The ontogenetic origins of the bacteriocytes, which are cells that harbour bacterial intracellular endosymbionts in multicellular animals, are unknown. During embryonic development, a series of ...morphological and transcriptional changes determine the fate of distinct cell types. The ontogeny of bacteriocytes is intimately linked with the evolutionary transition of endosymbionts from an extracellular to an intracellular environment, which in turn is linked to the diet of the host insect. Here we review the evolution and development of bacteriocytes in insects. We first classify the endosymbiotic occupants of bacteriocytes, highlighting the complex challenges they pose to the host. Then, we recall the historical account of the discovery of bacteriocytes. We then summarize the molecular interactions between the endosymbiont and the host. In addition, we illustrate the genetic contexts in which the bacteriocytes develop, with examples of the genetic changes in the hosts and endosymbionts, during specific endosymbiotic associations. We finally address the evolutionary origin as well as the putative ontogenetic or developmental source of bacteriocytes in insects.
Apathy has been reported to occur after subthalamic nucleus stimulation, a treatment of motor complications in advanced Parkinson’s disease. We carried out a prospective study of the occurrence of ...apathy and associated symptoms, predictors and mechanisms in the year following subthalamic stimulation. Dopamine agonist drugs were discontinued immediately after surgery and levodopa was markedly reduced within 2 weeks. Apathy and depression were assessed monthly, using the Starkstein apathy scale and the Beck Depression Inventory. Dopamine agonists were re-introduced if patients developed apathy or depression. Preoperative non-motor fluctuations were evaluated using the Ardouin Scale. Depression, apathy and anxiety were evaluated both on and off levodopa. Analysis of predictors of apathy was performed using a Cox proportional hazard model. Twelve patients who developed apathy and a control group of 13 patients who did not underwent 11C-raclopride positron emission tomography scanning before and after oral intake of methylphenidate. In 63 patients with Parkinson’s disease treated with subthalamic stimulation, dopaminergic treatment was decreased by 82% after surgery. Apathy occurred after a mean of 4.7 (3.3–8.2) months in 34 patients and was reversible in half of these by the 12-month follow-up. Seventeen patients developed transient depression after 5.7 (4.7–9.3) months and these fell into the apathy group with one single exception. At baseline, fluctuations in depression, apathy and anxiety scores were greater in the group with apathy. Fluctuations in apathy, depression and anxiety ratings during a baseline levodopa challenge were also significant predictors of postoperative apathy in univariate analysis, but not motor and cognitive states or the level of reduction of dopaminergic medication. The multivariate model identified non-motor fluctuations in everyday life and anxiety score during the baseline levodopa challenge as two independent significant predictors of postoperative apathy. Without methylphenidate, 11C-raclopride binding potential values were greater in apathetic patients bilaterally in the orbitofrontal, dorsolateral prefrontal, posterior cingulate and temporal cortices, left striatum and right amygdala, reflecting greater dopamine D2/D3 receptor density and/or reduced synaptic dopamine level in these areas. The variations of 11C-raclopride binding potential values induced by methylphenidate were greater in non-apathetic patients in the left orbitofrontal cortex, dorsolateral prefrontal cortex, thalamus and internal globus pallidus and bilaterally in the anterior and posterior cingulate cortices, consistent with a more important capacity to release dopamine. Non-motor fluctuations are related to mesolimbic dopaminergic denervation. Apathy, depression and anxiety can occur after surgery as a delayed dopamine withdrawal syndrome. A varying extent of mesolimbic dopaminergic denervation and differences in dopaminergic treatment largely determine mood, anxiety and motivation in patients with Parkinson’s disease, contributing to different non-motor phenotypes.
Prosaposin (PSAP) deficiency is an ultra‐rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with seven subjects reported so far. Here, we provide the ...clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC‐MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC‐MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (LysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement.
The seventh edition of the AASHTO LRFD Bridge Design Specifications (2016 interim) includes revised provisions for the design of deep beams using the strut-and-tie method. The validity and accuracy ...of these provisions as applied to simply supported deep beams loaded in a manner that generates an inflection point between the supports was investigated in this research. As part of a course-related laboratory investigation, graduate students at the University of Texas at Austin used these provisions to design two reduced-scale deep beams. The specimens were subsequently constructed and tested. The experimental behaviors of the specimens including governing failure modes, load-displacement curves, and their ultimate capacities were investigated and compared with estimates developed from the strut-and-tie method. The results obtained validated the suitability of the revised provisions for the design of deep beams with inflection points located between supports. Additionally, the students developed pre-test estimates for the behaviors and strengths of the two deep beam specimens using the finite element software program VecTor2. While there was some variation among the computed responses, the blind predictions accurately captured governing failure modes and provided reasonable capacity estimates. Keywords: deep beam; finite element analysis of reinforced concrete; strut-and-tie.
As the world responds to the coronavirus outbreak, the role of public health in ensuring equitable health care that considers the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics ...in rural communities is still a challenge. The same suppression and mitigation measures have been implemented homogeneously, ignoring the differences between urban and rural areas. We propose an epidemiological model and simulate the dynamics of SARS-CoV-2 in urban and rural areas considering the interaction between these regions.
This was a population modeling study.
A compartmental epidemiological model was formulated to simulate the transmission of SARS-CoV-2 in urban and rural areas. We use the model to investigate the impact of control strategies focused on the urban-rural interface to contain the epidemic size of SARS-CoV-2 in rural areas.
Considering five different levels for the exposition rate in urban areas and keeping intrarural and urban-rural exposition rates fixed, the preventive measures reduce the size and delay the peak for the urban infectives. The response of infected individuals and cumulative deaths in rural areas upon changes in the urban dynamics was small but not negligible. On the other hand, preventive measures focused on the urban-rural interface impact the number of infected individuals and deaths in rural areas.
The maintenance of SARS-CoV-2 in rural areas depends on the interaction of individuals at the urban-rural interface. Thus, restrictive measures established by the governments would not be required within rural areas. We highlight the importance of focused preventive measures on the urban-rural interface to reduce the exposure and avoid the transmission of SARS-CoV-2 to rural communities.
Objective
To assess the long-term efficacy and safety of bilateral subthalamic nucleus (STN) stimulation in patients with advanced Parkinson’s disease (PD).
Methods
42 consecutive patients with ...idiopathic PD treated with bilateral STN stimulation were enrolled. Parkinsonian status, medication intake and neuropsychological evaluation were assessed preoperatively and at 1 and 5 years postoperatively in on and off medication/on and off stimulation conditions.
Results
23 patients could be followed-up 5 years after surgery. In the remaining cases, 5 died, 1 could not be assessed because of device removal for infection, 1 decided not to be stimulated, and 11 were lost of follow-up (one because of a liver carcinoma and the others because they refused the formal four conditions of assessment). STN stimulation reduced the UPDRS motor score by 55 % compared to baseline in the offmedication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 74 %, 66 %, 59 %, 17 % and 37 %, respectively. UPDRS part II scores were reduced by 38 %. The dopaminergic treatment daily dose was reduced by 54.4 % after surgery. Axial dopa-unresponsive signs worsened in some patients. Among the 42 initial patients we observed the following: 2 brain hemorrhages, 3 infections of the device, 2 phlebitis and 1 pulmonary embolism. In addition, 2 patients needed a repositioning of the electrode. Among the 23 patients followed at 5 years, long lasting side effects consisted in dysarthria (56 %), depression (39 %), eyelid opening apraxia (30.4 %) and apathy (4.3 %).
Conclusions
Our data confirm that bilateral STN stimulation is beneficial in the long-term for PD patients but does not prevent disease progression and the occurence of axial levodopa unresponsive signs in some patients.
Dalbavancin is a lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). The aim of the study was to evaluate the efficacy and safety in all ...patients who received at least one administration of dalbavancin. Methods: We carried out a retrospective study of the use of dalbavancin in 55 patients at the Azienda Ospedaliera Ospedali Riuniti Umberto I (Ancona, Italy) from February 2017 to May 2020 and compared “on label” and “off label” use of dalbavancin in ABSSSI and non-ABSSSI. Results: A total of 55 patients were included in the study. The median age was 61 years; 51% had ABSSSI; 24% had prosthetic joint infections, and 14% had osteomyelitis. A total of 53% received a single 1500 mg infusion of dalbavancin, and 18% received a second dose 14 days later; 24% of patients received further doses at 14-day intervals. In 91% of cases, patients achieved clinical objectives with dalbavancin: 96% of patients with ABSSSI and 69% of those with prosthetic joint infections. Conclusions: Dalbavancin was shown to have an excellent tolerability profile and to be a highly successful therapeutic approach even in those cases treated “off-label”.
Little is known about outcome and settings adaptations after replacement of constant-voltage non-rechargeable implantable pulse generator (CV-nrIPG) by constant-current rechargeable IPG (CC-rIPG).
To ...determine the feasibility and safety of replacing a CV-nrIPG by a CC-rIPG in Parkinson's disease (PD) and the subsequent outcome.
A prospective cohort of thirty PD patients, whose CV-nrIPG was replaced by a CC-rIPG in University Hospital of Lyon between January 2017 and December 2018 (rIPG group) and 39 PD patients, who underwent the replacement of a CV-nrIPG by the same device in 2016 (nrIPG group), were enrolled in this study. Three surgeons performed the operations. Duration of hospitalization for the replacement as well as the number of in or outpatient visits during the first 3 months after the surgery were recorded. In the rIPG group, we compared preoperative DBS settings and the theoretical amplitude estimated using Ohm's law to the amplitude used at the end of follow-up. We assessed patients’ and clinicians’ opinion on the patient global functioning after the replacement using Clinical Global Impression score.
Duration of hospitalization (P=0.47) and need for additional hospitalizations (P=0.73) or consultations (P=0.71) to adapt DBS parameters did not differ between the two groups. Neurological condition (CGI score) was considered as unchanged by both patients and neurologists. Final amplitude of stimulation using CC-rIPG was not predicted by Ohm's law in most cases.
Replacing CV-nrIPG by CC-rIPG is safe and well tolerated but require neurological expertise to set the new parameters of stimulation.
Management of Parkinson’s disease (PD) using deep brain stimulation (DBS) requires complex care in specialized, multidisciplinary centers. A well-organized, efficient patient flow is crucial to ...ensure that eligible patients can quickly access DBS. Delays or inefficiencies in patient care may impact a center’s ability to meet demand, creating a capacity bottleneck. Analysis of the current practices within a center may help identify areas for improvement. After external audit of the DBS workflow of the Lyon Neurological Hospital and comparison with other European centers, manageable steps were suggested to restructure the care pathway. Propositions of the audit comprised, for example: (1) directly admitting referred patients to hospital, without a prior neurological outpatient visit and (2) including the preoperative anesthesia consultation in the hospital stay 1 month before surgery, not separately. This reorganization (between 2013 and 2016) was performed without increases in hospital medical resources or costs. The time from patients’ first referral to surgery was reduced (from 22 to 16 months;
p
= 0.033), as was the number of pre- and postoperative patient visits (11–5;
p
= 0.025) and the total cumulative length of in-hospital stay (20.5–17.5 nights;
p
= 0.02). Ultimately, the total number of PD consultations increased (346–498 per year), as did the number of DBS implants per year (32–45 patients). In this single center experience, restructuring the DBS care pathway allowed a higher number of PD patients to benefit from DBS therapy, with a shorter waiting time and without decreasing the quality of care.
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