasing the chloroplast content of rumen protozoa offers a potentially novel approach to enhance PUFA flow to the duodenum and subsequent incorporation into meat and milk. We evaluated protozoal contribution to duodenal n-3 PUFA flow due to intracellular chloroplast content. A total of six Holstein × Friesian steers were fed, in a two-period changeover design, either straw:concentrate (S:C, 60:40; DM basis; S:C, low chloroplast) or fresh perennial ryegrass (PRG; high chloroplast). Following 12 d adaptation to diet, ruminal protozoal and whole duodenal samples were obtained. N and fatty acid content of whole duodenum and rumen protozoal samples were assessed and protozoal 18S rDNA quantitative PCR performed, enabling calculation of protozoal N flow. The ratio of individual fatty acids:N in rumen protozoal samples was calculated to obtain protozoal fatty acid flows. Based on total fatty acid flow, contribution (%) of protozoa to individual fatty acid flows was calculated. Protozoal fatty acid data and microscopical observations revealed that protozoa were enriched with 18 : 3n-3 following PRG feeding, compared with the S:C diet, due to increased intracellular chloroplast content. However, duodenal protozoal 18S rDNA concentration post PRG feeding was low, indicating rumen retention of the protozoa. Nutrition influences the 18 : 3n-3 content of protozoa; the challenge is to increase protozoal flow to the small intestine, while maintaining sustainable rumen densities.


[Facial hemiatrophy, homolateral cervical linear scleroderma and thyroid disease].
A case of facial hemiatrophy and homolateral cervical band of scleroderma, complicated by hypothyroidism is reported. This case raises two problems: one is the problem of distinction between Romberg's disease and facial hemiatrophy due to a genuine localized scleroderma; the other concerns the relationship between localized scleroderma and dysthyroidism. The generalized scleroderma-dysthyroidism association has now been recognized, but the coexistence of thyroid disease and localized scleroderma has not yet been reported. Several pathogenetic hypotheses on this association are discussed.


[The Inventory "State-Trait Operation Anxiety" (STOA): construction and empirical findings].
This article reports on the construction and empirical evaluation of an instrument for the measurement of surgery-related state and trait anxiety. The inventory "State-Trait Operation Anxiety" (STOA) separately assesses surgery-related anxiety as a comparatively stable personality trait as well as the cognitive and affective components of state anxiety. Results of explorative and confirmatory factor analyses corroborated the unifactorial structure of trait anxiety and the two-factorial structure of state anxiety. Internal consistencies of all scales were highly satisfactory (Cronbach's alpha around 0.90). External relationships of the STOA with trait anxiety, dispositional and actual coping, observed anxiety, as well as indicators of perioperative adjustment confirmed the inventory's validity. An analysis of the scores of the two state anxiety components across the perioperative period demonstrated that these scales are sensitive indicators of state anxiety changes.


Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer's mice and patients.
Neuronal loss is the best neuropathological substrate that correlates with cortical atrophy and dementia in Alzheimer's disease (AD). Defective GABAergic neuronal functions may lead to cortical network hyperactivity and aberrant neuronal oscillations and in consequence, generate a detrimental alteration in memory processes. In this study, using immunohistochemical and stereological approaches, we report that the two major and non-overlapping groups of inhibitory interneurons (SOM-cells and PV-cells) displayed distinct vulnerability in the perirhinal cortex of APP/PS1 mice and AD patients. SOM-positive neurons were notably sensitive and exhibited a dramatic decrease in the perirhinal cortex of 6-month-old transgenic mice (57% and 61% in areas 36 and 35, respectively) and, most importantly, in AD patients (91% in Braak V-VI cases). In addition, this interneuron degenerative process seems to occur in parallel, and closely related, with the progression of the amyloid pathology. However, the population expressing PV was unaffected in APP/PS1 mice while in AD brains suffered a pronounced and significant loss (69%). As a key component of cortico-hippocampal networks, the perirhinal cortex plays an important role in memory processes, especially in familiarity-based memory recognition. Therefore, disrupted functional connectivity of this cortical region, as a result of the early SOM and PV neurodegeneration, might contribute to the altered brain rhythms and cognitive failures observed in the initial clinical phase of AD patients. Finally, these findings highlight the failure of amyloidogenic AD models to fully recapitulate the selective neuronal degeneration occurring in humans.


Association of risk factors with unfavorable outcomes after resection of adult benign intradural spine tumors and the effect of hospital volume on outcomes: an analysis of 18, 297 patients across 774 US hospitals using the National Inpatient Sample (2002-2011).
OBJECT Because of the limited data available regarding the associations between risk factors and the effect of hospital case volume on outcomes after resection of intradural spine tumors, the authors attempted to identify these associations by using a large population-based database. METHODS Using the National Inpatient Sample database, the authors performed a retrospective cohort study that involved patients who underwent surgery for an intradural spinal tumor between 2002 and 2011. Using national estimates, they identified associations of patient demographics, medical comorbidities, and hospital characteristics with inpatient postoperative outcomes. In addition, the effect of hospital volume on unfavorable outcomes was investigated. Hospitals that performed fewer than 14 resections in adult patients with an intradural spine tumor between 2002 and 2011 were labeled as low-volume centers, whereas those that performed 14 or more operations in that period were classified as high-volume centers (HVCs). These cutoffs were based on the median number of resections performed by hospitals registered in the National Inpatient Sample during the study period. RESULTS Overall, 18,297 patients across 774 hospitals in the United States underwent surgery for an intradural spine tumor. The mean age of the cohort was 56.53 ± 16.28 years, and 63% were female. The inpatient postoperative risks included mortality (0.3%), discharge to rehabilitation (28.8%), prolonged length of stay (> 75th percentile) (20.0%), high-end hospital charges (> 75th percentile) (24.9%), wound complications (1.2%), cardiac complications (0.6%), deep vein thrombosis (1.4%), pulmonary embolism (2.1%), and neurological complications, including durai tears (2.4%). Undergoing surgery at an HVC was significantly associated with a decreased chance of inpatient mortality (OR 0.39; 95% CI 0.16-0.98), unfavorable discharge (OR 0.86; 95% CI 0.76-0.98), prolonged length of stay (OR 0.69; 95% CI 0.62-0.77), high-end hospital charges (OR 0.67; 95% CI 0.60-0.74), neurological complications (OR 0.34; 95% CI 0.26-0.44), deep vein thrombosis (OR 0.65; 95% CI 0.45-0.94), wound complications (OR 0.59; 95% CI 0.41-0.86), and gastrointestinal complications (OR 0.65; 95% CI 0.46-0.92). CONCLUSIONS The results of this study provide individualized estimates of the risks of postoperative complications based on patient demographics and comorbidities and hospital characteristics and shows a decreased risk for most unfavorable outcomes for those who underwent surgery at an HVC. These findings could be used as a tool for risk stratification, directing presurgical evaluation, assisting with surgical decision making, and strengthening referral systems for complex cases.


Effects of temperature and humidity on the spread of COVID-19: A systematic review.
Faced with the global pandemic of COVID-19, declared by World Health Organization (WHO) on March 11th 2020, and the need to better understand the seasonal behavior of the virus, our team conducted this systematic review to describe current knowledge about the emergence and replicability of the virus and its connection with different weather factors such as temperature and relative humidity. The review was registered with the PROSPERO database. The electronic databases PubMed, Scopus, Web of Science, Cochrane Library, LILACS, OpenGrey and Google Scholar were examined with the searches restricted to the years 2019 and 2020. Risk of bias assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist tool. The GRADE tool was used to assess the certainty of the evidence. The initial screening identified 517 articles. After examination of the full texts, seventeen studies met the review's eligibility criteria. Great homogeneity was observed in the findings regarding the effect of temperature and humidity on the seasonal viability and transmissibility of COVID-19. Cold and dry conditions were potentiating factors on the spread of the virus. After quality assessment, two studies had a high risk of bias, eleven studies were scored as moderate risk of bias, and four studies were classified as low risk of bias. The certainty of evidence was graded as low for both outcomes evaluated. Considering the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. However, these variables alone could not explain most of the variability in disease transmission. Therefore, the countries most affected by the disease should focus on health policies, even with climates less favorable to the virus. Although the certainty of the evidence generated was classified as low, there was homogeneity between the results reported by the included studies.


Piezo2 channel-Merkel cell signaling modulates the conversion of touch to itch.
The somatosensory system relays many signals ranging from light touch to pain and itch. Touch is critical to spatial awareness and communication. However, in disease states, innocuous mechanical stimuli can provoke pathologic sensations such as mechanical itch (alloknesis). The molecular and cellular mechanisms that govern this conversion remain unknown. We found that in mice, alloknesis in aging and dry skin is associated with a loss of Merkel cells, the touch receptors in the skin. Targeted genetic deletion of Merkel cells and associated mechanosensitive Piezo2 channels in the skin was sufficient to produce alloknesis. Chemogenetic activation of Merkel cells protected against alloknesis in dry skin. This study reveals a previously unknown function of the cutaneous touch receptors and may provide insight into the development of alloknesis.