Real-Time assessment of organ vitality during the transplantation procedure

Although organ transplantation has become well established as a treatment modality for many patients with organ failure, little attention has been given to the evaluation of organ quality during its various steps. A critical factor in the success of the actual engraftment procedure is the integrity of energy metabolism and oxygen balance (supply/demand) at the microvasculature and intracellular mitochondrial level. The supply of oxygen to the cells is dependent on the saturation of hemoglobin (HbO₂), tissue blood flow, and tissue oxygen partial pressure. The mitochondrial reduced nicotinamide adenine dinucleotide redox state represents oxygen balance in the tissue. Although these parameters can be monitored in all tissues of the body, demand for oxygen may be organ-specific. The various steps surrounding transplantation may require different techniques for the evaluation of tissue vitality. Assessment of blood flow or HbO₂ is not possible during preservation of the organ. On the other hand, because extracellular levels of potassium may represent the energy demand processes in many organs, monitoring of extracellular potassium as an indicator of ionic homeostasis may provide important information regarding the quality of the preservation techniques. Although a large number of relevant studies have been performed in small laboratory animals, real-time monitoring in patients needs more practical tools. We present here the principles of multiparametric monitoring by which tissue vitality may be measured in both experimental and clinical situations. Much of the relevant literature on the subject is limited to the monitoring of kidney and liver. There are also some data on the monitoring of skin flaps. We have reviewed the major published reports in which organ and tissue vitality and quality were assessed in real time and will describe tissue and organ oxygen balance, vitality principles, technologic features of the various monitoring techniques, the clinical or experimental tools available and the conceptual and technologic aspects of the multiparametric monitoring concept. We will also discuss both experimental results and preliminary clinical observations by using multiparametric monitoring.     

National Scale Real-Time Surveillance of SARS-CoV-2 Variants Dynamics by Wastewater Monitoring in Israel

In this report, we describe a national-scale monitoring of the SARS-CoV-2 (SC-2) variant dynamics in Israel, using multiple-time sampling of 13 wastewater treatment plants. We used a combination of inclusive and selective quantitative PCR assays that specifically identify variants A19/A20 or B.1.1.7 and tested each sample for the presence and relative viral RNA load of each variant. We show that between December 2020 and March 2021, a complete shift in the SC-2 variant circulation was observed, where the B.1.1.7 replaced the A19 in all examined test points. We further show that the normalized viral load (NVL) values and the average new cases per week reached a peak in January 2021 and then decreased gradually in almost all test points, in parallel with the progression of the national vaccination campaign, during February–March 2021. This study demonstrates the importance of monitoring SC-2 variant by using a combination of inclusive and selective PCR tests on a national scale through wastewater sampling, which is far more amendable for high-throughput monitoring compared with sequencing. This approach may be useful for real-time dynamics surveillance of current and future variants, such as the Omicron (BA.1, BA.2) and other variants.     

Emergence of genetically linked vaccine-originated poliovirus type 2 in the absence of oral polio vaccine,Jerusalem, April to July 2022

We report an emergence and increase in poliovirus type 2 detection via routine wastewater surveillance in three non-overlapping regions in the Jerusalem region, Israel, between April and July 2022. Sequencing showed genetic linkage among isolates and accumulation of mutations over time, with two isolates defined as vaccine-derived polioviruses (VDPV). This demonstrates the emergence and potential circulation of type 2 VDPV in a high-income country with high vaccine coverage and underscores the importance of routine wastewater surveillance during the polio eradication.     

Results of treatment with topical mitomycin C 0.02% following excision of primary pterygium.

AIMS--The effectiveness of instillation of mitomycin C eyedrops on the recurrence rate of pterygium was assessed in patients undergoing primary pterygium surgery. Any side effects were also noted. METHODS--Primary pterygia in 38 consecutive patients were surgically excised during July to December 1992. After surgery, mitomycin C 0.02% eyedrops twice daily for 5 days as well as dexamethasone 0.1% four times tapered for the next 6 weeks were instilled. Postoperative follow up ranged from 6 to 11 months. RESULTS--In one patient the pterygium recurred after 3 months (recurrence rate 2.6%). The side effects encountered were: avascularised sclera in 13 cases between 1-10 months postoperatively; ocular discomfort and lacrimation in five cases; superficial punctate keratitis during the first month in three cases; pyogenic granuloma in two cases. In one patient steroid induced increased intraocular pressure was found 4 weeks after surgery. The adverse side effects were all mild, self limiting, and easily treated. CONCLUSION--This study suggests that postoperative instillation of mitomycin C 0.02% eyedrops twice daily for 5 days following excision of primary pterygium is an effective and safe treatment to obviate pterygium recurrence.     

Congenital hereditary hypothyroidism--prenatal diagnosis and treatment

Intrauterine diagnosis of congenital hypothyroidism was established on the basis of TSH concentration in amniotic fluid in the 22nd week of gestation for the offspring of a couple both known to have an iodide organification defect. Prenatal treatment consisted of intramniotic injections of 500 mcg Na-1-thyroxine, which was administered from the first amniocentesis until one week before delivery. Following delivery, the diagnosis was confirmed by the elevated level of TSH, 60.5 uU/ml, and a gradual decrease of fT4 to 0.8 ng/ml. Regular substitution therapy was commenced on the third day of life. The normal shape and location of the thyroid gland was demonstrated by Technetium scintiscan. At 18 months the infant revealed no significant deviation from normalcy in growth or mental capacity. This experience indicates that testing of amniotic fluid for TSH in the 22nd week of gestation can be diagnostic for congenital primary hypothyroidism. Furthermore, it is suggested that the treatment approach described is warranted in all cases in which there is a high risk of congenital primary hypothyroidism.     

Attentional states and the degree of visual adaptation to gratings.

We studied top-down attentional effects on adaptation to two aspects of sinusoidal gratings: contrast (CTE: contrast threshold elevation for detection) and orientation (TAE: tilt aftereffect, bias in perceived orientation). Adaptation was examined under five different behavioral conditions designed to assess the effect of alertness, spatial attention and the dimension attended. Alertness increased CTE, but had no effect on TAE. Spatial attention increased TAE, but had no effect on CTE. TAE (but not CTE) was also sensitive to the attended dimension. It was greater when gratings' contrast rather than orientation was attended. The different patterns of top-down effects on CTE compared with TAE are consistent with these two types of adaptation taking place at different levels along the visual hierarchy: CTE occurs at very low-levels, where activity is affected by alertness but not by spatial attention, whereas TAE occurs at subsequent stages, which are modulated by selective attention.     

Embryonic and adult stem cells as a source for cell therapy in Parkinson’s disease

The rationale behind the use of cells as therapeutic modalities for neurodegenerative diseases in general, and in Parkinson’s disease (PD) in particular, is that they will improve patient’s functioning by replacing the damaged cell population. It is reasoned that these cells will survive, grow neurites, establish functional synapses, integrate best and durably with the host tissue mainly in the striatum, renew the impaired wiring, and lead to meaningful clinical improvement. To increase the generation of dopamine, researchers have already transplanted non-neuronal cells, without any genetic manipulation or after introduction of genes such as tyrosine hydroxylase, in animal models of PD. Because these cells were not of neuronal origin, they developed without control, did not integrate well into the brain parenchyma, and their survival rates were low. Clinical experiments using cell transplantation as a therapy for PD have been conducted since the 1980s. Most of these experiments used fetal dopaminergic cells originating in the ventral mesencephalic tissue obtained from fetuses. Although it was shown that the transplanted cells survived and some patients benefited from this treatment, others suffered from severe dyskinesia, probably caused by the graft’s excessive and uncontrolled production and release of dopamine. It is now recognized that cell-replacement strategy will be effective in PD only if the transplanted cells have the same abilities, such as dopamine synthesis and control release, reuptake, and metabolizing dopamine, as the original dopaminergic neurons. Recent studies on embryonic and adult stem cells have demonstrated that cells are able to both self-renew and produce differentiated tissues, including dopaminergic neurons. These new methods offer real hope for tissue replacement in a wide range of diseases, especially PD. In this review we summarize the evidence of dopaminergic neuron generation from embryonic and adult stem cells, and discuss their application for cell therapy in PD.