SARS-CoV-2 transmission dynamics in the urban-rural interface.

OBJECTIVES: 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. STUDY DESIGN: This was a population modeling study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Feasibility of changing for a rechargeable constant current neurostimulator in Parkinson's disease.

BACKGROUND: 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). OBJECTIVE: To determine the feasibility and safety of replacing a CV-nrIPG by a CC-rIPG in Parkinson's disease (PD) and the subsequent outcome. METHODS: 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. RESULTS: 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. CONCLUSIONS: Replacing CV-nrIPG by CC-rIPG is safe and well tolerated but require neurological expertise to set the new parameters of stimulation.

Bovine semen thermoresistance tests and their correlation with pregnancy rates after fixed-time artificial insemination / Testes de termorresistência do sêmen bovino e sua correlação com taxas de prenhez após inseminação artificial em tempo fixo

The objective of the study was to determine whether or not there is a correlation between thermoresistance tests (TT) after semen thawing and pregnancy rate (PR) after fixed-time artificial insemination (FTAI). Four different TT were performed on ten samples used for AI; a rapid test (RTT) (30min / 46°C) and three slow tests (STT): STT1 (60min/38°C), STT2 (180min/38°C), and STT3 (300min/38°C). Two hundred and fifteen multiparous crossbred cows were submitted to FTAI under the following protocol: on day zero (d0) the animals received a P4 device +EB; on d7 PGF2α; on d8 P4 was removed and eCG+EC were administered; IATF was performed on d10. Three gestational diagnoses (G D) were performed on d40, d70 and d120. The mean sperm motility (%) in RTT and STTs were 19.84±6.13, 28.55±10.48, 17.62±5.87 and 8.63±3.46, respectively, and TP in the three DG 61.86%, 57.67%, and 55.81%, respectively. Through Person test a significant negative correlation (P< 0.05) was found between STT2 and PR at 60 days (r= -0.644) and between STT3 and all TPs (r= -0.774, -0.752, 0.748). It was concluded that TT parameters are not able to determine correlation between semen quality and TP.(AU)

O objetivo do presente estudo foi determinar se há ou não correlação entre testes de termorresistência (TT) após descongelamento do sêmen e taxa de prenhez (TP) após inseminação artificial em tempo fixo (IATF). Quatro diferentes TT foram realizados nas 10 amostras utilizadas para a IA; um teste rápido (RTT) (30min/46°C) e três testes lentos (STT): STT1 (60min/38°C), STT2 (180min/38°C) e STT3 (300min/38°C). Duzentas e quinze vacas cruzadas multíparas foram submetidas à IATF sob o seguinte protocolo: no dia zero (d0), os animais receberam um dispositivo de P4+EB; em d7, PGF2α; em d8, retirou-se P4 e eCG+EC administrados; no d10, foi realizada IATF. Três diagnósticos gestacionais (DG) foram feitos, em d40, d70 e d120. As médias de motilidade espermática (%) em RTT e STTs foram 19,84±6,13, 28,55±10,48, 17,62±5,87 e 8,63±3,46, respectivamente, e TP nos três DG 61,86%, 57,67% e 55,81%, respectivamente. Por meio do teste de Person, uma correlação negativa significativa (P<0,05) foi encontrada entre os resultados de STT2 e PR aos 60 dias (r=-0,644) e entre STT3 e todas TPs (r=-0,774, -0,752 e -0,748). Concluiu-se que parâmetros de TT não são capazes de determinar correlação entre qualidade do sêmen e TP.(AU)

Optimizing the deep brain stimulation care pathway in patients with Parkinson's disease.

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.

The Utility of CSF for the Diagnosis of Primary and Secondary Monoamine Neurotransmitter Deficiencies.

Biogenic amine defects constitute a complex and expanding group of neurotransmitter disorders affecting cognitive, motor and autonomic system development, mostly in the pediatric age. In recent years different enzymatic defects have been identified impairing the tetrahydrobiopterin cofactor pathway and/or biogenic amine synthesis, catabolism and transport, with subsequent new disease entities described. The lumbar puncture, with subsequent withdrawal of cerebrospinal fluid (CSF), remains a key step in the diagnostic procedure. Due to the specific nature of CSF, timing of analysis, sample collection and storage, technical issues of the analytic process are still crucial for the diagnosis and follow-up of patients. A progressive approach to the diagnosis of biogenic amine defects is presented, pointing out criticalities and difficulties concerning sample collection and results interpretation, especially due to the increasing reports of secondary neurotransmitter alterations that, at present, constitute a challenge.

Clinical, biochemical and molecular characterization of prosaposin deficiency.

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.

Niemann-Pick Type C-2 Disease: Identification by Analysis of Plasma Cholestane-3ß,5α,6ß-Triol and Further Insight into the Clinical Phenotype.

INTRODUCTION: Niemann-Pick type C disease is a rare disorder caused by impaired intracellular lipid transport due to mutations in either the NPC1 or the NPC2 gene. Ninety-five % of NPC patients show mutations in the NPC1 gene. A much smaller number of patients suffer from NPC2 disease and present respiratory failure as one of the most frequent symptoms. Several plasma oxysterols are highly elevated in NPC1 and can be used as a biomarker in the diagnosis of NPC1. METHODS: Plasma cholestane-3ß,5α,6ß-triol was evaluated as biomarker for NPC2 by GC/MS and LC-MS/MS analysis. The diagnosis was confirmed by Sanger sequencing and filipin staining. RESULTS: We report three NPC2 patients with typical respiratory problems and a detailed description of the nature of the lung disease in one of them. All patients had elevated levels of plasma cholestane-3ß,5α,6ß-triol. In two of these patients, the positive oxysterol result led to a rapid diagnosis of NPC2 by genetic analysis. The phenotype of the third patient has been described previously. In this patient a cholestane-3ß,5α,6ß-triol concentration markedly above the reference range was found. CONCLUSIONS: Measurement of plasma cholestane-3ß,5α,6ß-triol enables to discriminate between controls and NPC1 and NPC2 patients, making it a valuable biomarker for the rapid diagnosis not only for NPC1 but also for NPC2 disease.The measurement of oxysterols should be well kept in mind in the differential diagnosis of lysosomal diseases, as the elevation of oxysterols in plasma may speed up the diagnosis of NPC1 and NPC2.

[Partial versus radical nephrectomy for renal cell carcinoma involving peri renal fat. Oncological and functional outcomes]. / Néphrectomie partielle versus élargie en cas d'envahissement de la graisse périrénale. Résultats oncologiques et fonctionnels.

PURPOSE: In the latest guidelines of the European Association of Urology, partial nephrectomy was a reference standard in tumors less than 7cm confined to the kidney. The invasion of the perirenal fat and therefore dissection in a potentially tumor tissue with an increased risk of recurrence. MATERIAL: From 1995 to 2009, we retrospectively evaluated the oncological outcomes of partial versus radical nephrectomy in tumors with local extension beyond the boundaries of the kidney, without adrenal involvement or metastatic lymph node extension. We evaluated the histological factors influencing the prognostic. RESULTS: A total of 43patients have been included (ten partial and 33radical nephrectomy). We did not found any significant difference in terms of specific and recurrence-free survival between partial and radical nephrectomy in tumor invading the perirenal fat (P=0.739 and P=0.683 respectively). Factors influencing the prognosis were the Fuhrman grade (P=0.010), the invasion of the urinary tract (P=0.017) and the presence of a positive surgical margin (P=0.041). The renal function was better after partial nephrectomy. The complication rate was similar between partial and radical nephrectomy. CONCLUSION: The perirenal fat invasion by kidney tumor did not impact the oncological outcomes of partial versus radical nephrectomy with better functional outcomes for partial nephrectomy.

[Intraoperative monitoring of brainstem auditory evoked potentials during microvascular decompression of cranial nerves in cerebellopontine angle]. / Monitorage peropératoire des potentiels évoqués auditifs précoces dans la chirurgie de décompression microchirurgicale des nerfs crâniens de l'angle pontocérébelleux.

Brainstem auditory evoked potentials (BAEP) monitoring is a useful tool to decrease the danger of hearing loss during pontocerebellar angle surgery, particularly in microvascular decompression (MVD). Critical complications arising during MVD surgery are the stretching of the VIII nerve - the main cause of hearing loss - labyrinthine artery manipulation, direct trauma with instruments, or a nearby coagulation, and at end of the surgery neocompression of the cochlear nerve by the prosthesis positioned between the conflicting vessel(s) and the VIIth-VIIIth nerve complex. All these dangers warrant the use of BEAP monitoring during the surgical team's training period. Based on delay in latency of peak V, we established warning thresholds that can provide useful feedback to the surgeon to modify the surgical strategy: the initial signal at 0.4 ms is considered the safety limit. A second signal threshold at 0.6 ms (warning signal for risk) corresponds to the group of patients without resultant hearing loss. The third threshold characterized by the delay of peak V is at 1 ms (warning signal for a potentially critical situation). BAEP monitoring provides the surgeon with information on the functional state of the auditory pathways and should help avoid or correct manoeuvres that can harm hearing function. BAEP monitoring during VIIth-VIIIth complex surgery, particularly in MVD of facial nerves for HFS is very useful during the learning period.

Subthalamic nucleus stimulation in Parkinson's disease : anatomical and electrophysiological localization of active contacts.

OBJECTIVES: 1 - To assess the anatomical localization of the active contacts of deep brain stimulation targeted to the subthalamic nucleus (STN) in Parkinson's disease patients. 2 - To analyze the stereotactic spatial distribution of the active contacts in relation to the dorsal and the ventral electrophysiologically-defined borders of the STN and the stereotactic theoretical target. METHODS: Twenty-eight patients underwent bilateral high-frequency stimulation of the STN (HFS-STN). An indirect anatomical method based on ventriculography coupled to electrophysiological techniques were used to localize the STN. Clinical improvement was evaluated by Unified Parkinson's Disease Rating Scale motor score (UPDRS III). The normalized stereotactic coordinates of the active contact centres, dorsal and ventral electrophysiologically-defined borders of the STN were obtained from intraoperative X-rays images. These coordinates were represented in a three-dimensional stereotactic space and in the digitalized atlas of the human basal ganglia. RESULTS: HFS-STN resulted in significant improvement of motor function (62.8%) in off-medication state and levodopa-equivalent dose reduction of 68.7% (p < 0.05). Most of the active contacts (78.6%) were situated close to (+/- 1.6 mm) the dorsal border of the STN (STN-DB), while 16% were dorsal and 5.4% were ventral to it. Similar distribution was observed in the atlas. The euclidean distance between the STN-DB distribution center and the active contacts distribution center was 0.31 mm, while the distance between the active contacts distribution center and the stereotactic theoretical target was 2.15 mm. Most of the space defined by the active contacts distribution (53%) was inside that defined by the STN-DB distribution. CONCLUSION: In our series, most of the active electrodes were situated near the STN-DB. This suggests that HFS-STN could influence not only STN but also the dorsal adjacent structures (zona incerta and/or Fields of Forel).

[Microsurgical vascular decompression for hemifacial spasm. Follow-up over one year, clinical results and prognostic factors. Study of a series of 100 cases]. / Décompression vasculaire microchirurgicale pour spasme hémifacial. Résultats cliniques à plus d'un an et facteurs pronostiques. Etudes d'une série de 100 cas.

BACKGROUND AND PURPOSE: The results of a series of 100 patients operated on for hemifacial spasm (HFS), using microsurgical vascular decompression (MVD), are reported. METHOD: MVD was performed through a retromastoid keyhole approach, under monitoring of brainstem auditory evoked potentials (BAEP) and facial EMG, and consisted in dissection of VII nerve from conflicting vessel(s), and interposition of Teflon fibers and/or screen(s). RESULTS: The offending vessels found were: the antero-inferior cerebellar artery in 57 cases, the postero-inferior cerebellar artery in 56 cases, the vertebrobasilar artery in 22 cases. A multiple conflict was found in 32 cases (32%). The result was considered excellent if there was no residual spasm, good if only "minimal twitching" remained with relief>80%, poor for spasm relief 20 to 80%, and as a failure if relief<20%. The effect of MVD was satisfying (excellent or good) in 75 patients (75%) at discharge (10th day) and in 85 (85%) after 1 to 18 years follow-up (mean: 5 years). Amongst the latter patients, 29 (34%) experienced a delayed (up to 3(1/2) years in one) cure. Spasm recurrence was noted in 9 cases after satisfying effect on discharge. We encountered following permanent neurological complications: 1 facial palsy, 7 cases of hearing deficit (5 of them complete), and 1 case of IX-X deficit. Neither death nor ischaemic complication at brainstem or cerebellum. Most of our hearing complications occurred before using intraoperative BAEP monitoring (3 cases of cophosis among our first 7 patients vs 2 out of our last 93). Local complications were: 1 meningitis, 8 cases of CSF leakage requiring either a series of lumbar punctures or a lumbar external drain, and 3 cases of wound infection and/or delayed woundhealing requiring surgical treatment. CONCLUSIONS: Our data are consistent with those of the literature, especially concerning high rate of long-term success and low complication rate of MVD for HFS. We do not recommend early re-operation in case of initial poor result. Again, the necessity of intraoperative BAEP monitoring to prevent hearing morbidity is highlighted.

[Evidence of cerebral involvement in the chronic stage of Chagas disease obtained using the P300 potential and quantified electroencephalography]. / Evidencias de compromiso cerebral en el estadio crónico de la enfermedad de Chagas obtenidas por medio del potencial P300 y de electroencefalografía cuantificada.

It is already known the involvement of the peripheral nervous system in chronic stages of Chagas disease. Tomographic and neuropsychological evidence of brain compromise has been included recently. In order to evaluate the neurophysiological counterpart of cerebral involvement, we studied P300 evoked potential and quantified EEG (qEEG) of 35 patients (26-55 years), and compared to an equal number of control subjects (29-55 years). We have found increased P300 latency compared to the control group (331.24 +/- 24. 02 vs 318.86 +/- 23.18) (p=0.01716). qEEG showed lower relative Beta 1 power in the patients group (p=1.6E5), and the principal frequency 1 Hz slower in the same group (p=0.01077). Multivariate analysis showed three subpopulations: a normal one, pathological one with higher Alpha power and pathological with Alpha decrement and DeltaTheta increment. Pathological findings represented 20% for the qEEG and 11.43% for cognitive potentials. Cardiac and neurologic involvement were not correlated. We conclude that there is clear electrophysiological evidence of cerebral involvement in chronic Chagas disease, thus reinforcing findings obtained by other methods.

Double versus single renal allografts from aged donors.

BACKGROUND: The age limit of the cadaver kidney donors is increasing in response to the growing demand for renal transplantation. Simultaneous double kidney transplantation (SDKT) with kidneys obtained from elderly adults has been proposed to increase the transplantation number and improve its results. However, if SDKT is performed when there are no clear indications, a negative effect could be produced on the total number of transplanted patients as both kidneys would be used for only one recipient. MATERIAL AND METHODS: In December 1996 we designed a transplantation protocol to be able to extend the selection of cadaver kidney donors with normal serum creatinine levels without establishing any age limit. A pregraft renal biopsy was always performed to analyze the glomerulosclerosis (GE) percentage whenever the donors were 60 years of age or older. A SDKT was performed in a single recipient when the donor age was 75 years or older or when the donors between 60 and 74 years old had a GE rate of more than 15%. On the contrary, a single kidney transplantation was performed in two different recipients for kidneys from donors between 60 and 74 years of age with a GE rate of less than 15%. Kidneys having GE rates of more than 50% were discarded for transplantation. Donor kidneys from subjects younger than 60 years of age were always used for a single kidney transplantation. RESULTS: Based on the above mentioned protocol, from December 1996 to May 1998, 181 patients received a kidney transplantation in our hospital. These patients were divided into three groups: group I which included the SDKT recipients (n=21), group II or single kidney recipients from 60- to 74-year-old donors (n=40), and group III or recipients from <60-year-old donors (n=120). The mean follow-up time was 15+/-5 months (range 6-24). Mean donor age was 75+/-7 years in group I, this was significantly higher than in group II (67+/-4, P<0.001) and group III (37+/-15, P<0.001). The primary nonfunction rate was low in the three groups, there being no statistically significant differences (5, 5, and 4%, respectively). A significantly greater percentage of patients from group I (76%) presented immediate renal graft function as compared with group II (43%, P<0.01) and III (50%, P<0.05). The acute rejections rate was very low in all three groups (9.5, 7.5, and 22%, respectively) with significant differences between groups II and III (P<0.05). No significant differences between the different groups were observed for one year actuarial patient survival (100, 95, and 98%, respectively) or graft survival rates (95, 90, and 93%, respectively). The 6-month serum creatinine levels were excellent in the three groups, although there were significant differences between groups I and II (1.6+/-0.3 vs. 1.9+/-0.6 mg/dl, P<0.05), II and III (1.9+/-0.6 vs. 1.4+/-0.4 mg/dl, P<0.001), and I and III (P<0.05). CONCLUSIONS: Simultaneous double kidney transplantations make it possible to use kidneys from extremely elderly donors (>75 years) or those whose GE>15%. In addition, kidneys from donor 60-74 years old in which the GE<15% can be used for single kidney transplantations in two different recipients with excellent results.