SARS-COV-2 INFECTION AND INVOLVEMENT OF PERIPHERAL NERVOUS SYSTEM: A CASE SERIES OF CARPAL TUNNEL SYNDROME AGGRAVATION OR NEW ONSET WITH COVID-19 DISEASE AND A REVIEW OF LITERATURE.

COVID-19 may be asymptomatic or have a typical presentation with fever, cough, anosmia, lymphocytopenia. In some cases, it occurs with a "chimeric" presentation, with more subtle and ambiguous symptoms which may be initially misdiagnosed and are referred to in long covid condition. A possible central and peripheral nervous system involvement has been recognized. We present our experience and review the literature about association between carpal tunnel syndrome (CTS) and hand's arthritis presenting a case series of patients who firmly state that their condition of CTS arised or got worse during a typical presentation of COVID-19. The outbreak of COVID-19 has resulted in significant global healthcare implications. While the respiratory manifestations of COVID-19 have been widely studied, there is emerging evidence suggesting potential associations between COVID-19 and various other health conditions. This review of the literature aims to investigate the potential relationship between COVID-19 and the development or exacerbation of CTS. By synthesizing the available literature on this topic, we aim to provide a comprehensive overview of the current knowledge and enhance our understanding of the potential implications of COVID-19 on CTS. Case series: In this article we report 13 cases of typical presentations of COVID-19 with fever, myalgia, and respiratory system involvement, with a simultaneous aggravation of the median nerve pre-existing neuralgia and some cases that developed a median nerve neuralgia during COVID-19, which came to the attention of the hand surgeon. Some cases had stable symptomatic CTS and were on waiting list for surgical carpal tunnel release, some cases were previously asymptomatic and developed a median nerve neuralgia during COVID-19. All patients referred to a rapid worsening of acral paraesthesia and neuralgic pain of the same quality of CTS and in the median nerve topography. Some patients developed typical COVID-19 symptoms and died; the others were surgically treated. CTS could be an atypical presentations of COVID-19 or a condition of long-covid disease and clinical and epidemiological significance needs to be fully studied. We presented cases of worsening of the median nerve neuralgia which presented among other symptoms of COVID infection. We conclude a causal relation may exist and needs to be further investigated.

CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family.

MTG8 (HGMW-approved symbol CBFA2T1) was originally identified as one of the loci involved in the t(8;21)(q22;q22) of acute myeloid leukemia. We characterize two human MTG8-related genes, MTGR1 and MTGR2 (HGMW-approved symbols CBFA2T2 and CBFA2T3). The former is duplicated in mouse, one locus possibly being a retroposon. Multiple MTG8-related sequences are found in several vertebrate species, from fish to mammals, albeit not in a urodele. MTGR2 maps to 16q24 and, like MTG8 and MTGR1, is close to one of three loci encoding a syntrophin (dystrophin-associated proteins). Moreover, an alternative MTGR1 promoter/5' exon is contained within the alpha1-syntrophin locus. Thus, the two classes of genes may define novel paralogous groups. MTGR1 is expressed mainly in brain, while MTGR2 is expressed in the thymus and possibly in monocytes. Like MTG8, MTGR1 is transcribed into a number of isoforms due to alternative splicing of different 5' exons onto a common splice acceptor site. Comparison of the three predicted human MTG8-related polypeptides to their Drosophila counterpart (nervy) highlights four separate regions of sequence conservation that may correspond to distinct domains. The most NH2-terminal of these is proportionately more conserved among the human polypeptides, presumably due to specific structural/functional constraints.

Use of the Oximeter-539 WTW, equipped with a sensor Trioxmatic-300, for the functional analysis of dilute solutions of human Hb-A.

Dissociation curves for oxygen of dilute samples of human adult Hb-A were evaluated on this occasion, by using the Oximeter-539 WTW with its sensor, and a suitable spectrophotometer. At this purpose, Hb samples were desaturated in oxygen upon given experimental conditions, by bubbling pure nitrogen in them, and their re-oxigenation in air was followed, step by step, by multiple oximetries. In addition, all the spectrophotometric measurements of the saturation of Hb-O2%, corresponding to each individual oximetry, were carried out parallely but separately. Dilution of Hb-A was maintained at 0.1 mM in heme. The p50 at pH 7.3 was 4.435 +/- 0.299 Torr, with the n-value of 2.7 +/- 0.2; Bohr effect was -0.55 +/- 0.08, within a pH range between 6.8, 7.3 and 7.8, whereas chloride and DPG effects at pH 7.3 (the most useful value) were 0.42 +/- 0.44 and 0.453 +/- 0.0187 respectively. In conclusion, these results are similar to those obtained with automated procedures, upon comparable experimental conditions, but do not require expensive and sophisticated instruments. Such a technique could be very useful in the hemoglobinopathies, which are common in Italy, and it could be easily adapted to perform comparative studies on animal hemoglobins not far from human species.

The common TEL/AML1 rearrangement does not represent a frequent event in acute lymphoblastic leukaemia occuring in children with Down syndrome.

Individuals with constitutional trisomy 21 (Down syndrome) are at increased risk of developing acute leukaemias, both of myeloid and lymphoid lineage. Although the cause of leukaemia in Down syndrome (DS) remains unknown, potential candidate genes include the ones on chromosome 21, and in particular AML1, the rearrangement of which in the t(8,21) is associated with the French-American-British (FAB) classification M2 subtype of acute myeloid leukaemia (AML) in the general population and has been described in Down patients with AML-M2. Recently, a new rearrangement involving AML1, the t(12;21), producing the TEL/AML1 hybrid transcript, has been described by molecular analysis as the most recurrent genetic lesion in childhood acute lymphoblastic leukemia (ALL). In order to investigate whether the t(12;21) could give a molecular clue as to the precise basis of the etiologic association between DS and acute lymphoblastic leukemia, we tested a series of 11 consecutive cases of ALL in DS children for the presence of the TEL/AML1 transcript, by RT-PCR analysis. We report absence of the TEL/AML1 rearrangement among the 11 cases tested. This data may be suggestive of alternative pathways involved in the pathogenesis of ALL in children with constitutional trisomy 21.

Outcome and lineage involvement in t(12;21) childhood acute lymphoblastic leukaemia.

The t(12;21)(p13;q22) translocation has been described recently as the most recurrent genetic lesion in paediatric acute lymphoblastic leukaemias (ALLs). It has also been associated with B-precursor lineage involvement and good outcome. We tested 51 diagnostic paediatric ALLs and found 11 cases with molecular evidence of the t(12;21). Interestingly, amongst t(12;21) positive patients, we report three cases with hybrid phenotype, and two cases showing an aggressive and fatal disease. Our data show that the t(12;21) does not represent an independent good-risk indicator. Long follow-ups and additional molecular investigations are needed to assess the prognostic and pathogenetic relevance of t(12;21) in childhood ALLs.

Molecular events in chronic myeloid leukemia progression.

Chronic myelogenous leukemia presents two distinct clinical phases: the chronic phase is characterised by a marked expansion of the myeloid compartment which still retains a normal differentiative capacity, whereas a differentiation block is the clinical hallmark of the acute transformation. The molecular mechanism underlying the CML progression are still poorly understood. The occurrence of additional molecular lesions, involving the p53, the RAS and the p16 genes may complement and fulfil the BCR/ABL transforming potential, finally leading to an acute leukemic phenotype. However, several lines of evidence suggest that also quantitative changes of the BCR/ABL transcript amounts could explain the progression of the leukemic phenotype in the BCR/ABL-positive hematologic malignancies.

Molecular pathways in low grade B-cell lymphoma.

Low grade B-cell non-Hodgkin's lymphomas (B-NHL) represent a markedly heterogeneous group of lymphoproliferative disorders, including B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CCL/SLL), lymphoplasmacytoid lymphoma (LPL), follicular lymphoma (FL), mucosa-associated lymphoid tissue lymphoma (MALTL), and splenic lymphoma with villous lymphocytes (SLVL). The molecular pathogenesis of low grade B-NHL is characterized by distinct genetic pathways which selectively associate with each clinicopathologic category. At diagnosis, B-CLL/SLL frequently display deletions of 13q14 and trisomy 12, whereas evolution to Richter's syndrome associates with disruption of p53. LPL carries t(9;14)(p13;q32) in 40-50% of the cases, leading to the deregulated expression of the PAX-5 gene. FL consistently harbors rearrangements of BCL-2 independent of the cytologic variant. With time, a fraction of FL cases accumulates mutations of p53 and evolves into a high grade B-NHL. Low grade MALTL are characterized by the frequent occurrence of trisomy 3 and, occasionally, by p53 mutations. SLVL carries p53 mutations in a fraction of cases. The identification of distinct genetic categories among low grade B-NHL may help in the therapeutic stratification of these disorders. In addition, genetic lesions of low grade B-NHL have proved to be a useful molecular marker for monitoring minimal residual disease.

Neonatal calf diarrhea induced by rotavirus.

This presentation summarizes the results of a comprehensive study on rotaviruses isolated in Italy from calves and rabbits affected by neonatal diarrhea. The results clearly indicated that rotavirus infection is widespread and supported the evidence for an etiologic role of these viruses in neonatal diarrhea. The evidence of differences in virulence among bovine rotaviruses appeared also to be confirmed. Conventionally reared calves were fully susceptible to the experimental infection induced by three rotaviruses originating from heterologous hosts, i.e. monkeys, pigs and rabbits, respectively. When rotavirus strains of bovine, simian, porcine and rabbit origin were compared by cross neutralization tests, it was found the simian and porcine strains were indistinguishable and both appeared to relate antigenically to the bovine strain. On the other hand, a reciprocal antigenic correlation was found between bovine and rabbit isolates. Finally, it was proven that feeding newborn calves with colostrum of their dams, previously vaccinated with an inactivated rotavirus vaccine, could prevent the neonatal diarrhea from occurring.

Field trial evaluation of an inactivated rotavirus vaccine against neonatal diarrhea of calves.

Field trials were conducted using an inactivated rotavirus vaccine for prevention of calf neonatal diarrhea. For the trials, 458 pregnant cows from 26 herds were involved. In each herd, cows which had been inseminated within a period of two months were selected and randomly subdivided in two groups. Cows in one group (248 head in total) were vaccinated 6 weeks before calving and again 4 weeks later; cows in the other group (210 head in total) were left as unvaccinated controls. At calving, colostrum was collected from each cow and stored at -30 degrees C until used for feeding calves. The newborn calves, beginning the second day of life and for the next 7-10 consecutive days, each was fed a daily supplement of 400 ml of colostrum from its dam. The diarrhea occurred in 86 (40.9%) calves that had received colostrum from unvaccinated dams (normal colostrum), and in 7 (2.8%) calves which were fed colostrum from vaccinated dams (immune colostrum). The disease was very severe in the normal colostrum-fed calves and 52 of them died. Those calves which survived the disease underwent a significant loss of condition. By contrast, the 7 immune colostrum-fed calves displayed a rather mild enteric condition, and all recovered without any sequela being observed.

Reactivation in calves of latent infection by Bovid herpesvirus-4.

Nine calves, six of which had been infected with strain 85/BH 16TV and three with strain 85/BH 232TN of Bovid herpesvirus-4 (BHV-4), were treated with dexamethasone (DMS) three months after infection. DMS administration did not induce any clinical signs of disease, but BHV-4 was isolated from the nasal swabbings of all calves for a maximum of 8 days after the start of DMS treatment. The virus was also isolated from the nerve tissues, nasal mucosa, lymph nodes, lung and spleen of 4 calves that were killed at different stages (3, 5, 7 days) of the DMS treatment. Intranuclear inclusions associated with cellular shrinkage were found in the neural tissues of calves killed either 3 or 5 days after the start of DMS treatment. Unexpectedly, a latent infection by infectious bovine rhinotracheitis (IBR) virus was reactivated. The virus was isolated from the nasal swabbings of two calves and also from the brain, cerebellum and nasal mucosa of one calf killed 5 days after the start of DMS treatment.

Experimental infection of calves with strains of Bovid herpesvirus-4.

Fourteen calves were inoculated intranasally (i.n.) with the viral isolates as follows: 5 with 85/BH 16TV, 1 with 85/BH 17TV, 1 with 85/BH 18TV, 2 with 85/BH 231TN and 5 with 85/BH 232TN. Strain 85/BH 16TV was the only one which caused overt respiratory-like disease in all inoculated calves. Onset of the disease was observed after 7-8 days of incubation and was characterized by fever, depression, nasal discharge and coughing. Virus was isolated from the nasal swabbings of calves obtained from post-infection day (PID) 2-10. The other viral strains did not cause any sign of disease although virus was isolated regularly from the nasal swabbings of the inoculated calves. Virus was recovered from central nervous system tissues of calves that were infected with 85/BH 16TV or 85/BH 232TN strains and were killed on PID 4 or 8. Virus was also isolated from other tissues, such as lymph node, nasal mucosa (PID 8), or lung (PID 4). It was speculated that the nervous system could be one of the target areas of the virus of the naturally occurring infection by BHV-4. This might indicate a possible role of the nervous system (site of latency?) in the pathogenesis of BHV-4 as is the case in certain herpesviral infections of man and the lower animals.

A study of a herpesvirus isolated from dairy cattle with a history of reproductive disorders.

Three strains of herpesvirus were recovered from cows with vulvovaginitis. The three isolates (85/BH 16TV, 85/BH 17TV, 85/BH 18TV), when compared by cross serum neutralization (SN) tests, were found to be antigenically identical. They were serologically distinct from infectious bovine rhinotracheitis (IBR) virus and Bovid herpesvirus 2 (BHV2), while they cross reacted with bovine herpesvirus DN-599. Besides the serologic aspects, the three isolates appeared to share common biological, physical and morphological properties with the newly recognized bovine herpesviruses, of which DN-599 is a representative strain.

A comparison of rotavirus strains of bovine, simian and porcine origin.

Three rotavirus strains of bovine, simian and porcine origin, respectively, were compared. The 3 viruses induced a classic rotaviral infection in newborn, conventionally reared calves. The cross neutralization tests revealed an antigenic identity of simian and porcine rotaviruses and a slight serologic correlation of these two viruses with the bovine rotavirus strain. However, in reciprocal cross protection tests carried out in calves, the simian rotavirus antiserum afforded weak protection to challenge infection with either the porcine or the bovine viruses. By contrast, the protective level of the bovine and the porcine rotavirus antisera was relatively high. It was speculated that the 81/36F bovine rotavirus could be considered, tentatively, as an antigenic reassortant rotavirus strain.

Isolation and characterization of cytopathic strains of rotavirus from rabbits. Brief report.

Three cytopathic rotavirus isolates were recovered from young rabbits affected by an enteric syndrome. The three isolates, when compared by cross serum-neutralization tests, were found to be of the same serotype. Cross neutralization occurred also between a representative of the rabbit isolates and one strain of bovine rotavirus.

Response of calves previously inoculated with inactivated herpes simplex virus to challenge exposure with Bovid herpesvirus 2.

Concentrated antigen of Herpes simplex virus (HSV) types 1 and 2, previously inactivated with Triton 100X, were inoculated into calves. Thirty-two days later the calves were challenge exposed either by the intradermal or the intravenous route with Bovid herpesvirus 2 (BHV 2). The HSV-immune calves responded to BHV 2 infection with clinical signs which were much less severe that those observed in the challenge control calves. The skin lesions in the calves exposed to intravenous inoculation of BHV 2, were fewer in the calves in the HSV-immune group, whereas they were heavily disseminated, covering the skin of the entire body, in the control calves. In the case of calves which received BHV 2 intradermally, the titer of the virus underwent a reduction of more than one log unit in the pre-immunized calves. The most significant serologic finding was that the HSV-preimmunized calves produced antibody to the BHV 2 challenge virus at an earlier time than did the control calves. The immunologic relationship between BHV 2 and HSV was confirmed by the results of this study.

Comparative studies of strains of infectious bovine rhinotracheitis virus isolated from latently infected calves.

Three strains (479 C, 778 TL, 982 LE) of infectious bovine rhinotracheitis (IBR) virus isolated from latently infected calves were compared with the prototype strain of IBR virus (LA strain) in studies which included restriction endonuclease analysis, experimental infection, and reciprocal cross protection tests in cattle. From the restriction endonuclease analysis it appeared that the 3 "latent" viruses were derived from the same isolate, and that it differed slightly from the LA strain. However, latency does not seem to have affected the pathogenicity or the immunogenicity of the virus. This is demonstrated by the identical clinical and virologic response of calves subjected to experimental infection with the various strains under study, and by the finding that when the LA strain and a "latent" strain (982 LE) were tested in cross protection tests in cattle, they proved to be mutually protective.

The efficacy of colostrum from cows vaccinated with rotavirus in protecting calves to experimentally induced rotavirus infection.

Calves which were continuously fed colostrum from vaccinated cows for the first ten days of life, were fully refractory to experimental infection with strain 81/36 F of bovine rotavirus. By contrast, the response to virus exposure of calves which were treated with normal colostrum was identical to that of the control calves, in that they underwent severe diarrhea and a significant slowing of the growth rate. The antibody titer in the milk of vaccinated cows tends to decline rapidly so that it no longer provides any protective effect. Two alternatives were considered feasible in improving prophylaxis for rotavirus infections: (a) the continuous feeding of calves with 1st day colostrum as part of the ration throughout the period of greatest risk (first week of life), or (b) enhancing the efficacy of the vaccine in pregnant cows to the point where antibody concentration in the milk would remain at a protective level.