Background COVID-19 restrictions have significantly limited access to in-person educational and healthcare services for all, including individuals with intellectual and developmental disabilities (IDDs). The objectives of this online survey that included both national and international families were to capture changes in access to healthcare and educational services for individuals with IDDs that occurred shortly after restrictions were initiated and to survey families on resources that could improve services for these individuals. Methods This was an online survey for caregivers of individuals with (1) a genetic diagnosis and (2) a neurodevelopmental diagnosis, including developmental delay, intellectual disability, autism spectrum disorder or epilepsy. The survey assessed (1) demographics, (2) changes in access to educational and healthcare services and (3) available and preferred resources to help families navigate the changes in service allocation. Results Of the 818 responses (669 within the USA and 149 outside of the USA), most families reported a loss of at least some educational or healthcare services. Seventy-four per cent of parents reported that their child lost access to at least one therapy or education service, and 36% of respondents lost access to a healthcare provider. Only 56% reported that their child received at least some continued services through tele-education. Those that needed to access healthcare providers did so primarily through telemedicine. Telehealth (both tele-education and telemedicine) was reported to be helpful when available, and caregivers most often endorsed a need for an augmentation of these remote delivery services, such as 1:1 videoconference sessions, as well as increased access to 1:1 aides in the home. Conclusions COVID-19 restrictions have greatly affected access to services for individuals with syndromic IDDs. Telehealth may provide opportunities for delivery of care and education in a sustainable way, not only as restrictions endure but also after they have been lifted.

Overexpression of anti-apoptotic Bcl-2 family proteins may play an important role in the aggressive behavior of prostate cancer cells and their resistance to therapy. The Bcl-2 homology 3 domain (BH3) is a uniquely important functional element within the pro-apoptotic class of the Bcl-2-related proteins, mediating their ability to dimerize with other Bcl-2-related proteins and promote apoptosis. The BH3 inhibitors (BH3Is) function by disrupting the interactions mediated by the BH3 domain between pro- and anti-apoptotic members of the Bcl-2 family and liberating more Bax/Bak to induce mitochondrial membrane permeabilization. LNCaP-derived C4-2 human prostate cancer cells are quite resistant to non-tagged, human recombinant soluble Apo2 ligand [Apo2L, also Tumor necrosis factor (TNF)-related apoptosis-inducing ligand, TRAIL], a tumor specific drug that is now in clinical trials. However, when Apo2L/TRAIL was combined with the Bcl-xL inhibitor, BH3I-2', it induced apoptosis synergistically through activation of Caspase-8 and the proapoptotic Bcl-2 family member Bid, resulting in the activation of effector Caspase-3 and proteolytic cleavage of Poly(ADP-ribose) polymerase, events that were blocked by the pan-caspase inhibitor zVAD-fmk. Our data indicate that, in combination with the BH3 mimetic, BH3I-2', Apo2L/TRAIL synergistically induces apoptosis in C4-2 human prostate cancer cells through both the extrinsic and intrinsic apoptotic pathways.

Background On 16 Jan 2021, India launched its immunization program against COVID-19. Among the first recipients were 1.59 million Health Care Workers (HCWs) and Frontline Workers (FLWs) of the Indian Armed Forces, who were administered COVISHIELD (Astra Zeneca). We present an interim analysis of vaccine effectiveness (VE) estimates till 30 May 2021. Methods The VIN-WIN cohort study was carried out on anonymized data of HCWs and FLWs of Indian Armed Forces. The existing surveillance system, enhanced for COVID-19 monitoring, was sourced for data. The cohort transitioned from Unvaccinated (UV) to Partially Vaccinated (PV) to Fully Vaccinated (FV), serving as its own internal comparison. Outcomes studied in the three groups were breakthrough infections and COVID related deaths. Incidence Rate Ratio (IRR) was used to compare outcomes among the three groups to estimate VE. Results Data of 1,595,630 individuals (mean age 27.6 years; 99% male) over 135 days was analysed. Till 30 May 21, 95.4% and 82.2% were partially and fully vaccinated. The UV, PV and FV compartments comprised 106.6, 46.7 and 58.7 million person-days respectively. The number of breakthrough cases in the UV, PV and FV groups were 10061, 1159 and 2512; while the deaths were 37, 16 and 7 respectively. Corrected VE was 91.8–94.9% against infections. Conclusion Interim results of the VIN-WIN cohort study of 1.59 million HCWs and FLWs of Indian Armed Forces showed a ∼93% reduction in COVID-19 breakthrough infections with COVISHIELD vaccination.

The prevalence rate of low back pain in a number of studies ranged from 22% to 65% in one year, and lifetime prevalence ranged from 11% to 84%. Over the years many percutaneous minimally invasive therapeutic modalities have evolved. Intradiscal oxygen-ozone therapy has also showed promising results. We undertook a prospective cohort study to evaluate the therapeutic outcome of oxygen-ozone therapy on patients with lumber disc herniation in the Indian population. After obtaining ethical committee and investigational review board permission, 53 consecutive patients complying with selection criteria were treated with a single session of oxygen-ozone therapy. All presented with clinical signs of lumber nerve root compression supported by CT and MRI findings. All patients received 3–7 ml of ozone-oxygen mixture at an ozone concentration of 29–32 mc/ml of oxygen. Therapeutic outcome was assessed after three weeks, three months, six months, one year and two years on a visual analog scale and Oswestry low back pain disability questionnaire. Pain intensity was significantly reduced following treatment (VAS baseline 7.58 ± 0.86, after three weeks 2.75 ± 1.42 and after two years 2.64 ± 2.14). Similarly the Oswestry disability index showed a remarkable improvement in the functional status of the patients (p<0.05). No major complication was observed in this case series. Oxygen-ozone treatment is highly effective in relieving low back pain due to lumber disc herniation.

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Objectives: Noxious stimuli activate small to medium-sized dorsal root ganglion (DRG) neurons. Intense noxious stimuli result in the release of substance P (SP) from the central terminals of these neurons. It binds to the neurokinin type 1 receptor (NK1r) and sensitises the dorsal horn neurons. SP is also released from the peripheral terminals leading to neurogenic inflammation. However, their individual contribution at spinal and peripheral levels to postincisional nociception has not been delineated as yet. Methods: Sprague-Dawley rats were administered different doses (3-100 μg) of an NK1r antagonist (L760735) by intrathecal (i.t.) route before hind paw incision. On the basis of its antinociceptive effect on guarding behaviour, the 30 μg dose was selected for further study. In different sets of animals, this was administered i.t. (postemptive) and intrawound (i.w.). Finally, in another group, drug (30 μg) was administered through both i.t and i.w. routes. The antinociceptive effect was assessed and compared. Expression of SP was examined in the spinal cord. Intrawound concentration of SP and inflammatory mediators was also evaluated. Results: Postemptive i.t. administration significantly attenuated guarding and allodynia. Guarding was alone decreased after i.w. drug treatment. Combined drug administration further attenuated all nociceptive parameters, more so after postemptive treatment. Expression of SP in the spinal cord decreased post incision but increased in the paw tissue. Inflammatory mediators like the nerve growth factor also increased after incision. Conclusion: In conclusion, SP acting through the NK1r appears to be an important mediator of nociception, more so at the spinal level. These findings could have clinical relevance.

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Apo2 Ligand or Tumour Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (Apo2L/ TRAIL) is a member of the TNF gene superfamily that selectively induces apoptosis in tumor cells of diverse origins through engagement of death receptors. We have recently demonstrated that Type I interferons (IFN-α and β) induce apoptosis in multiple myeloma (MM) cell lines and in plasma cells from MM patients. Moreover, Apo2L selectively induces apoptosis of patient MM tumor cells while sparing non-malignant cells. Apo2L induction is one of the earliest events following IFN administration in these cells. IFNs activate Caspases and the mitochondrial-dependent apoptotic pathway mediated by Apo2L production. Cell death induced by IFNs and Apo2L can be blocked by a dominant-negative Apo2L receptor, DR5, and is regulated by members of the Bcl-2 family of proteins. This review is focused on the apoptotic signaling pathways regulated by Apo2L and Bcl-2-family proteins and summarizes what is known about their clinical role.